BS-181 HCl |
| Catalog No.GC13690 |
BS-181 HCl es un inhibidor de CDK7 altamente selectivo con IC50 de 21 nM y > 40 veces mÁs selectivo para CDK7 que para CDK1, 2, 4, 5, 6 o 9.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1397219-81-6
Sample solution is provided at 25 µL, 10mM.
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IC50: 21 nm (CDK7)
Normal progression through the cell cycle requires the sequential action of cyclin-dependent kinases CDK1, CDK2, CDK4, and CDK6. Direct or indirect deregulation of CDK activity is a feature of almost all cancers and has led to the development of CDK inhibitors as anticancer agents.BS-181 is a highly selective CDK7 inhibitor with IC50 of 21 nM. ; >40-fold selective for CDK7 than CDK1, 2, 4, 5, 6, or 9.
In vitro: BS-181, inhibited CAK activity with an IC50 of 21 nmol/L. Testing of other CDKs as well as another 69 kinases showed that BS-181 only inhibited CDK2 at concentrations lower than 1 μmol/L, with CDK2 being inhibited 35-fold less potently (IC50 880 nmol/L) than CDK7. In MCF-7 cells, BS-181 inhibited the phosphorylation of CDK7 substrates, promoted cell cycle arrest and apoptosis to inhibit the growth of cancer cell lines [1].
In vivo: BS-181 was stable in vivo with a plasma elimination half-life in mice of 405 minutes after i.p. administration of 10 mg/kg. The same dose of drug inhibited the growth of MCF-7 human xenografts in nude mice. BS-181 therefore provides the first example of a potent and selective CDK7 inhibitor with potential as an anticancer agent [1].
Clinical trial: BS-181 is currently in the preclinical development and non clinical trial is ongoing.
Reference:
[1] Ali S, Heathcote DA, Kroll SH, Jogalekar AS, Scheiper B, Patel H, Brackow J, Siwicka A, Fuchter MJ, Periyasamy M, Tolhurst RS, Kanneganti SK, Snyder JP, Liotta DC, Aboagye EO, Barrett AG, Coombes RC. The development of a selective cyclin-dependent kinase inhibitor that shows antitumor activity. Cancer Res. 2009;69(15):6208-15.
| Kinase experiment [1]: | |
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In vitro kinase inhibition. |
Inhibition of CDK7 activity was measured by incubation of increasing amounts of BS-181 HCl with purified recombinant CDK7/CycH/MAT1 complex, followed by measurement of free ATP remaining in the reaction using a luciferase assay, luciferase activity therefore providing a measure of inhibition of CDK7 activity for the determination of IC50. |
| Cell experiment [1]: | |
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Cell lines |
MCF-7 cells |
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Preparation method |
The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20 °C for several months. |
|
Reaction Conditions |
50 μM; 24 hrs |
|
Applications |
In MCF-7 cells, BS-181 HCl inhibited the phosphorylation of CDK7 substrates, and promoted cell cycle arrest and apoptosis to inhibit the growth of cancer cell lines. |
| Animal experiment [1]: | |
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Animal models |
Mice bearing MCF-7 xenografts |
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Dosage form |
10 or 20 mg/kg; i.p.; b.i.d., for 2 weeks |
|
Applications |
In mice bearing MCF-7 xenografts, BS-181 HCl inhibited tumor growth in a dose-dependent manner, without apparent toxicity. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Ali S, Heathcote DA, Kroll SH, Jogalekar AS, Scheiper B, Patel H, Brackow J, Siwicka A, Fuchter MJ, Periyasamy M, Tolhurst RS, Kanneganti SK, Snyder JP, Liotta DC, Aboagye EO, Barrett AG, Coombes RC. The development of a selective cyclin-dependent kinase inhibitor that shows antitumor activity. Cancer Res. 2009;69(15):6208-15. | |
| Cas No. | 1397219-81-6 | SDF | |
| Chemical Name | 5-N-(6-aminohexyl)-7-N-benzyl-3-propan-2-ylpyrazolo[1,5-a]pyrimidine-5,7-diamine;hydrochloride | ||
| Canonical SMILES | CC(C)C1=C2N=C(C=C(N2N=C1)NCC3=CC=CC=C3)NCCCCCCN.Cl | ||
| Formula | C22H32N6.HCl | M.Wt | 416.99 |
| Solubility | ≥ 20.85mg/mL in DMSO, ≥ 6.49 mg/mL in EtOH with ultrasonic | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3981 mL | 11.9907 mL | 23.9814 mL |
| 5 mM | 0.4796 mL | 2.3981 mL | 4.7963 mL |
| 10 mM | 0.2398 mL | 1.1991 mL | 2.3981 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 8 reference(s) in Google Scholar.)
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