Trilaciclib dihydrochloride

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H30N8O.2ClH
Molecular Weight	519.47
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of Trilaciclib dihydrochloride

Structure Search

SMILES

Cl.Cl.CN1CCN(CC1)C2=CN=C(NC3=NC4=C(C=C5N4C6(CCCCC6)CNC5=O)C=N3)C=C2

InChI

InChIKey=BRCYOXKEDFAUSA-UHFFFAOYSA-N

InChI=1S/C24H30N8O.2ClH/c1-30-9-11-31(12-10-30)18-5-6-20(25-15-18)28-23-26-14-17-13-19-22(33)27-16-24(7-3-2-4-8-24)32(19)21(17)29-23;;/h5-6,13-15H,2-4,7-12,16H2,1H3,(H,27,33)(H,25,26,28,29);2*1H

HIDE SMILES / InChI

Molecular Formula	C24H30N8O
Molecular Weight	446.548
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://pubmed.ncbi.nlm.nih.gov/33861388|https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214200s000lbl.pdf

Trilaciclib (Cosela™) is a small-molecule, short-acting, inhibitor of cyclin-dependent kinases (CDK) 4 and 6 developed by G1 Therapeutics for its myeloprotection and potential antitumor efficacy and safety benefits in combination with cancer chemotherapy. CDKs govern cell cycle progression, and trilaciclib induces a transient, reversible G1 cell cycle arrest of proliferating haematopoietic stem and progenitor cells in bone marrow, thus protecting them from damage during chemotherapy. In February 2021, trilaciclib received its first approval in the USA to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer (ES-SCLC). Clinical studies in breast cancer, colorectal cancer and small cell lung cancer are underway in several countries.

Approval Year

Targets

Primary Target	Pharmacology	Potency
Cyclin-dependent kinase 6 16 Target ID: CHEMBL2508 Sources: https://pubmed.ncbi.nlm.nih.gov/26826116\|https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214200s000lbl.pdf	Inhibitor 8504	4.0 nM [IC50]
Cyclin-dependent kinase 4 26 Target ID: CHEMBL331 Sources: https://pubmed.ncbi.nlm.nih.gov/26826116\|https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214200s000lbl.pdf	Inhibitor 8504	1.0 nM [IC50]
Cyclin-dependent kinase 9 24 Target ID: CHEMBL3116 Sources: https://pubmed.ncbi.nlm.nih.gov/26826116\|https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214200s000lbl.pdf	Inhibitor 8504	0.05 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Extensive-stage small cell lung cancer 4 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214200s000lbl.pdf	Secondary		Approved 8583	COSELA Approved Use Indicated to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer. Launch Date 2021

