ZOLIGRATINIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C20H16N6O
Molecular Weight	356.3806
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=NC2=C(N1)C=C(C=C2)N3N=CC(C(=O)C4=CC5=C(N4)C=CC=C5)=C3N

InChI

InChIKey=BEMNJULZEQTDJY-UHFFFAOYSA-N

InChI=1S/C20H16N6O/c1-11-23-16-7-6-13(9-17(16)24-11)26-20(21)14(10-22-26)19(27)18-8-12-4-2-3-5-15(12)25-18/h2-10,25H,21H2,1H3,(H,23,24)

HIDE SMILES / InChI

Molecular Formula	C20H16N6O
Molecular Weight	356.3806
Charge	0
Count

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26438159
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/25169980

CH5183284/Debio 1347 is selective and orally available fibroblast growth factor receptors: FGFR1, FGFR2, and FGFR3 inhibitor that has a unique chemical scaffold. By interacting with unique residues in the ATP-binding site of FGFR1, FGFR2, or FGFR3, CH5183284/Debio 1347 selectively inhibits there receptors, but does not inhibit kinase insert domain receptor (KDR) or other kinases. CH5183284/Debio 1347 will provide therapeutic opportunities for patients who have FGFR genetic alterations and patients with acquired resistance to existing FGFR selective inhibitors that contain the common methoxy moieties.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Fibroblast growth factor receptor 1 45 Target ID: CHEMBL3650 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25169980	Inhibitor 8297	9.3 nM [IC50]
Fibroblast growth factor receptor 2 25 Target ID: CHEMBL4142 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25169980	Inhibitor 8297	7.6 nM [IC50]
Fibroblast growth factor receptor 3 32 Target ID: CHEMBL2742 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25169980	Inhibitor 8297	22.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Solid tumors 145 Sources: https://clinicaltrials.gov/ct2/show/NCT01948297	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
1125 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30745300/	60 mg 1 times / day steady-state, oral dose: 60 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DEBIO-1347 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
425 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30745300/	30 mg 1 times / day steady-state, oral dose: 30 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DEBIO-1347 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2486 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30745300/	80 mg 1 times / day steady-state, oral dose: 80 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DEBIO-1347 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2729 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30745300/	150 mg 1 times / day steady-state, oral dose: 150 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DEBIO-1347 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
469 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30745300/	40 mg 1 times / day steady-state, oral dose: 40 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DEBIO-1347 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
881 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30745300/	40 mg 1 times / day steady-state, oral dose: 40 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DEBIO-1347 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
114 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30745300/	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DEBIO-1347 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1373 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30745300/	110 mg 1 times / day steady-state, oral dose: 110 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DEBIO-1347 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
291 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30745300/	20 mg 1 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DEBIO-1347 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
14744 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30745300/	60 mg 1 times / day steady-state, oral dose: 60 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DEBIO-1347 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3551 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30745300/	30 mg 1 times / day steady-state, oral dose: 30 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DEBIO-1347 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
41994 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30745300/	80 mg 1 times / day steady-state, oral dose: 80 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DEBIO-1347 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
44185 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30745300/	150 mg 1 times / day steady-state, oral dose: 150 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DEBIO-1347 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4700 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30745300/	40 mg 1 times / day steady-state, oral dose: 40 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DEBIO-1347 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
9567 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30745300/	40 mg 1 times / day steady-state, oral dose: 40 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DEBIO-1347 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
973 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30745300/	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DEBIO-1347 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3910 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30745300/	20 mg 1 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	DEBIO-1347 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P009D2X	https://www.1pchem.com/search?query=1P009D2X
AChemBlock	Q65616	http://www.achemblock.com/catalogsearch/result/?q=Q65616
ApexBio Technology	B4985	https://www.apexbt.com/catalogsearch/result/?q=B4985
AstaTech	44163	http://astatechinc.com/CPSResult.php?CRNO=44163
BLD Pharm	BD566145	http://www.bldpharm.com/search/Search.html?keyword=BD566145
Cayman Chemical	17120	http://www.caymanchem.com/app/template/Product.vm/catalog/17120
Chem Scene	CS-5504	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-5504
ChemShuttle	140484	https://www.chemshuttle.com/catalogsearch/result/?q=140484
Excenen	EX-A1122	http://www.excenen.com/searchresultlist.php?id=EX-A1122
Lab Network	LN01314022	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01314022
MedChem Express	HY-19957	https://www.medchemexpress.com/search.html?q=HY-19957&ft=&fa=&fp=
MolPort	MolPort-035-944-333	https://www.molport.com/shop/molecule-link/MolPort-035-944-333
MuseChem	I001069	https://www.musechem.com/product/I001069.html
Selleck Chemicals	S7665	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7665
ShangHai Biochempartner	BCP14354	http://www.biochempartner.com/search_BCP14354
Toronto Research Chemicals	C291695	https://www.trc-canada.com/product-detail/?CatNum=C291695
eMolecules	50428956	https://orderbb.emolecules.com/search/#?query=50428956
mcule	MCULE-5718068131	https://mcule.com/MCULE-5718068131/

PubMed

Title	Date	PubMed
The fibroblast growth factor receptor genetic status as a potential predictor of the sensitivity to CH5183284/Debio 1347, a novel selective FGFR inhibitor.	2014 Nov	25169980
ERK Signal Suppression and Sensitivity to CH5183284/Debio 1347, a Selective FGFR Inhibitor.	2015 Dec	26438159

Patents

Sample Use Guides

In Vivo Use Guide

Adaptive doses of Debio1347 (CH5183284): (10 mg to 210 mg/day) until the recommended dose is determined.

Route of Administration: Oral

In Vitro Use Guide

MAPK pathway suppression by CH5183284/Debio 1347 in FGFR-altered cancer cell lines was investigated. Cells were treated with 1 μmol/L CH5183284/Debio 1347. It was confirmed that the ERK (GSE15417) and MEK signatures were suppressed by CH5183284/Debio 1347 only in sensitive cell lines harboring FGFR alterations. Consistent with this, suppression of phospho-ERK by a 2-hour treatment with CH5183284/Debio 1347 was observed in seven cancer cell lines harboring FGFR alterations.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 01:54:43 UTC 2023` Edited by `admin` on `Sat Dec 16 01:54:43 UTC 2023`
Record UNII	NR9ZYH80Z8
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ZOLIGRATINIB

Official Name

English

Zoligratinib [WHO-DD]

Common Name

English

(5-AMINO-1-(2-METHYL-1H-BENZIMIDAZOL-6-YL)-1H-PYRAZOL-4-YL)-1H-INDOL-2-YLMETHANONE

Common Name

English

DEBIO-1347

Common Name

English

zoligratinib [INN]

Common Name

English

(5-AMINO-1-(2-METHYL-3H-BENZIMIDAZOL-5-YL)PYRAZOL-4-YL)-(1H-INDOL-2-YL)METHANONE

Common Name

English

METHANONE, (5-AMINO-1-(2-METHYL-1H-BENZIMIDAZOL-6-YL)-1H-PYRAZOL-4-YL)-1H-INDOL-2-YL-

Systematic Name

English

CH-5183284

Code

English

CH5183284

Code

English

Code System Code Type Description

PUBCHEM

66555680