SGX-523

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

SGX-523 是一种有效的、选择性 ATP 竞争性 MET 受体酪氨酸激酶抑制剂，IC50 为 4 nM。

SGX-523 is a potent, selective ATP-competitive inhibitor of MET receptor tyrosine kinase with IC50 of 4 nM, does not inhibit RON and a panel of kinases; shows higher affinity for unphosphorylated form of MET (Ki = 2.7 nM) versus the more active phospho-MET (Ki=23 nM); inhibits MET-mediated signaling, cell proliferation, and cell migration at nanomolar concentrations but has no effect on signaling dependent on other protein kinases; inhibits MET autophosphorylation with IC50 of 40 nM in GTL16 cells, inhibits MET-dependent tumor growth in vivo.Solid Tumors Phase 1 Discontinued(In Vitro):SGX523 shows ATP-competitive inhibition with higher apparent affinity for the less active, unphosphorylated form of MET [MET-KD(0P), Ki=2.7 nM] versus the more active phospho-enzyme [MET-KD(3P), Ki=23 nM].SGX523 inhibits the growth of gastric and lung cancer cell lines with amplification of the MET gene but has no effect, even at high micromolar concentration, on cell lines with normal MET gene copy number. TheIC50s of 0.02, 0.113, and 0.035 μM for NSCLC H1993, gastric cncer MKN45, and gastric cancer Hs746T cells, respectively.The IC50 value for the inhibition of MET autophosphorylation is 0.040 μM in GTL16 cells.SGX523 (0.5, 1.5, 4.6, 13.7, 41, 123, 370, 1100, 3300, 10000 nM; 1 hour) inhibits MET autophosphorylation without affecting total MET or extracellular signal-regulated kinase protein levels in HGF-stimulated A549 cells.(In Vivo):SGX523 exhibits antitumor activity in vivo. SGX523 inhibits MET-dependent tumor growth.

SGX523 shows ATP-competitive inhibition with higher apparent affinity for the less active, unphosphorylated form of MET [MET-KD(0P), Ki=2.7 nM] versus the more active phospho-enzyme [MET-KD(3P), Ki=23 nM].SGX523 inhibits the growth of gastric and lung cancer cell lines with amplification of the MET gene but has no effect, even at high micromolar concentration, on cell lines with normal MET gene copy number. TheIC50s of 0.02, 0.113, and 0.035 μM for NSCLC H1993, gastric cncer MKN45, and gastric cancer Hs746T cells, respectively.The IC50 value for the inhibition of MET autophosphorylation is 0.040 μM in GTL16 cells. SGX523 (0.5, 1.5, 4.6, 13.7, 41, 123, 370, 1100, 3300, 10000 nM; 1 hour) inhibits MET autophosphorylation without affecting total MET or extracellular signal-regulated kinase protein levels in HGF-stimulated A549 cells. Cell Viability Assay Cell Line:Gastric cancer cell line GTL16 Concentration:4.6, 14, 40, 120, 370, 1100, 3300, 10000 nM Incubation Time:1 hours Result:Abolished constitutive signaling induced by MET gene amplification.

SGX523 exhibits antitumor activity in vivo. SGX523 inhibits MET-dependent tumor growth. Animal Model:Female Harlan nude mice (athymic nu/nu) were s.c. implanted with U87 cells Dosage:10 or 30 mg/kg Administration:Oral gavage; twice daily starting at day 5 for 22 days Result:Potently inhibited U87MG tumor growth at a dose of 10 mg/kg administered twice daily.Led to clear regression of U87MG tumors at 30 mg/kg dosed twice daily.

SGX523 | SGX 523

Angiogenesis

c-Met/HGFR

Abl|B-Raf(V599E)|c-Met|C-Raf|p38α

Cancer

Solid Tumors

1022150-57-7

359.4077

C18H13N7S

>98% (HPLC)

DMSO: ≥ 3.6 mg/mL

CN1N=CC(C2=NN3C(C=C2)=NN=C3SC4=CC=C5N=CC=CC5=C4)=C1

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

(-20℃)

With Ice Pack

≥ 2 years