C_max

Value	Dose	Co-administered	Analyte	Population
1270 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=11	240 mg/m² single, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
1220 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=12	240 mg/m² 1 times / day steady-state, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered:		TRILACICLIB plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
2457 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=24	240 mg/m² single, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1020 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=24	240 mg/m² single, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
50.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	6 mg/m² single, intravenous dose: 6 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
119 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	12 mg/m² single, intravenous dose: 12 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
255 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	24 mg/m² single, intravenous dose: 24 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
224 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	49 mg/m² single, intravenous dose: 49 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
910 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	96 mg/m² single, intravenous dose: 96 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
910 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	96 mg/m² single, intravenous dose: 96 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1969 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	192 mg/m² single, intravenous dose: 192 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1240 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	200 mg/m² single, intravenous dose: 200 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: CARBOPLATIN	CARBOPLATIN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1620 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	200 mg/m² 1 times / day multiple, intravenous dose: 200 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: CARBOPLATIN	CARBOPLATIN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1570 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	240 mg/m² single, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: CARBOPLATIN	CARBOPLATIN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2260 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	240 mg/m² 1 times / day multiple, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: CARBOPLATIN	CARBOPLATIN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1200 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	200 mg/m² single, intravenous dose: 200 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: TOPOTECAN	TOPOTECAN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1060 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=10	200 mg/m² 1 times / day multiple, intravenous dose: 200 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: TOPOTECAN	TOPOTECAN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1270 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=10	240 mg/m² single, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: TOPOTECAN	TOPOTECAN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1220 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=10	240 mg/m² 1 times / day multiple, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: TOPOTECAN	TOPOTECAN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1110 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=10	280 mg/m² single, intravenous dose: 280 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: TOPOTECAN	TOPOTECAN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2220 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=10	280 mg/m² 1 times / day multiple, intravenous dose: 280 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: TOPOTECAN	TOPOTECAN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1570 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/	240 mg/m² single, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
2730 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=11	240 mg/m² single, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
2890 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=12	240 mg/m² 1 times / day steady-state, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered:		TRILACICLIB plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
3922 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=24	240 mg/m² single, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2969 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=24	240 mg/m² single, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
66.6 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	6 mg/m² single, intravenous dose: 6 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
143 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	12 mg/m² single, intravenous dose: 12 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
279 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	24 mg/m² single, intravenous dose: 24 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
518 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	49 mg/m² single, intravenous dose: 49 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1341 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	96 mg/m² single, intravenous dose: 96 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1341 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	96 mg/m² single, intravenous dose: 96 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3106 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	192 mg/m² single, intravenous dose: 192 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2560 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	200 mg/m² single, intravenous dose: 200 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: CARBOPLATIN	CARBOPLATIN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3110 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	200 mg/m² 1 times / day multiple, intravenous dose: 200 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: CARBOPLATIN	CARBOPLATIN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2280 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	240 mg/m² single, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: CARBOPLATIN	CARBOPLATIN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2960 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	240 mg/m² 1 times / day multiple, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: CARBOPLATIN	CARBOPLATIN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2410 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	200 mg/m² single, intravenous dose: 200 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: TOPOTECAN	TOPOTECAN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2320 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=10	200 mg/m² 1 times / day multiple, intravenous dose: 200 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: TOPOTECAN	TOPOTECAN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2910 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=10	240 mg/m² single, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: TOPOTECAN	TOPOTECAN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2880 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=10	240 mg/m² 1 times / day multiple, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: TOPOTECAN	TOPOTECAN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3490 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=10	280 mg/m² single, intravenous dose: 280 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: TOPOTECAN	TOPOTECAN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4520 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=10	280 mg/m² 1 times / day multiple, intravenous dose: 280 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: TOPOTECAN	TOPOTECAN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2279.98 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/	240 mg/m² single, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
14 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=7	single, intravenous		TRILACICLIB plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
5.32 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	6 mg/m² single, intravenous dose: 6 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7.62 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	12 mg/m² single, intravenous dose: 12 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
9.28 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	24 mg/m² single, intravenous dose: 24 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
12.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	49 mg/m² single, intravenous dose: 49 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
14.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	96 mg/m² single, intravenous dose: 96 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
14.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	96 mg/m² single, intravenous dose: 96 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
14.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	192 mg/m² single, intravenous dose: 192 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7.87 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	200 mg/m² single, intravenous dose: 200 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: CARBOPLATIN	CARBOPLATIN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
9.12 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	200 mg/m² 1 times / day multiple, intravenous dose: 200 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: CARBOPLATIN	CARBOPLATIN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.91 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	240 mg/m² single, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: CARBOPLATIN	CARBOPLATIN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
4.03 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	240 mg/m² 1 times / day multiple, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: CARBOPLATIN	CARBOPLATIN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
6.92 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=9	200 mg/m² single, intravenous dose: 200 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: TOPOTECAN	TOPOTECAN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8.57 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=10	200 mg/m² 1 times / day multiple, intravenous dose: 200 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: TOPOTECAN	TOPOTECAN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6.79 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=10	240 mg/m² single, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: TOPOTECAN	TOPOTECAN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8.09 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=10	240 mg/m² 1 times / day multiple, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: TOPOTECAN	TOPOTECAN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7.38 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=10	280 mg/m² single, intravenous dose: 280 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: TOPOTECAN	TOPOTECAN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8.54 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/ \| https://static-content.springer.com/esm/art%3A10.1007%2Fs00280-021-04239-9/MediaObjects/280_2021_4239_MOESM1_ESM.pdf#page=10	280 mg/m² 1 times / day multiple, intravenous dose: 280 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: TOPOTECAN	TOPOTECAN	TRILACICLIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.91 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33595690/	240 mg/m² single, intravenous dose: 240 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		TRILACICLIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
28.3% OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000PharmR.pdf#page=35			TRILACICLIB plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
240 mg/m2 1 times / day multiple, intravenous Recommended Dose: 240 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 240 mg/m2, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000StatR.pdf https://clinicaltrials.gov/ct2/show/NCT02514447?term=G1T28-03&draw=2&rank=1	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000StatR.pdf https://clinicaltrials.gov/ct2/show/NCT02514447?term=G1T28-03&draw=2&rank=1	Disc. AE: Adverse event... AEs leading to discontinuation/dose reduction: Adverse event (4 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000StatR.pdf https://clinicaltrials.gov/ct2/show/NCT02514447?term=G1T28-03&draw=2&rank=1
240 mg/m2 1 times / day Recommended Dose: 240 mg/m2, 1 times / day Dose: 240 mg/m2, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000StatR.pdf https://clinicaltrials.gov/ct2/show/NCT02514447?term=G1T28-03&draw=2&rank=1	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000StatR.pdf https://clinicaltrials.gov/ct2/show/NCT02514447?term=G1T28-03&draw=2&rank=1	Disc. AE: Adverse event... AEs leading to discontinuation/dose reduction: Adverse event (6 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000StatR.pdf https://clinicaltrials.gov/ct2/show/NCT02514447?term=G1T28-03&draw=2&rank=1
240 mg/m2 3 times / day intramuscular Recommended Dose: 240 mg/m2, 3 times / day Route: intramuscular Dose: 240 mg/m2, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000StatR.pdf https://clinicaltrials.gov/ct2/show/NCT03041311?term=G1T28-05&draw=2&rank=1	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000StatR.pdf https://clinicaltrials.gov/ct2/show/NCT03041311?term=G1T28-05&draw=2&rank=1	Disc. AE: Adverse event... AEs leading to discontinuation/dose reduction: Adverse event (4 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000StatR.pdf https://clinicaltrials.gov/ct2/show/NCT03041311?term=G1T28-05&draw=2&rank=1
240 mg/m2 1 times / day multiple, intravenous Recommended Dose: 240 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 240 mg/m2, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000StatR.pdf https://clinicaltrials.gov/ct2/show/NCT02499770?term=G1T28-02&draw=2&rank=1	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000StatR.pdf https://clinicaltrials.gov/ct2/show/NCT02499770?term=G1T28-02&draw=2&rank=1	Other AEs: Adverse event... Other AEs: Adverse event Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000StatR.pdf https://clinicaltrials.gov/ct2/show/NCT02499770?term=G1T28-02&draw=2&rank=1

