MK-8033

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

MK-8033 是一种有效、特异性、双重 c-Met/Ron 激酶抑制剂，IC50 为 1/7 nM。

MK-8033 is a potent, specific, dual c-Met/Ron kinases inhibitor with IC50 of 1/7 nM, also potently inhibits oncogenic c-Met activation loop mutants Y1230C, Y1230H and Y1235D with IC50 of 0.6-1.2 nM; MK-8033 is >100-fold selective relative to Ron and c-Met inhibition against a panel of 221 kinases; potently and selectively inhibits growth in c-Met amplified cell lines (GTL-16 proliferation IC50 =582 nM), causes full inhibition of tumor growth in c-Met amplified (GTL-16) subcutaneous tumor xenograft model; synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth.Solid Tumors Phase 1 Clinical

MK-8033 (Compound 11r, 10 μM) displayed 31% inhibition of CYP3A4 (cytochrome P450 3A4).MK-8033 (1 μM, 2 h) inhibits phosphorylation of Y1349 of c-Met (IC50: 0.03 μM) in the c-Met dependent gastric cancer cell line GTL-16.MK-8033 (1-10 μM, 72 h) inhibits GTL-16 cell proliferation (IC50: 0.58 μM).MK-8033 binds more tightly to phosphorylated c-Met (Kd: 3.2 nM) than to its unphosphorylated counterpart (Kd: 10.4 nM), and inhibits oncogenic c-Met activation loop mutants with IC50s ranging from 0.6 to 1 nM. MK-8033 (0.1-10 μM, 2 h) reduces the phosphorylation of c-Met, ERK, and Akt in EBC-1 and H1993 cells.MK-8033 (1 μM, 1 h) sensitizes EBC-1 and H1993 cells (high c-Met-expressing) to radiation.MK-8033 (10 μM, 6 h) enhances γ-H2Ax levels in A549 cells compared to double irradiation and decreases in DNA repair. MK-8033 (2 μM, 72 h) results in reduced cell proliferation, but modest induction of apoptosis in G-alpha protein mutant UM (uveal melanoma) cells.

MK-8033 (Compound 11r, oral administration, 3-100 mg/kg, twice daily for 21 days) inhibits tumor growth in GTL-16 c-Met amplified gastric tumor xenografts.MK-8033 exhibits moderate clearance (t1/2: 0.8 h for rats, 3.1 h for dog) and favorable bioavailability (35% for rats, 33% for dog). Animal Model:Human GTL-16 c-Met amplified gastric tumor xenografts Dosage:3, 10, 30, and 100 mg/kg Administration:Oral administration, twice daily for 21 days Result:Resulted in 22, 18, 57, and 86% tumor growth inhibition at 3, 10, 30, and 100 mg/kg, respectively.

MK 8033 | MK8033

Angiogenesis

c-Met/HGFR

c-Met/HGFR

Cancer

Solid Tumors

1001917-37-8

471.53

C25H21N5O3S

>98% (HPLC)

DMSO: ≥ 46 mg/mL

O=S(CC1=CC=C2C(C(C3=CC(C4=CN(C)N=C4)=CN=C3C=C2)=O)=C1)(NCC5=NC=CC=C5)=O

5H-Benzo[4,5]cyclohepta[1,2-b]pyridine-7-methanesulfonamide, 3-(1-methyl-1H-pyrazol-4-yl)-5-oxo-N-(2-pyridinylmethyl)-

(-20℃)

With Ice Pack

≥ 2 years