AG-24322

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H20F2N6
Molecular Weight	418.4419
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCNCC1=CN=CC(C2=CC3=C(NN=C3C4=NC5=C(F)C=C(F)C=C5N4)C=C2)=C1C

InChI

InChIKey=MEKASOQEXYKAKM-UHFFFAOYSA-N

InChI=1S/C23H20F2N6/c1-3-26-9-14-10-27-11-17(12(14)2)13-4-5-19-16(6-13)21(31-30-19)23-28-20-8-15(24)7-18(25)22(20)29-23/h4-8,10-11,26H,3,9H2,1-2H3,(H,28,29)(H,30,31)

HIDE SMILES / InChI

Molecular Formula	C23H20F2N6
Molecular Weight	418.4419
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://adisinsight.springer.com/drugs/800014124 | https://www.ncbi.nlm.nih.gov/pubmed/18509643

Agouron (Pfizer) was developing AG-24322 (AG-024322), a small-molecule cyclin-dependent kinase (CDK) inhibitor, for the treatment of cancer. AG-024322 is a potent inhibitor of CDK1, CDK2, and CDK4 that produces cell-cycle arrest and antitumor activity in preclinical models. AG-24322 is a potent ATP-competitive inhibitor of CDK1, CDK2, and CDK4 with Ki values in the 2–3 nM range and selectivity over other non-CDKs. This compound has been shown to inhibit Rb phosphorylation in cells, elicit cell-cycle arrest, and have antiproliferative activity in multiple human tumor cell lines (IC50 values from 30 to 200 nM). AG-24322 was reported to be undergoing phase I trials for cancer in the US, however the development was discontinued.

Originator

Approval Year

PubMed

Title	Date	PubMed
Toxicity and toxicokinetics of the cyclin-dependent kinase inhibitor AG-024322 in cynomolgus monkeys following intravenous infusion.	2008 Nov	18509643
Graphic rule for drug metabolism systems.	2010 May	20446902
Spectrum and Degree of CDK Drug Interactions Predicts Clinical Performance.	2016 Oct	27496135

Patents

Sample Use Guides

In Vivo Use Guide

Male and female monkeys received AG-024322 by 30-min IV infusion once daily for 5 days at doses of 2, 6, and 10 mg/kg (24, 72, and 120 mg/m(2), respectively). Doses were based upon the results of a dose range-finding study in monkeys; decreased white blood cells occurred at > or =3 mg/kg and 12 mg/kg produced central nervous system effects and was above the maximum-tolerated dose. The no-adverse-effect dose of AG-024322 was 2 mg/kg and associated with overall mean plasma AUC(0-24.5) of 2.11 ug h/mL.

Route of Administration: Intravenous

In Vitro Use Guide

AG-24322 is a potent ATP-competitive inhibitor of CDK1, CDK2, and CDK4 with Ki values in the 2–3 nM range and selectivity over other non-CDKs. This compound has been shown to inhibit Rb phosphorylation in cells, elicit cell-cycle arrest, and have antiproliferative activity in multiple human tumor cell lines (IC50 values from 30 to 200 nM).

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:35:40 UTC 2023` Edited by `admin` on `Fri Dec 15 15:35:40 UTC 2023`
Record UNII	926F8X7TNO
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AG-24322

Common Name

English

AG 024322 [WHO-DD]

Common Name

English

AG-024322

Code

English

3-PYRIDINEMETHANAMINE, 5-(3-(4,6-DIFLUORO-1H-BENZIMIDAZOL-2-YL)-1H-INDAZOL-5-YL)-N-ETHYL-4-METHYL-

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2185