AEs

AE	Significance	Dose	Population
Adverse event	4 patients Disc. AE	240 mg/m2 1 times / day multiple, intravenous Recommended Dose: 240 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 240 mg/m2, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000StatR.pdf https://clinicaltrials.gov/ct2/show/NCT02514447?term=G1T28-03&draw=2&rank=1	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000StatR.pdf https://clinicaltrials.gov/ct2/show/NCT02514447?term=G1T28-03&draw=2&rank=1
Adverse event	6 patients Disc. AE	240 mg/m2 1 times / day Recommended Dose: 240 mg/m2, 1 times / day Dose: 240 mg/m2, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000StatR.pdf https://clinicaltrials.gov/ct2/show/NCT02514447?term=G1T28-03&draw=2&rank=1	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000StatR.pdf https://clinicaltrials.gov/ct2/show/NCT02514447?term=G1T28-03&draw=2&rank=1
Adverse event	4 patients Disc. AE	240 mg/m2 3 times / day intramuscular Recommended Dose: 240 mg/m2, 3 times / day Route: intramuscular Dose: 240 mg/m2, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000StatR.pdf https://clinicaltrials.gov/ct2/show/NCT03041311?term=G1T28-05&draw=2&rank=1	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000StatR.pdf https://clinicaltrials.gov/ct2/show/NCT03041311?term=G1T28-05&draw=2&rank=1
Adverse event		240 mg/m2 1 times / day multiple, intravenous Recommended Dose: 240 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 240 mg/m2, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000StatR.pdf https://clinicaltrials.gov/ct2/show/NCT02499770?term=G1T28-02&draw=2&rank=1	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000StatR.pdf https://clinicaltrials.gov/ct2/show/NCT02499770?term=G1T28-02&draw=2&rank=1

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1087 inhibitor 2252 substrate 1946	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT1 725 OAT3 747 OATP1B3 961 CYP1A2 2153 CYP2B6 926 CYP2C8 1057 CYP2C19 2057 MATE2-K 77 MATE1 415 BCRP 910 OCT2 779 BSEP 550 P-gp 1741 OATP1B1 1079	MATE1 182 MATE2-K 33 P-gp 2052 BCRP 697 BSEP 63 OATP1B1 503 OATP1B3 435 OCT2 434	CYP1A2 832 CYP2B6 669

