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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 of AG-24322

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

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.

Approval Year

PubMed

PubMed

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

Patents

Sample Use Guides

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
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 GMT 2023
Edited
by admin
on Fri Dec 15 15:35:40 GMT 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
Created by admin on Fri Dec 15 15:35:40 GMT 2023 , Edited by admin on Fri Dec 15 15:35:40 GMT 2023
Code System Code Type Description
CAS
837364-57-5
Created by admin on Fri Dec 15 15:35:40 GMT 2023 , Edited by admin on Fri Dec 15 15:35:40 GMT 2023
PRIMARY
PUBCHEM
135413565
Created by admin on Fri Dec 15 15:35:40 GMT 2023 , Edited by admin on Fri Dec 15 15:35:40 GMT 2023
PRIMARY
ChEMBL
CHEMBL3545420
Created by admin on Fri Dec 15 15:35:40 GMT 2023 , Edited by admin on Fri Dec 15 15:35:40 GMT 2023
PRIMARY
DRUG BANK
DB13035
Created by admin on Fri Dec 15 15:35:40 GMT 2023 , Edited by admin on Fri Dec 15 15:35:40 GMT 2023
PRIMARY
SMS_ID
300000042380
Created by admin on Fri Dec 15 15:35:40 GMT 2023 , Edited by admin on Fri Dec 15 15:35:40 GMT 2023
PRIMARY
NCI_THESAURUS
C52182
Created by admin on Fri Dec 15 15:35:40 GMT 2023 , Edited by admin on Fri Dec 15 15:35:40 GMT 2023
PRIMARY NCIT
FDA UNII
926F8X7TNO
Created by admin on Fri Dec 15 15:35:40 GMT 2023 , Edited by admin on Fri Dec 15 15:35:40 GMT 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
TARGET -> INHIBITOR
IC50
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY