In vitro: MSC2530818 binds to CDK8 and CDK19 with similar affinity (4 nM) and shows potent inhibition of phospho-STAT1SER727 in SW620 human colorectal carcinoma cells (IC50=8 ± 2 nM). It also demonstrates potent inhibition of WNT-dependent transcription in human cancer cell lines that have constitutively activated WNT signaling. MSC2530818 is a soluble CDK8 inhibitor with high permeability and low efflux ratio in Caco-2 cells (ER = 1.5) and does not inhibit any cytochrome P450 subtypes (Cyp IC50s > 20 μM).
In vivo: MSC2530818 shows acceptable pharmacokinetics (PK) in all tested preclinical species (mouse, rat, dog). It demonstrates reduction of tumor growth rates of established human SW620 colorectal carcinoma xenografts.
Cell Experiment | |
---|---|
Cell lines | |
Preparation method | |
Concentrations | |
Incubation time |
Animal Experiment | |
---|---|
Animal models | NCr athymic mice |
Formulation | kolliphor 20% w/v in water |
Dosages | 50 mg/kg bid or 100 mg/kg qd |
Administration | p.o. |
Molecular Weight | 340.81 |
Formula | C18H17ClN4O |
CAS Number | 1883423-59-3 |
Solubility (25°C) | 68 mg/mL in DMSO |
Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
Related CDK Products |
---|
PF-07224826
PF-07224826 is a CDK2/4/6 inhibitor. |
INCB123667
INCB123667 is a CDK2 inhibitor. |
Senexin B
Senexin B is a potent, orally active CDK8/19 inhibitor with Kd values of 140 nM and 80 nM for CDK8 and CDK19, respectively. |
Q901
Q901 is a CDK7 inhibitor for tumor-related studies. |
NUV-422
NUV-422 is a CDK2/4/6 inhibitor that can be used in studies related to malignant gliomas. |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.