MSC2530818

SKU: orb1296089

Description

MSC2530818

Research Area

Cell Biology

Key Properties

• CAS Number: 1883423-59-3
• MW: 340.81
• Purity: 99.33%
• Formula: C₁₈H₁₇ClN₄O
• SMILES: Cc1n[nH]c2ncc(cc12)C(=O)N1CCC[C@H]1c1ccc(Cl)cc1
• Target: CDK
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:4 mg/mL (11.74 mM);DMSO:120 mg/mL (352.1 mM)

Bioactivity

• Target IC50:
  CDK8:2.6 nM (cell free)
• In Vivo:
  Treatment with MSC2530818 in mice carrying tumors resulted in a notable reduction of tumor growth, presenting T/C ratios of 49% and 57%. This compound was well accepted, showing no impact o the body weight of mice under a daily (qd) administration regimen, aside from controllable body weight loss. Additionally, its pharmacokinetic profile in humans indicates a low clearance (0.14 L/h/kg) and a s All volume of distribution at steady-state (0.48 L/kg), leading to a brief estimated terminal half-life of 2.4 hours. Moreover, physiologically based pharmacokinetic simulations predict that MSC2530818 could achieve an oral bioavailability of at least 75% when administered up to a daily dose of 500 mg.
• In Vitro:
  MSC2530818 binds to CDK8 and CDK19 with a similar affinity (4 nM) and shows potent Inhibition of phospho-STAT1SER727, a biomarker of CDK8 activity, in SW620 human colorectal carcinoma cells (pSTAT1SER727 IC50 ± nM). It also inhibits WNT-dependent transcription in human cancer cell lines with activated WNT signaling, including LS174T (β-catenin mutant, IC50 3 ± nM), COLO205 (APC mutant, IC50 ± nM), and WNT3a li and-dependent Reporter readout in PA-1 cells IC50 5 ± 0 nM). Moreover, MSC2530818 exhibits a low efflux ratio in Caco-2 cells and does not inhibit any cytochrome P450 subtypes.
• Animal Research:
  MSC2530818 is assessed in an established SW620 human colorectal cancer xenograft model in f Male NCr athymic mice. Tumor-bearing mice are treated orally with MSC2530818 (50 mg/kg bid or 100 mg/kg qd) for 16 dayss. Tumor weights are measured and body weights are monitored.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Disclaimer: For research use only

Alternative Names

inhibit, MSC 2530818, MSC2530818, MSC-2530818, Inhibitor, Cyclin dependent kinase, CDK, CDK8

Compound Identifiers

PubChem CID

118879529