| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
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| Targets |
CKIα CDK7 1.3 nM (Kd) CDK9 4 nM (Kd)
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|---|---|
| ln Vitro |
Casein Kinase inhibitor A51 (0.05-3.2 μM; 18 hours) treatment of RKO cells eliminated most of the Ser45 phosphorylation signal and the subsequent GSK3 phosphorylation cascade, which led to the stabilization of β-catenin, in a manner similar to CKIα depletion[1]. At 160 nM or less, the casein kinase inhibitor A51 is very effective at causing leukemia cells to undergo apoptosis, mostly due to its ability to stabilize p53[1]. MYC, MDM2, and the anti-apoptotic oncogene MCL1 are all eliminated by the casein kinase inhibitor A51 (0.08-2 μM; 6.5 hours). A51, a casein kinase inhibitor, significantly decreases the mRNA expression of MDM2 and MYC while increasing the expression of Wnt targets AXIN2 and CCND1 (Cyclin D1)[1].
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| ln Vivo |
When the percentage of leukemia cells in the bone marrow is greater than 1.5% of total cells, 8 days after leukemia cell injection, oral medication (Casein Kinase inhibitor A51; 5 mg/kg/day) is started. Every mouse treated with A51 exhibits normal organ morphology, histology, and blood counts[1]. Rapid oral absorption is shown in pharmacokinetic investigations of the Casein Kinase inhibitor A51 at 20 mg/kg, with Tmax values of 0.5-2 hr, Cmax values of 1060 ng/mL, T1/2 values of 2.5 hr, and area under the curve (AUC) values of 3680 (ng*hr/mL)[1].
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: MV4-11 cells Tested Concentrations: 0.08 μM, 0.6 μM, 2 μM Incubation Duration: 6.5 hrs (hours) Experimental Results: Abolishes the expression of MYC, MDM2, and the anti-apoptotic oncogene MCL1. |
| References | |
| Additional Infomation |
CK1alpha/CDK7/CDK9 Inhibitor BTX-A51 is the ditosylated salt of A51, an orally bioavailable inhibitor of casein kinase 1alpha (CK1alpha) and cyclin-dependent kinases 7 and 9 (CDK7 and CDK9), with potential antineoplastic activity. Upon administration, BTX-A51 binds to and inhibits the activity of CK1alpha, CDK7, and CDK9. Blocking the phosphorylation and kinase activity of CK1alpha prevents the enhanced binding of murine double minute X (MDMX) to p53, the formation of CK1alpha and MDM2 complex, and the resulting inhibition of p53. This induces p53-mediated cell cycle arrest, slowing tumor cell proliferation. Blocking the phosphorylation and kinase activity of CDK7 and CDK9 prevents the positive transcription elongation factor b (PTEFb)-mediated activation of RNA polymerase II (RNA Pol II) and leads to the inhibition of gene transcription of various anti-apoptotic proteins. This also induces cell cycle arrest and apoptosis, slowing tumor cell proliferation. CK1alpha, a serine/threonine kinase and a leukemic stem cell target, acts as a tumor suppressor in several cancers through the negative regulation of Wnt/beta-catenin signaling and p53. It negatively regulates p53 by phosphorylating MDMX, thus enhancing binding of MDMX to p53, as well as by forming a complex with MDM2. CDK7, a serine/threonine kinase, plays a role in controlling cell cycle progression, transcriptional regulation, and promotes the expression of key oncogenes such as c-Myc through the phosphorylation of RNA Pol II. CDK9, also a serine/threonine kinase, regulates elongation of transcription through phosphorylation of RNA Pol II at serine 2 (p-Ser2-RNAPII). It is upregulated in various tumor cell types and plays a key role in the regulation of RNA Pol II-mediated transcription of anti-apoptotic proteins. Tumor cells are dependent on anti-apoptotic proteins for their survival.
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| Molecular Formula |
C18H25CLN6
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|---|---|
| Molecular Weight |
360.884301900864
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| Exact Mass |
360.182
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| CAS # |
2079068-74-7
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| PubChem CID |
126558497
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| Appearance |
Off-white to brown solid powder
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| LogP |
2.9
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
25
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| Complexity |
439
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1=CN=C(N=C1C1C=NN(C)C=1CC1CC1)NC1CCC(CC1)N
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| InChi Key |
RVZJFCNYSSUDCU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H25ClN6/c1-25-16(8-11-2-3-11)14(9-22-25)17-15(19)10-21-18(24-17)23-13-6-4-12(20)5-7-13/h9-13H,2-8,20H2,1H3,(H,21,23,24)
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| Chemical Name |
4-N-[5-chloro-4-[5-(cyclopropylmethyl)-1-methylpyrazol-4-yl]pyrimidin-2-yl]cyclohexane-1,4-diamine
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : 100 mg/mL (277.10 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.93 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.93 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.93 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7710 mL | 13.8550 mL | 27.7100 mL | |
| 5 mM | 0.5542 mL | 2.7710 mL | 5.5420 mL | |
| 10 mM | 0.2771 mL | 1.3855 mL | 2.7710 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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