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=25 Page: 9 \| 25	no
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=25 Page: 9 \| 25	no
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=25 Page: 9 \| 25	no
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=25 Page: 9 \| 25	no
MATE2-K 77	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=8 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=26 Page: 9 \| 8 \| 25 \| 26	yes [IC50 0.071 uM]	yes (co-administration study) Comment: Multiple doses of trilaciclib (240 mg/m2 once daily for 6 days) increased metformin AUCinf and Cmax by approximately 65% and 81% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=8 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=26 Page: 9 \| 8 \| 25 \| 26
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=8 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=26 Page: 9 \| 8 \| 25 \| 26	yes [IC50 0.152 uM]	yes (co-administration study) Comment: Multiple doses of trilaciclib (240 mg/m2 once daily for 6 days) increased metformin AUCinf and Cmax by approximately 65% and 81% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=8 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=26 Page: 9 \| 8 \| 25 \| 26
MATE1 416	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=8 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=26 Page: 9 \| 8 \| 25 \| 26	yes [IC50 0.175 uM]	yes (co-administration study) Comment: Multiple doses of trilaciclib (240 mg/m2 once daily for 6 days) increased metformin AUCinf and Cmax by approximately 65% and 81% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=8 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=26 Page: 9 \| 8 \| 25 \| 26
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=25 Page: 25.0	yes [IC50 0.6 uM]
BSEP 554	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=25 Page: 25.0	yes [IC50 10.8 uM]
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=25 Page: 9.0	yes [IC50 22.9 uM]
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=25 Page: 9 \| 25	yes [IC50 31.1 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=8 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=24 Page: 9 \| 8 \| 24	yes [IC50 36.4 uM]	no (co-administration study) Comment: Multiple doses of trilaciclib (240 mg/m2 once daily for 6 days) increased midazolam AUCinf by approximately 7% and decreased Cmax by approximately 17% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=8 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=24 Page: 9 \| 8 \| 24
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=24 Page: 9 \| 24	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
BSEP 63	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
MATE1 182	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
MATE2-K 33	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
OATP1B1 503	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=13 Page: 13.0	no
OATP1B3 435	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=13 Page: 13.0	no
OCT2 434	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=27 Page: 27.0	no	no (co-administration study) Comment: Cmax and AUCinf of trilaciclib were decreased by 19.9% and 17.3% by rifampicin (10-day multiple dosing) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=27 Page: 27.0
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	yes
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000PharmR.pdf#page=9 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214200Orig1s000PharmR.pdf#page=33 Page: 9 \| 33

PubMed

Title	Date	PubMed
Trilaciclib Prior to Chemotherapy in Patients with Metastatic Triple-Negative Breast Cancer: Final Efficacy and Subgroup Analysis from a Randomized Phase II Study.	2022-02-15	34887261
Trilaciclib prior to chemotherapy reduces the usage of supportive care interventions for chemotherapy-induced myelosuppression in patients with small cell lung cancer: Pooled analysis of three randomized phase 2 trials.	2021-09	34405547
Trilaciclib prior to chemotherapy and atezolizumab in patients with newly diagnosed extensive-stage small cell lung cancer: A multicentre, randomised, double-blind, placebo-controlled Phase II trial.	2021-05-15	33348420
Trilaciclib: First Approval.	2021-05	33861388

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose of COSELA is 240 mg/m2 as a 30-minute intravenous infusion completed within 4 hours prior to the start of chemotherapy on each day chemotherapy is administered.

Route of Administration: Intravenous

In Vitro Use Guide

Trilaciclib inhibits CDK4/cyclin D1 and CDK6/cyclin D3 with IC50 of 1 nM and 4 nM, respectively.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 23:28:02 GMT 2025` Edited by `admin` on `Mon Mar 31 23:28:02 GMT 2025`
Record UNII	4BX07W725T
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

Trilaciclib dihydrochloride

Common Name

English

COSELA

Preferred Name

English

SPIRO(CYCLOHEXANE-1,9'(6'H)-PYRAZINO(1',2':1,5)PYRROLO(2,3-D)PYRIMIDIN)-6'-ONE, 7',8'-DIHYDRO-2'-((5-(4-METHYL-1-PIPERAZINYL)-2-PYRIDINYL)AMINO)-, HYDROCHLORIDE (1:2)

Systematic Name

English

2'-((5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-2-YL)AMINO)-7',8'-DIHYDRO-6'HSPIRO(CYCLOHEXANE-1,9'-PYRAZINO(1',2':1,5)PYRROLO(2,3-D)PYRIMIDIN)-6'-ONE DIHYDROCHLORIDE

Systematic Name

English

TRILACICLIB DIHYDROCHLORIDE [ORANGE BOOK]

Common Name

English

G1T28 DIHYDROCHLORIDE

Code

English

Trilaciclib dihydrochloride [WHO-DD]

Common Name

English

Code System Code Type Description

CAS

1374635-07-0