JNJ-10198409

CAS

627518-40-5

Catalog Number

ACM627518405-1

Category

Inhibitors

Molecular Weight

325.34

Molecular Formula

C18H16FN3O2

MSDS COA Spec Sheet

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Specification

Description

JNJ-10198409, also known as RWJ-540973, is an inhibitor of PDGF-BB tyrosine kinase with an IC50 value of 4.2 nM. JNJ-10198409 is a competitive antagonist of the ATP binding and hydrolysis at this receptor, resulting in a dose dependent inhibition of tumor growth and angiogenesis.

Synonyms

JNJ-10198409; JNJ 10198409; JNJ10198409; RWJ-540973; RWJ 540973; RWJ540973

IUPAC Name

N-(3-fluorophenyl)-1,4-dihydro-6,7-dimethoxy-indeno[1,2-c]pyrazol-3-amine

Canonical SMILES

COC1=CC2=C(C=C1OC)CC3=C2NN=C3NC4=CC=CC(F)=C4

InChI

InChI=1S/C18H16FN3O2/c1-23-15-7-10-6-14-17(13(10)9-16(15)24-2)21-22-18(14)20-12-5-3-4-11(19)8-12/h3-5,7-9H,6H2,1-2H3,(H2,20,21,22)

InChI Key

ZDNURMVOKAERHZ-UHFFFAOYSA-N

Solubility

Soluble in DMSO

Appearance

Solid powder

Shelf Life

>2 years if stored properly

Storage

Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).

Biological Target

JNJ-10198409 is a relatively selective, orally active, and ATP competitive PDGF-RTK (platelet-derived growth factor receptor tyrosine kinase) inhibitor (IC50=2 nM). JNJ-10198409 has good activity against PDGFR-β kinase (IC50=4.2 nM) and PDGFR-α kinase (IC50=45 nM).

Drug Formulation

This drug may be formulated in DMSO

Elemental Analysis

C, 66.45; H, 4.96; F, 5.84; N, 12.92; O, 9.84

Exact Mass

325.1227

HS Tariff Code

2934.99.9001

In Vitro Activity

JNJ-10198402 (J101) was confirmed as blocking cell proliferation in GNS cells, as no increases in total cell number were recorded. Surprisingly however, J101 was found to induce a ~7-fold increase in the numbers of mitotic objects scored during a two-day period compared to DMSO controls (Figure 2B). The increase in cells undergoing mitosis without a concomitant increase in total cell numbers (Figure 2C) suggested that mitotic arrest might be triggered in GNS cultures, but not NS cells, following J101 exposure.
Reference: PLoS One. 2013 Oct 30;8(10):e77053. https://pubmed.ncbi.nlm.nih.gov/24204733/

In Vivo Activity

Hence, this study investigated the in vivo pharmacodynamic activity of JNJ-10198409, a relatively selective inhibitor of platelet-derived growth factor receptor tyrosine kinase (PDGF-RTK), in tumor tissues after administering the compound orally in a nude mouse xenograft model of human LoVo colon cancer. Computer-assisted image analysis was then used to directly compare the ratio of ph-PLCgamma1 to pan-PLCgamma1 immunolabeling intensities in serial sections (5 mum) of tumors obtained from vehicle- and JNJ-10198409-treated tumor-bearing mice. This data showed statistically significant, dose-dependent differences in the ph-PLC/pan-PLC ratio among the four treatment groups (vehicle, 25, 50, and 100 mg/kg b.i.d.). These results confirmed this compound's ability to suppress PDGF-RTK downstream signaling in tumor tissues in vivo.
Reference: Mol Cancer Ther. 2005 Aug;4(8):1198-204. https://pubmed.ncbi.nlm.nih.gov/16093435/

Shipping

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Stock Solution Storage

0-4 °C for short term (days to weeks), or -20 °C for long term (months).