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| 100mg |
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AT-7519 diHCl is a novel and potent multi-CDK (cyclin-dependent kinase) inhibitor for Cdk1/cyclin B, Cdk2/Cyclin A, Cdk3/Cyclin E, Cdk4/Cyclin D1, Cdk5/p35, and Cdk6/Cyclin D3 with IC50s of 210, 47, 100, 13, 170, and<10 nM for CDK1, CDK2, CDK4 to CDK6, and CDK9, respectively. All non-Cdk kinases except GSK3β are inactive against AT7519, an ATP competitive Cdk inhibitor. Many human tumor cell lines, including SW620, exhibit strong antiproliferative activity in response to AT7519. Regardless of transcription inhibition, AT7519 induces apoptosis through downregulating GSK-3β phosphorylation, which in turn activates GSK-3β.
| Targets |
CDK9/Cyclin T (IC50 = 10 nM); CDK5/p35 (IC50 = 13 nM); cdk2/cyclin A (IC50 = 47 nM); Cdk4/cyclin D1 (IC50 = 100 nM); cdk6/cyclin D3 (IC50 = 170 nM); Cdk1/cyclin B (IC50 = 210 nM); CDK7/Cyclin H/MAT1 (IC50 = 2400 nM); GSK3β (IC50 = 89 nM)
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| ln Vitro |
In MM cells, AT7519 Hydrochloride (0–4 μM) causes dose-dependent cytotoxicity with an IC50 range from 0.5–2 μM. This cytotoxicity is linked to GSK-3β activation and is not reliant on inflection point blockage. Time-induced induction of MM cells is achieved by AT7519 Hydrochloride (0.5 μM). Additionally, in MM.1S cells, AT7519 Hydrochloride (0.5 μM) partially inhibits RNA production and prevents RNA polymerase II CTD from being phosphorylated [1]. Human tumor cell lines' cell cycle progression is inhibited by AT7519 hydrochloric acid (250 nM). Human tumor cell lines likewise develop liver cancer when exposed to AT7519 hydrochloric acid [2]. Cellular effects are induced in blank cell lines by AT7519 hydrochloric acid (100-700 nM). In human tumor cell lines, AT7519 hydrochloride also suppresses transcription. Furthermore, RNA polymerase II is inhibited and antioxidant protein levels are decreased by AT7519 Hydrochronide [3].
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| ln Vivo |
In a human MM xenograft model, AT7519 hydrochloride suppresses the growth of tumors [1]. Early-stage HCT116 tumor xenografts are inhibited in their growth by AT7519 hydrochloride (4.6 and 9.1 mg/kg/dose). Target CDKs are likewise inhibited by AT7519 Hydrochloride (10 mg/kg, ip) in BALB/c nude mice with HCT116 tumors[2].
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| References |
[1]. Santo L, et al. AT7519, A novel small molecule multi-cyclin-dependent kinase inhibitor, induces apoptosis in multiple myeloma via GSK-3beta activation and RNA polymerase II inhibition. Oncogene. 2010 Apr 22;29(16):2325-36.
[2]. Squires MS, et al. Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines. Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines. [3]. Squires MS, et al. AT7519, a cyclin-dependent kinase inhibitor, exerts its effects by transcriptional inhibition in leukemia cell lines and patient samples. Mol Cancer Ther. 2010 Apr;9(4):920-8 |
| Molecular Formula |
C16H18CL3N5O2
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|---|---|
| Molecular Weight |
418.71
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| Exact Mass |
417.052608
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| Elemental Analysis |
C, 45.90; H, 4.33; Cl, 25.40; N, 16.73; O, 7.64
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| CAS # |
902135-91-5
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| Related CAS # |
AT7519;844442-38-2;AT7519 TFA;1431697-85-6
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| Appearance |
white solid powder
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| SMILES |
C1CNCCC1NC(=O)C2=C(C=NN2)NC(=O)C3=C(C=CC=C3Cl)Cl.Cl
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| InChi Key |
PAOFPNGYBWGKCO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H17Cl2N5O2.ClH/c17-10-2-1-3-11(18)13(10)15(24)22-12-8-20-23-14(12)16(25)21-9-4-6-19-7-5-9;/h1-3,8-9,19H,4-7H2,(H,20,23)(H,21,25)(H,22,24);1H
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| Chemical Name |
4-[(2,6-dichlorobenzoyl)amino]-N-piperidin-4-yl-1H-pyrazole-5-carboxamide;hydrochloride
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| Synonyms |
AT-7519 diHCl; AT7519; AT 7519; AT-7519
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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: ~52 mg/mL (~124.2 mM)
Ethanol: ~28 mg/mL (~66.9 mM) Water: ~43 mg/mL (~102.7 mM) |
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| Solubility (In Vivo) |
Saline: 30mg/mL (Please use freshly prepared in vivo formulations for optimal results.)
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3883 mL | 11.9414 mL | 23.8829 mL | |
| 5 mM | 0.4777 mL | 2.3883 mL | 4.7766 mL | |
| 10 mM | 0.2388 mL | 1.1941 mL | 2.3883 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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