JNJ-38877605

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

JNJ-38877605 是一种有效的、选择性的、ATP 竞争性的 c-Met 催化活性抑制剂，IC50 为 4 nM。

JNJ-38877605 is a potent, selective, ATP-competitive inhibitor of catalytic activity c-Met with IC50 of 4 nM; exhibits >600-fold selectivity (cFMS IC50=2.6 uM; the next potently inhibited kinase) against a panel of 250 diverse tyrosine and serine-threonine kinases; inhibits Met phosphorylation associated with dose-dependent tumor growth inhibition in tumor xenograft models; orally bioavailable.Solid Tumors Phase 1 Discontinued.

Western Blot Analysis Cell Line:A549 cells Concentration:0.5 μΜIncubation Time:24 hResult:Inhibited CPNE1 (HY-P70097)-induced MET phosphorylation and activation of the MET signaling pathway.Western Blot Analysis Cell Line:3T3-L1 cells Concentration:5,10,20 μΜ Incubation Time:2, 5, 8 day Result:Strongly inhibited c-Met phosphorylation without altering its total expression resulted in less lipid accumulation and triglyceride (TG) content with no cytotoxicity. Reduced the expression of adipogenic regulators, including CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), acetyl CoA carboxylase (ACC), and perilipin A. Increased cAMP-activated protein kinase (AMPK) and liver kinase B-1 (LKB-1) phosphorylation but decreased ATP levels.

Animal Model:U251 human glioma cells and MDA-MB-231 human breast cancer cells transplanted tumor xenograftsDosage:50 mg/kg Administration:Oral gavage (p.o.) once daily for 13 days Result:Counteracted radiation-induced invasiveness, promoted apoptosis.Animal Model:Met-addicted GTL16 xenografts mice model Dosage:40 mg/kg Administration:Oral gavage (p.o.) once daily for 3 days Result:Decreased in the plasma levels of human IL-8 (from 0.150 to 0.050 ng/ml) and GROa (from 0.080 to 0.030 ng/ml).Diminished The blood concentration of uPAR also by more than 50% .Inhibited Met-addicted xenografts induced consistent changes in plasma concentration of IL8, GROa, uPAR and IL-6.

JNJ38877605 | JNJ 38877605

Angiogenesis

c-Met/HGFR

c-Met

Cancer

Solid Tumors

943540-75-8

377.3502

C19H13F2N7

>98% (HPLC)

DMSO: ≥ 30 mg/mL

CN1N=C(C2=NN3C(C=C2)=NN=C3C(C4=CC=C5N=CC=CC5=C4)(F)F)C=C1

Quinoline, 6-[difluoro[6-(1-methyl-1H-pyrazol-4-yl)-1,2,4-triazolo[4,3-b]pyridazin-3-yl]methyl]-

(-20℃)

With Ice Pack

≥ 2 years