JNJ-38877605

SKU: orb1223562

Description

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.

Key Properties

• CAS Number: 943540-75-8
• MW: 377.3502
• Purity: >98% (HPLC)
• Formula: C₁₉H₁₃F₂N₇
• SMILES: CN1N=C(C2=NN3C(C=C2)=NN=C3C(C4=CC=C5N=CC=CC5=C4)(F)F)C=C1
• Target: c-Met/HGFR
• Solubility: DMSO: ≥ 30 mg/mL

Bioactivity

• In Vivo:
  Animal model: U251 human glioma cells and MDA-MB-231 human breast cancer cells transplanted tumor xenografts. Dosage: 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.
  Read more...
• In Vitro:
  Western blot analysis. Cell line: A549 cells. Concentration: 0.5 μΜ Incubation time: 24 h. Result: 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.
  Read more...

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

JNJ38877605 | JNJ 38877605

Quick Database Links

Gene Symbol

c-Met/HGFR