JNJ-38877605

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H13F2N7
Molecular Weight	377.3502
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C=C(C=N1)C2=NN3C(C=C2)=NN=C3C(F)(F)C4=CC=C5N=CC=CC5=C4

InChI

InChIKey=JRWCBEOAFGHNNU-UHFFFAOYSA-N

InChI=1S/C19H13F2N7/c1-27-11-13(10-23-27)16-6-7-17-24-25-18(28(17)26-16)19(20,21)14-4-5-15-12(9-14)3-2-8-22-15/h2-11H,1H3

HIDE SMILES / InChI

Description
Sources: https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=594157
Curator's Comment: description was created based on several sources, including: DOI:10.1158/1538-7445.AM10-3628 | https://www.ncbi.nlm.nih.gov/pubmed/25745036

JNJ-38877605 is an orally available, small molecule inhibitor of the proto-oncogene c-Met (hepatocyte growth factor receptor [HGFR]) with potential antineoplastic activity. c-Met inhibitor JNJ-38877605 selectively binds to c-Met, thereby inhibiting c-Met phosphorylation and disrupting c-Met signal transduction pathways. JNJ-38877605 was in Phase I clinical trials. Combined clinical and correlative preclinical studies suggest that renal toxicity of JNJ-38877605 is caused by the formation of species-specific insoluble metabolites. These observations preclude further clinical development of JNJ-38877605.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Hepatocyte growth factor receptor 54 Target ID: CHEMBL3717 Sources: DOI:10.1158/1538-7445.AM10-3628	Inhibitor 8297		4.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Cancer 592 Sources: DOI: 10.1158/1538-7445 http://adisinsight.springer.com/trials/700032914	Primary	Phase I 428	Unknown Approved Use Unknown
Non-small cell lung cancer 206 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25806189	Primary	Preclinical	Unknown Approved Use Unknown
Metastatic colorectal cancer 14 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21447729	Primary	Preclinical	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
177 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25745036	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:		JNJ-38877605 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
416 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25745036	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:		JNJ-38877605 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
523 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25745036	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:		JNJ-38877605 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
937 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25745036	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:		JNJ-38877605 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25745036	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:		JNJ-38877605 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 substrate 1737	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461	AO 16

Drug as perpetrator

Target	Modality	Activity
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=440681263	inconclusive [IC50 16.933 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=440681263	inconclusive [IC50 21.3174 uM]
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363677254	inconclusive [IC50 8.1995 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=440681263	yes [IC50 3.0112 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
AO 16	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/30284817/	yes
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25745036/	yes

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY107053	https://www.001chemical.com/chem/search?q=DY107053
1PlusChem LLC	1P01DOA9	https://www.1pchem.com/search?query=1P01DOA9
AK Scientific	SYN1047	https://aksci.com/item_detail.php?cat=SYN1047
AK Scientific	X7476	https://aksci.com/item_detail.php?cat=X7476
AOBIOUS INC	AOB87321	http://aobious.com/aobious/search?search_query=AOB87321
ApexBio Technology	A5092	https://www.apexbt.com/catalogsearch/result/?q=A5092
AstaTech	C77250	http://astatechinc.com/CPSResult.php?CRNO=C77250
BLD Pharm	BD225171	http://www.bldpharm.com/search/Search.html?keyword=BD225171
BOC Sciences	943540-75-8	http://www.bocsci.com/description.asp?cas=943540-75-8
Capot Chemical	22454	https://www.capotchem.com/search.do?q=22454
Chem Scene	CS-0031	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0031
ChemShuttle	112407	https://www.chemshuttle.com/catalogsearch/result/?q=112407
Debye Scientific	DB-000659	https://www.debyesci.com/index.php?id=product&ext[cno]=DB-000659
Excenen	EX-A2081	http://www.excenen.com/searchresultlist.php?id=EX-A2081
Hairui	HR118316	http://www.hairuichem.com/en/product/search.do?q=HR118316
KeyOrganics	AS-16207	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-16207
Lab Network	LN01331014	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01331014
Lab Seeker	SC-48063	http://www.labseeker.com/search.php?keywords=SC-48063&category=0
LabSeeker	SC-48063	http://www.labseeker.com/search.php?keywords=SC-48063&category=0
Matrix Scientific	132610	http://www.matrixscientific.com/132610.html
MedChem Express	HY-50683	https://www.medchemexpress.com/search.html?q=HY-50683&ft=&fa=&fp=
MolPort	MolPort-009-679-418	https://www.molport.com/shop/molecule-link/MolPort-009-679-418
Molcore	MC107053	http://www.molcore.com/CatMC107053.html
ShangHai Biochempartner	BCP01812	http://www.biochempartner.com/search_BCP01812
TargetMol	T6095	https://www.targetmol.com/search?keyword=T6095
Toronto Research Chemicals	J212505	https://www.trc-canada.com/product-detail/?CatNum=J212505
eMolecules	31507610	https://orderbb.emolecules.com/search/#?query=31507610
eNovation Chemicals	D395274	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D395274&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-8471857466	https://mcule.com/MCULE-8471857466/

PubMed

Title	Date	PubMed
MET inhibitors in combination with other therapies in non-small cell lung cancer.	2012 Dec	25806189
Effectiveness of inhibitor rapamycin, saracatinib, linsitinib and JNJ-38877605 against human prostate cancer cells.	2015	26131286
The c-Met Tyrosine Kinase Inhibitor JNJ-38877605 Causes Renal Toxicity through Species-Specific Insoluble Metabolite Formation.	2015 May 15	25745036

Patents

Sample Use Guides

In Vivo Use Guide

60 mg once daily (21-day treatment cycle)

Route of Administration: Oral

In Vitro Use Guide

In EBC1, GTL16, NCI-H1993, and MKN45 cells, JNJ-38877605 (500 nM) leads to a significant reduction of phosphorylation of Met.

Name

Type

Language

JNJ-38877605

Common Name

English

QUINOLINE, 6-(DIFLUORO(6-(1-METHYL-1H-PYRAZOL-4-YL)-1,2,4-TRIAZOLO(4,3-B)PYRIDAZIN-3-YL)METHYL)-

Systematic Name

English

Code System Code Type Description

EPA CompTox

DTXSID20677253