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Details

Stereochemistry ACHIRAL
Molecular Formula C16H17Cl2N5O2
Molecular Weight 382.244
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AT-7519

SMILES

ClC1=CC=CC(Cl)=C1C(=O)NC2=CNN=C2C(=O)NC3CCNCC3

InChI

InChIKey=OVPNQJVDAFNBDN-UHFFFAOYSA-N
InChI=1S/C16H17Cl2N5O2/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)

HIDE SMILES / InChI

Description

AT7519 is an inhibitor of Cyclin-dependent kinases (CDK). AT7519 potently inhibited CDK1,CDK2,CDK4 to CDK6, and CDK9. The compound had lower potency against other CDKs tested (CDK3 and CDK7) and was inactive against all of the non-CDK kinases tested with the exception of GSK3beta. AT7519 showed potent antiproliferative activity in a panel of human tumor cell lines. AT7519 caused cell cycle arrest followed by apoptosis in human tumor cells and inhibited tumor growth in human tumor xenograft models. AT7519 is currently being investigated in Phase 1/2 studies.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
210.0 nM [IC50]
47.0 nM [IC50]
100.0 nM [IC50]
13.0 nM [IC50]
10.0 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown
Primary
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
459.3 ng/mL
21 mg/m² single, intravenous
AT-7519 plasma
Homo sapiens
508.7 ng/mL
21 mg/m² 2 times / week multiple, intravenous
AT-7519 plasma
Homo sapiens
591 ng/mL
27 mg/m² single, intravenous
AT-7519 plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
2300 ng × h/mL
21 mg/m² single, intravenous
AT-7519 plasma
Homo sapiens
2449 ng × h/mL
21 mg/m² 2 times / week multiple, intravenous
AT-7519 plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
11.1 h
21 mg/m² single, intravenous
AT-7519 plasma
Homo sapiens
10.7 h
21 mg/m² 2 times / week multiple, intravenous
AT-7519 plasma
Homo sapiens
13.1 h
27 mg/m² single, intravenous
AT-7519 plasma
Homo sapiens

Doses

AEs

Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer





Drug as perpetrator​

Drug as victim

PubMed

Sample Use Guides

In Vivo Use Guide
AT7519M: 27 mg/m2 IV injection, 1 hour infusion, 27 mg/m2/day twice weekly x 2 weeks every 3 weeks (days 1, 4, 8 and 11)
Route of Administration: Intravenous
In Vitro Use Guide
AT7519 showed potent antiproliferative activity (40-940 nmol/L) in a panel of human tumor cell lines, and the mechanism of action was shown here to be consistent with the inhibition of CDK1 and CDK2 in solid tumor cell lines. AT7519 caused cell cycle arrest followed by apoptosis in human tumor cells and inhibited tumor growth in human tumor xenograft models.