LAROTRECTINIB SULFATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H22F2N6O2.H2O4S
Molecular Weight	526.514
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OS(O)(=O)=O.O[C@H]1CCN(C1)C(=O)NC2=C3N=C(C=CN3N=C2)N4CCC[C@@H]4C5=C(F)C=CC(F)=C5

InChI

InChIKey=PXHANKVTFWSDSG-QLOBERJESA-N

InChI=1S/C21H22F2N6O2.H2O4S/c22-13-3-4-16(23)15(10-13)18-2-1-7-28(18)19-6-9-29-20(26-19)17(11-24-29)25-21(31)27-8-5-14(30)12-27;1-5(2,3)4/h3-4,6,9-11,14,18,30H,1-2,5,7-8,12H2,(H,25,31);(H2,1,2,3,4)/t14-,18+;/m0./s1

HIDE SMILES / InChI

Molecular Formula	C21H22F2N6O2
Molecular Weight	428.4352
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	H2O4S
Molecular Weight	98.078
Charge	0
Count

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

Description
Sources: https://clinicaltrials.gov/ct2/show/NCT02576431 | https://clinicaltrials.gov/ct2/show/NCT02637687 | https://www.ncbi.nlm.nih.gov/pubmed/26216294

Larotrectinib (previously known as ARRY-470 and LOXO-101) is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities involving the tropomyosin receptor kinases (TRKs). Larotrectinib is in phase II clinical trials for the treatment patients with solid tumors, non-Hodgkin lymphoma and for the pediatric patients with advanced solid or primary CNS tumors.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Neurotrophic tyrosine kinase receptor 5 Target ID: CHEMBL3559684 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/26216294	Inhibitor 8297
Nerve growth factor receptor Trk-A 15 Target ID: CHEMBL2815 Sources: https://www.loxooncology.com/docs/presentations/LOXO101_EORTC2014_Poster.pdf	Inhibitor 8297	20.0 nM [IC50]
Neurotrophic tyrosine kinase receptor type 2 14 Target ID: CHEMBL4898 Sources: https://www.loxooncology.com/docs/presentations/LOXO101_EORTC2014_Poster.pdf	Inhibitor 8297	20.0 nM [IC50]
NT-3 growth factor receptor 9 Target ID: CHEMBL5608 Sources: https://www.loxooncology.com/docs/presentations/LOXO101_EORTC2014_Poster.pdf	Inhibitor 8297	20.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Solid tumors 145 Sources: https://clinicaltrials.gov/ct2/show/NCT02576431	Primary	Approved 8429	VITRAKVI Approved Use Vitrakvi is specifically indicated for the treatment of adult and pediatric patients with solid tumors that: • have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation, • are metastatic or where surgical resection is likely to result in severe morbidity, and • have no satisfactory alternative treatments or that have progressed following treatment. Launch Date 2018
Central nervous system neoplasms 4 Sources: https://clinicaltrials.gov/ct2/show/NCT02637687	Primary	Phase II 1132	Unknown Approved Use Unknown
Non-Hodgkin's lymphoma 79 Sources: https://clinicaltrials.gov/ct2/show/NCT03213704	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
788 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211710s000lbl.pdf	100 mg 2 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		LAROTRECTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
4351 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211710s000lbl.pdf	100 mg 2 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		LAROTRECTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.9 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211710s000lbl.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		LAROTRECTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf Page: 6.1	unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf Page: 6.1	Disc. AE: Brain edema, Intestinal perforation... Other AEs: Fatigue, Nausea... AEs leading to discontinuation/dose reduction: Brain edema (1 - 2) Intestinal perforation (1 - 2) Pericardial effusion (1 - 2) Pleural effusion (1 - 2) Small intestinal obstruction (1 - 2) Dehydration (1 - 2) Fatigue (1 - 2) ALT increased (1 - 2) AST increased (1 - 2) Enterocutaneous fistula (1 - 2) Amylase increased (1 - 2) Lipase increased (1 - 2) Muscular weakness (1 - 2) Abdominal pain (1 - 2) Asthenia (1 - 2) Decreased appetite (1 - 2) Dyspnea (1 - 2) Hyponatremia (1 - 2) Jaundice (1 - 2) Syncope (1 - 2) Vomiting (1 - 2) Nausea (1 - 2) Acute myeloid leukemia (1 - 2) Other AEs: Fatigue (>20) Nausea (>20) Dizziness (>20) Vomiting (>20) Anemia (>20) AST increased (>20) Cough (>20) ALT increased (>20) Constipation (>20) Diarrhea (>20) ALT increased (6%) AST increased (6%) Dizziness (3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf Page: 6.1
