ChemicalBook Product Catalog Biochemical Engineering Biochemical Reagents Agonist Inhibitors N-(4-piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide Hcl

N-(4-piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide Hcl

Product NameN-(4-piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide Hcl
CAS902135-91-5
MFC16H18Cl3N5O2
MW418.7
EINECS
MOL File902135-91-5.mol

Chemical Properties

storage temp.	Store at -20°C
solubility	≥29.93 mg/mL in H2O; ≥43.3 mg/mL in DMSO with ultrasonic; ≥8.82 mg/mL in EtOH with ultrasonic
form	crystalline solid
color	White to off-white
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
InChIKey	PAOFPNGYBWGKCO-UHFFFAOYSA-N
SMILES	N(C1=CNN=C1C(=O)NC1CCNCC1)C(C1C(=CC=CC=1Cl)Cl)=O.Cl

Usage And Synthesis

Description

AT7519 is an ATP-competitive inhibitor of cyclin-dependent kinases (Cdks) with IC₅₀ values of 210, 47, 100, 13, 170, and <10 nM for Cdk1, 2, 4, 5, 6, and 9, respectively. It is less potent against Cdk3 and Cdk7 and inactive against non-Cdk kinases save for GSK3β (IC₅₀ = 89 nM). AT7519 demonstrates antiproliferative activity against a wide variety of human tumor cell lines (IC₅₀s = 40-940 nM in vitro), inhibiting cell cycle progression and inducing apoptosis, and prevents tumor growth in human tumor xenograft models. AT7519 induces activation of GSK3β by down-regulating GSK3β phosphorylation, which contributes to AT7519-induced apoptosis.

Uses

4-(2,6-DichlorobenzoylaMino)-1H-pyrazole-3-carboxylic Acid Piperidin-4-ylaMide Monohydrochloride is used in the structure based design of a cyclin-dependant kinase CDK2 inhibitor.

Uses

4-(2,6-Dichlorobenzoylamino)-1H-pyrazole-3-carboxylic Acid Piperidin-4-ylamide is used in the structure based design of a cyclin-dependant kinase CDK2 inhibitor.

in vivo

AT7519 inhibits tumor growth in a human MM xenograft mouse model^[1]. AT7519 (4.6 and 9.1 mg/kg/dose) inhibits the growth of early-stage HCT116 tumor xenografts. AT7519 (10 mg/kg, i.p.) also inhibits the target CDKs in HCT116 tumor-bearing BALB/c nude mice^[2].

IC 50

CDK9/Cyclin T: 10 nM (IC₅₀); CDK5/p35: 13 nM (IC₅₀); cdk2/cyclin A: 47 nM (IC₅₀); Cdk4/cyclin D1: 100 nM (IC₅₀); cdk6/cyclin D3: 170 nM (IC₅₀); Cdk1/cyclin B: 210 nM (IC₅₀); CDK7/Cyclin H/MAT1: 2400 nM (IC₅₀); GSK3β: 89 nM (IC₅₀)

References

[1] MATTHEW S SQUIRES. Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines.[J]. Molecular Cancer Therapeutics, 2009, 8 2: 324-332. DOI: 10.1158/1535-7163.mct-08-0890
[2] L SANTO. AT7519, A novel small molecule multi-cyclin-dependent kinase inhibitor, induces apoptosis in multiple myeloma via GSK-3β activation and RNA polymerase II inhibition[J]. Oncogene, 2010, 29 16: 2325-2336. DOI: 10.1038/onc.2009.510

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