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

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

Molecular Formula	C19H13F2N7
Molecular Weight	377.3502
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

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

Description

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	Inhibitor 8,297		4.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Cancer 592	Primary	Phase I 428	Unknown
Non-small cell lung cancer 206	Primary	Preclinical	Unknown
Metastatic colorectal cancer 14	Primary	Preclinical	Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
177 ng/mL	20 mg 1 times / day multiple, oral		JNJ-38877605 plasma	Homo sapiens
416 ng/mL	60 mg single, oral		JNJ-38877605 plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
523 ng × h/mL	20 mg 1 times / day multiple, oral		JNJ-38877605 plasma	Homo sapiens
937 ng × h/mL	60 mg single, oral		JNJ-38877605 plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.6 h	60 mg single, oral		JNJ-38877605 plasma	Homo sapiens

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1,587 substrate 1,737	inhibitor 1,767	inhibitor 1,852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1,461	AO 16

Drug as perpetrator

Show entries

Target	Modality	Activity
CYP2D6 1,891	inhibitor 3,277	inconclusive [IC50 16.933 uM]
CYP3A4 1,925	inhibitor 3,277	inconclusive [IC50 21.3174 uM]
P-gp 1,650	inhibitor 3,277	inconclusive [IC50 8.1995 uM]
CYP2C9 1,819	inhibitor 3,277	yes [IC50 3.0112 uM]

Showing 1 to 4 of 4 entries

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Drug as victim

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Target	Modality	Activity	Metabolite	Clinical evidence
AO 16	substrate 3,367	yes
CYP3A4 1,737	substrate 3,367	yes

Showing 1 to 2 of 2 entries

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Sourcing

Sourcing

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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

Showing 1 to 5 of 29 entries

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PubMed

Show entries

Title	Date	PubMed
MET inhibitors in combination with other therapies in non-small cell lung cancer.	2012 Dec	25806189
The c-Met Tyrosine Kinase Inhibitor JNJ-38877605 Causes Renal Toxicity through Species-Specific Insoluble Metabolite Formation.	2015 May 15	25745036