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

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

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

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P271Use only outdoors or in a well-ventilated area.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P321Specific treatment (see … on this label).

P330Rinse mouth.

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P337+P313IF eye irritation persists: Get medical advice/attention.

P403+P233Store in a well-ventilated place. Keep container tightly closed.

P405Store locked up.

P501Dispose of contents/container to..…

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

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

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