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf Page: Table 2	unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf Page: Table 2	Other AEs: Fatigue, Pyrexia... Other AEs: Fatigue (all grades, 37%) Pyrexia (all grades, 18%) Edema peripheral (all grades, 15%) Nausea (all grades, 29%) Vomiting (all grades, 26%) Constipation (all grades, 23%) Diarrhea (all grades, 22%) Abdominal pain (all grades, 13%) Dizziness (all grades, 28%) Headache (all grades, 14%) Cough (all grades, 26%) Dyspnea (all grades, 18%) Nasal congestion (all grades, 10%) Fatigue (grade 3-4, 3%) Pyrexia (grade 3-4, 1%) Nausea (grade 3-4, 1%) Vomiting (grade 3-4, 1%) Constipation (grade 3-4, 1%) Diarrhea (grade 3-4, 2%) Abdominal pain (grade 3-4, 2%) Dizziness (grade 3-4, 1%) Dyspnea (grade 3-4, 2%) Weight increased (all grades, 15%) Arthralgia (all grades, 14%) Myalgia (all grades, 14%) Muscular weakness (all grades, 13%) Back pain (all grades, 12%) Pain in extremity (all grades, 12%) Decreased appetite (all grades, 13%) Decreased appetite (all grades, 11%) Weight increased (grade 3-4, 4%) Arthralgia (grade 3-4, 1%) Myalgia (grade 3-4, 1%) Back pain (grade 3-4, 1%) Pain in extremity (grade 3-4, 1%) Decreased appetite (grade 3-4, 2%) Decreased appetite (grade 3-4, 2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf Page: Table 2
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf Page: Table 3	unhealthy, 28 - 82 years n = 176 Health Status: unhealthy Condition: solid tumor Age Group: 28 - 82 years Sex: M+F Population Size: 176 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf Page: Table 3	Other AEs: ALT increased, AST increased... Other AEs: ALT increased (all grades, 45%) AST increased (all grades, 45%) Hypoalbuminemia (all grades, 35%) Alkaline phosphatase increased (all grades, 30%) Anemia (all grades, 42%) Neutropenia (all grades, 23%) ALT increased (grade 3-4, 3%) AST increased (grade 3-4, 3%) Hypoalbuminemia (grade 3-4, 2%) Alkaline phosphatase increased (grade 3-4, 3%) Anemia (grade 3-4, 10%) Neutropenia (grade 3-4, 7%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210861s000lbl.pdf Page: Table 3
150 mg 2 times / day steady, oral Higher than recommended Dose: 150 mg, 2 times / day Route: oral Route: steady Dose: 150 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30624546/	unhealthy, adult n = 7 Health Status: unhealthy Condition: solid tumours Age Group: adult Sex: unknown Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/30624546/	DLT: Alanine aminotransferase increased, Aspartate aminotransferase increased... Dose limiting toxicities: Alanine aminotransferase increased (1 patient) Aspartate aminotransferase increased (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/30624546/
200 mg 2 times / day steady, oral Highest studied dose Dose: 200 mg, 2 times / day Route: oral Route: steady Dose: 200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30624546/	unhealthy, adult n = 6 Health Status: unhealthy Condition: solid tumours Age Group: adult Sex: unknown Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/30624546/	DLT: Dizziness... Dose limiting toxicities: Dizziness (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/30624546/
200 mg 2 times / day steady, oral Highest studied dose Dose: 200 mg, 2 times / day Route: oral Route: steady Dose: 200 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 91	unhealthy, adult n = 6 Health Status: unhealthy Condition: solid tumor Age Group: adult Sex: unknown Population Size: 6 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 91	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 91
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30624546/	unhealthy, adult n = 6 Health Status: unhealthy Condition: solid tumours Age Group: adult Sex: unknown Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/30624546/	DLT: Dizziness... Dose limiting toxicities: Dizziness (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/30624546/

