BS-181 hydrochloride is a selective cyclin-dependent kinase inhibitor with an IC50 of 21 nM for the inhibition of CDK-activating kinase. Testing of other CDKs as well as another 69 kinases showed that BS-181 hydrochloride only inhibited CDK2 at concentrations lower than 1 μM, with CDK2 being inhibited 35-fold less potently (IC50 880 nM) than CDK7. In MCF-7 cells, BS-181 hydrochloride inhibited the phosphorylation of CDK7 substrates, promoted cell cycle arrest and apoptosis to inhibit the growth of cancer cell lines.
In vivo, BS-181 (5 mg/kg, 10 mg/kg, i.p.) inhibits the growth of MCF-7 tumors in nude mice. Intravenous (i.v) and i.p administration of 10 mg/kg BS-181 shows rapid clearance. BS-181 (10 mg/kg/d or 20 mg/kg/d, i.p.) significantly inhibits the growth of tumor in a dose-dependent manner compared to the control group.
Cell Experiment | |
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Cell lines | MCF-7 cells |
Preparation method | Exposing MCF-7 cells to BS-181 for 24 hours. For the determination of cell cycle and apoptosis, staining cells with propidium iodide or labeled with Annexin V-FITC, then acquiring labeled cells within 1 hour, by using the RXP cytomics software on a Beckman Coulter Elite ESP, and using Flow Jo v7.2.5 to analyze the data . For the assessment of CDKs, lysing and analyzing cells by western blotting. |
Concentrations | Dissolved in DMSO, final concentration ~50 μM |
Incubation time | 24 hours |
Animal Experiment | |
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Animal models | MCF-7 cells are established in female nu/nu-BALB/c athymic nude mice |
Formulation | Prepared in the vehicle of 10% DMSO / 50 mM HCl / 5% Tween 20 / 85% saline. |
Dosages | 10 or 20 mg/kg |
Administration | Twice daily by i.p. injection |
Molecular Weight | 416.99 |
Formula | C22H32N6.HCl |
CAS Number | 1397219-81-6 |
Solubility (25°C) | Water 85 mg/mL DMSO 45 mg/mL |
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.
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