MK-8033

SKU: orb1296122

Description

MK-8033

Research Area

Signal Transduction

Key Properties

• CAS Number: 1001917-37-8
• MW: 471.53
• Purity: 97.16%
• Formula: C₂₅H₂₁N₅O₃S
• SMILES: Cn1cc(cn1)-c1cnc2ccc3ccc(CS(=O)(=O)NCc4ccccn4)cc3c(=O)c2c1
• Target: c-Met/HGFR
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:1 mg/mL (2.12 mM);DMSO:45 mg/mL (95.43 mM)

Bioactivity

• Target IC50:
  Ron:7 nM|c-Met (WT):1 nM (cell free)|c-Met (N1100Y):1 nM (cell free)
• In Vivo:
  MK-8033 was orally dosed in GTL-16 tumor xenograft bearing mice. Mice were euthanized 1 h after dosing and tested for p-Met (Y1349) in tumors and MK-8033 concentrations in plasma. At 100 mg/kg, essentially complete inhibition of p-Met (Y1349) was achieved. An in vivo IC50 of 1.3 uM was deduced from the relationship between plasma MK-8033 level and Met pY1349. Dosing at 3, 10, 30, and 100 mg/kg resulted in 22, 18, 57, and 86% tumor growth inhibition, respectively, relative to the tumor from vehicle-treated mice .
• In Vitro:
  MK-8033 binds 3-fold more tightly to phosphorylated c-Met kinase domain (Kd: 3.2 nM) than to its unphosphorylated counterpart (Kd = 10.4 nM). Significantly, MK-8033 potently inhibits the kinase activity of three oncogenic c-Met activation loop mutants, Y1230C, Y1230H, and Y1235D (IC50s: 0.6~1 nM at 50 uM ATP) in addition to other c-Met activating mutants N1100Y and M1250T. MK-8033 potently inhibited GTL-16 proliferation (IC50: 582 nM). By contrast, the HCT116 cell line, which does not harbor basal c-Met activation, was not inhibited by MK-8033 (IC50 > 10000 nM) . MK-8033 radiosensitizer the high-c-Met-expressing EBC-1 and H1993 cells but not the low-c-Met-expressing cell lines A549 and H460. However, irradiation of A549 and H460 cells increased the expression of c-Met protein at 30 minutes after the irradiation. Subsequent targeting of this up-regulated c-Met by using MK-8033 followed by a second radiation dose reduced the clonogenic survival of both A549 and H460 cells. MK-8033reduced the levels of radiation-induced phosphorylated (activated) c-Met in A549 cells .

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

EBC-1, c-Met, cMet, c-Met/HGFR, cMet/HGFR, breast cancer, bladder cancer, anti-tumor, Anti-ancer, inhibit, MK 8033, MK8033, MK-8033, NSCLCs, GTL-16, H1993, Inhibitor, HGFR, radiosensitivity, RON

Compound Identifiers

PubChem CID

45142457