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781 inhibitor 1587 substrate 1737	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 699 BSEP 402 CYP1A2 1524 CYP2B6 810 CYP2C19 1478 CYP2C8 911 MATE1 306 MATE2 263 OAT1 599 OAT3 642 OATP1B1 788 OATP1B3 706 OCT1 512 OCT2 647 P-gp 1461	BCRP 561 OAT1 326 OAT3 339 OATP1B1 406 OATP1B3 350 OCT1 327 OCT2 355 P-gp 1537	CYP1A2 701 CYP2B6 547

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 95.0	no
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 95.0	no
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 95.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 94.0	no
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf#page=95 Page: 95.0	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 94.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 94.0	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 94.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 94.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 94.0	no
MATE1 308	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 95.0	no
MATE2 263	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 95.0	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 95.0	no
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 95.0	no
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 95.0	no
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 95.0	no
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 95.0	no
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 95.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 95.0	no
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf#page=95 Page: 95.0	yes
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 94.0	yes	yes (co-administration study) Comment: larotrectinib increased midazolam both AUC and Cmax by 1.7-fold Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 94.0

Drug as victim

Target	Modality	Activity	Clinical evidence
OAT1 326	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 93, 94	no
OAT3 339	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 93, 94	no
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 93, 94	no
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 93, 94	no
OCT1 327	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 93, 94	no
OCT2 355	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 93, 94	no
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 93, 94	yes [Km >300 uM]
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 93, 94, 106	yes [Km >300 uM]	yes (co-administration study) Comment: rifampin increased larotrectinib AUC by 1.7-fold and Cmax by 1.8-fold Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 93, 94, 106
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf#page=95 Page: 95, 104, 105	yes	yes (co-administration study) Comment: coadministration with midazolam increased midazolam AUC and Cmax by 1.7-fold; itraconazole increased larotrectinib AUC by 4.3-fold and Cmax by 2.8-fold; rifampin decreased larotrectinib AUC by 81% and Cmax by 71% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf#page=95 Page: 95, 104, 105

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210861Orig1s000_211710Orig1s000MultidisciplineR.pdf Page: 44, 51, 182

Sourcing

Vendor/Aggregator	ID	URL
AA Blocks	AA00171P	https://www.aablocks.com/goods/Goods/detail?id=AA00171P
Aaron Chemicals	AR0017TH	http://www.aaronchem.com/1223403-58-4
AbMole Bioscience	M6151	http://www.abmole.com/products/loxo-101.html
Acorn PharmaTech	ACN-043424	http://www.acornpharmatech.com/
BioChemPartner	BCP16262	http://www.biochempartner.com/1223403-58-4-BCP16262
Chem Scene	CS-5722	http://www.chemscene.com/1223403-58-4.html
Chemspace	CSSB00025704742	https://chem-space.com/CSSB00025704742
DC Chemicals	DC22338	http://www.dcchemicals.com/product_show-DC22338.html
Excenen	EX-A1981	https://www.excenen.com/searchresultlist.php?id=1223403-58-4
Huateng Pharma	F99712	http://en.huatengsci.com/product/Larotrectinib.html
Lab Network	LN01343982	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01343982
MedChem Express	HY-12866	https://www.medchemexpress.com/LOXO-101.html
Selleck Chemicals	S5860	http://www.selleckchem.com/products/larotrectinib.html
Smolecule	S002173	http://www.smolecule.com/products/s002173
Smolecule	S532504	http://www.smolecule.com/products/s532504
THE BioTek	bt-253135	https://www.thebiotek.com/product/inhibitors/bt-253135
THE BioTek	bt-272566	https://www.thebiotek.com/product/inhibitors/bt-272566
abcr GmbH	AB463081	http://www.abcr.com/shop/en/AB463081
eNovation Chemicals	D572361	https://www.enovationchem.com/ProductDetails.asp?ProductID=D572361

PubMed

Title	Date	PubMed
Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer.	2013 Nov	24162815
An Oncogenic NTRK Fusion in a Patient with Soft-Tissue Sarcoma with Response to the Tropomyosin-Related Kinase Inhibitor LOXO-101.	2015 Oct	26216294
Targeting NTRK fusion in non-small cell lung cancer: rationale and clinical evidence.	2017 Jun	28444624
Rapid Response to Larotrectinib (LOXO-101) in an Adult Chemotherapy-Naive Patients With Advanced Triple-Negative Secretory Breast Cancer Expressing ETV6-NTRK3 Fusion.	2018 Jun	29233640

Sample Use Guides

In Vivo Use Guide

Oral capsule of LOXO-101 (ARRY-470 (FREE BASE)) - 100mg BID

Route of Administration: Oral

In Vitro Use Guide

ARRY-470 is a selective kinase inhibitor with nanomolar activity against TRKA/B/C but no other significant kinase inhibition below 1000nM. Treatment of cells expressing MPRIP- or CD74-NTRK1 with ARRY-470, CEP-701 and, to a lesser extent, crizotinib, inhibited autophosphorylation of RIP-TRKA and CD74-TRKA. It induces cell-cycle arrest in G1 and apoptosis of KM12 cells.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 09:23:09 GMT 2023` Edited by `admin` on `Sat Dec 16 09:23:09 GMT 2023`
Record UNII	RDF76R62ID
Record Status	`Validated (UNII)`
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Name

Type

Language

LAROTRECTINIB SULFATE

Official Name

English

VITRAKVI

Brand Name

English

LAROTRECTINIB SULFATE [USAN]

Common Name

English

1-PYRROLIDINECARBOXAMIDE, N-(5-((2R)-2-(2,5-DIFLUOROPHENYL)-1-PYRROLIDINYL)PYRAZOLO(1,5-A)PYRIMIDIN-3-YL)-3-HYDROXY-, (3S)-, SULFATE (1:1)

Systematic Name

English

Larotrectinib sulfate [WHO-DD]

Common Name

English

ARRY-470 SULFATE

Code

English

LAROTRECTINIB SULFATE [MI]

Common Name

English

(3S)-N-{5-[(2R)-2-(2,5-Difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl}-3-hydroxypyrrolidine-1-carboxamide sulfate (1:1)

Systematic Name

English

LOXO-101 SULFATE

Code

English

LAROTRECTINIB SULFATE [ORANGE BOOK]

Common Name

English

LAROTRECTINIB SULFATE [JAN]

Common Name

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/15/1606