N-(4-Piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide hydrochloride
N-(4-Piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide hydrochloride
CAS: 902135-91-5
Molecular Formula: C16H18Cl3N5O2
N-(4-Piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide hydrochloride - Names and Identifiers
| Name | N-(4-Piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide hydrochloride |
| Synonyms | CS-266 AT7519 AT 7519 AT-7519 AT-7519 AT-7519(HCl) AT 7519 HYDROCHLORIDE AT-7519 HYDROCHLORIDE AT7519 (Hydrochloride) 4-(2,6-Dichlorobenzamido)-N-(piperidin-4-yl)-1H-pyrazole-3-carboxamide HCl N-(4-piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide Hcl N-(4-piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide Hcl N-(4-Piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide hydrochloride |
| CAS | 902135-91-5 |
| InChI | 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 |
N-(4-Piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide hydrochloride - Physico-chemical Properties
| Molecular Formula | C16H18Cl3N5O2 |
| Molar Mass | 418.7 |
| Storage Condition | -20℃ |
| Use | AT7519 is a potent CDK inhibitor with IC50 values of 210,47,100,13,170 and <10 nM for CDK1,CDK2,CDK4-CDK6 and CDK9, respectively. |
| In vitro study | AT7519 is an ATP competitive CDK inhibitor with a K I value of 38 nM for Cdk1. AT7519 has no activity against all non-CDK kinases except GSK3β (IC50=89 nM). AT7519 exhibits potent antiproliferative activity in various human tumor cell lines with IC50 values ranging from 40 nM (for MCF-7) to 940 nM (for SW620), consistent with inhibition of CDK1 and cdk2. AT7519 induces dose-dependent cytotoxicity in multiple myeloma (MM) cell lines with IC50 values ranging from 0.5 to 2 μm at 48 h, the most sensitive cell line being MM.1s (0.5 μm) and U266 (0.5 μm), the most resistant was MM.1R (>2 μm). It does not induce cytotoxicity in peripheral blood mononuclear cells (PBMNC). AT7519 partially inhibits IL6 and IGF-1-induced proliferative dominance, as well as protective effects on bone marrow stromal cells (BMSCs). AT7519 induces rapid RNA pol II CTD dephosphorylation at serine 2 and serine 5 sites and leads to repression of transcription, partially contributing to at7519-induced cytotoxicity in MM cells. AT7519 induces GSK-3β activation by down-regulating GSK-3β phosphorylation, which also contributes to at7519-induced apoptosis independent of transcriptional repression. |
| In vivo study | In the HCT116 and HT29 colon cancer xenograft models, twice daily dosing of AT7519 (9.1 mg/kg) caused early and late subcutaneous tumor regression. In the human MM xenograft mouse model, AT7519 treatment (15 mg/kg) inhibited tumor growth and prolonged mean overall mouse survival, which was associated with increased caspase 3 activation. |
N-(4-Piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide hydrochloride - Reference
| Reference Show more | 1: Komiyama T, Kihara H, Hirose K, Yoshimoto R, Shigematsu H. AT-1015, a novel serotonin2A receptor antagonist, improves resaturation of exercised ischemic muscle in hypercholesterolemic rabbits. J Vasc Surg. 2004 Mar;39(3):661-7. PubMed PMID: 14981464. 2: Rashid M, Watanabe M, Nakazawa M, Nagatomo T. AT-1015, a newly synthesized 5-HT2 receptor antagonist, dissociates slowly from the 5-HT2 receptor sites in rabbit cerebral cortex membrane. J Pharm Pharmacol. 2002 Aug;54(8):1123-8. PubMed PMID: 12195828. 3: Rashid M, Watanabe M, Nakazawa M, Nakamura T, Hattori K, Nagatom T. Assessment of affinity and dissociation ability of a newly synthesized 5-HT2 antagonist, AT-101 5: comparison with other 5-HT2 antagonists. Jpn J Pharmacol. 2001 Nov;87(3):189-94. PubMed PMID: 11885967. 4: Kihara H, Koganei H, Hirose K, Yamamoto H, Yoshimoto R. Antithrombotic activity of AT-1015, a potent 5-HT(2A) receptor antagonist, in rat arterial thrombosis model and its effect on bleeding time. Eur J Pharmacol. 2001 Dec 21;433(2-3):157-62. PubMed PMID: 11755147. 5: Kihara H, Hirose K, Koganei H, Sasaki N, Yamamoto H, Kimura A, Nishimori T, Shoji M, Yoshimoto R. AT-1015, a novel serotonin (5-HT)2 receptor antagonist, blocks vascular and platelet 5-HT2A receptors and prevents the laurate-induced peripheral vascular lesion in rats. J Cardiovasc Pharmacol. 2000 Apr;35(4):523-30. PubMed PMID: 10774780. |
N-(4-Piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide hydrochloride - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 2.616 ml | 13.081 ml | 26.162 ml |
| 5 mM | 0.523 ml | 2.616 ml | 5.232 ml |
| 10 mM | 0.262 ml | 1.308 ml | 2.616 ml |
| 5 mM | 0.052 ml | 0.262 ml | 0.523 ml |
Last Update：2024-01-02 23:10:35
N-(4-Piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide hydrochloride - Reference Information
| biological activity | AT7519 HCl is a multiple CDK inhibitor that acts on CDK1,2,4,6 and 9, the IC50 in the cell-free assay was 10-210 nM. It has a weak effect on CDK3 and little activity on cdk7. Phase 2. |
| Target | Value |
| CDK9/CyclinT (Cell-free assay) | <10 nM |
| CDK5/p35 (Cell-free assay) | 13 nM |
| CDK2/CyclinA (Cell-free assay) | 47 nM |
| GSK-3β (Cell-free assay) | 89 nM |
| CDK4/CyclinD1 (Cell-free assay) | 100 nM |
Last Update：2024-04-10 22:41:03
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Product Name: 4-(2,6-Dichlorobenzoylamino)-1H-pyrazole-3-carboxylic Acid Piperidin-4-ylamide Monohydrochloride Visit Supplier Webpage Request for quotationCAS: 902135-91-5
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