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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

Molecular Formula C16H17Cl2N5O2
Molecular Weight 382.244
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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

Curator's Comment: Preclinical studies in female NMRI homozygous (nu/nu) mice with neuroblastoma patient-derived MYCN-amplified AMC711T xenografts revealed dose-dependent growth inhibition, which correlated with intratumoral AT7519 levels. No human data available.

Approval Year

Targets

Targets

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

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
459.3 ng/mL
21 mg/m² single, intravenous
dose: 21 mg/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered: ONALESPIB
AT-7519 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
508.7 ng/mL
21 mg/m² 2 times / week multiple, intravenous
dose: 21 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered: ONALESPIB
AT-7519 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
591 ng/mL
27 mg/m² single, intravenous
dose: 27 mg/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered:
AT-7519 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2300 ng × h/mL
21 mg/m² single, intravenous
dose: 21 mg/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered: ONALESPIB
AT-7519 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2449 ng × h/mL
21 mg/m² 2 times / week multiple, intravenous
dose: 21 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered: ONALESPIB
AT-7519 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
11.1 h
21 mg/m² single, intravenous
dose: 21 mg/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered: ONALESPIB
AT-7519 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
10.7 h
21 mg/m² 2 times / week multiple, intravenous
dose: 21 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered: ONALESPIB
AT-7519 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
13.1 h
27 mg/m² single, intravenous
dose: 27 mg/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered:
AT-7519 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
32.4 mg/m2 4 times / 3 weeks multiple, intravenous
MTD
Dose: 32.4 mg/m2, 4 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 32.4 mg/m2, 4 times / 3 weeks
Sources: Page: p.2264
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources: Page: p.2264
DLT: Fatigue, Febrile neutropenia...
Dose limiting toxicities:
Fatigue (grade 3, 20%)
Febrile neutropenia (grade 3, 20%)
Hypokalemia (grade 3, 20%)
Mucositis (grade 3, 20%)
Sources: Page: p.2264
27 mg/m2 4 times / 3 weeks multiple, intravenous
RP2D
Dose: 27 mg/m2, 4 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 27 mg/m2, 4 times / 3 weeks
Sources: Page: p.2264
unhealthy, ADULT
n = 15
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 15
Sources: Page: p.2264
DLT: Mucositis...
Dose limiting toxicities:
Mucositis (grade 3, 6.7%)
Sources: Page: p.2264
AEs

AEs

AESignificanceDosePopulation
Fatigue grade 3, 20%
DLT
32.4 mg/m2 4 times / 3 weeks multiple, intravenous
MTD
Dose: 32.4 mg/m2, 4 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 32.4 mg/m2, 4 times / 3 weeks
Sources: Page: p.2264
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources: Page: p.2264
Febrile neutropenia grade 3, 20%
DLT
32.4 mg/m2 4 times / 3 weeks multiple, intravenous
MTD
Dose: 32.4 mg/m2, 4 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 32.4 mg/m2, 4 times / 3 weeks
Sources: Page: p.2264
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources: Page: p.2264
Hypokalemia grade 3, 20%
DLT
32.4 mg/m2 4 times / 3 weeks multiple, intravenous
MTD
Dose: 32.4 mg/m2, 4 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 32.4 mg/m2, 4 times / 3 weeks
Sources: Page: p.2264
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources: Page: p.2264
Mucositis grade 3, 20%
DLT
32.4 mg/m2 4 times / 3 weeks multiple, intravenous
MTD
Dose: 32.4 mg/m2, 4 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 32.4 mg/m2, 4 times / 3 weeks
Sources: Page: p.2264
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources: Page: p.2264
Mucositis grade 3, 6.7%
DLT
27 mg/m2 4 times / 3 weeks multiple, intravenous
RP2D
Dose: 27 mg/m2, 4 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 27 mg/m2, 4 times / 3 weeks
Sources: Page: p.2264
unhealthy, ADULT
n = 15
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 15
Sources: Page: p.2264
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Other InhibitorOther SubstrateOther Inducer





Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
weak [Inhibition 10 uM]
weak [Inhibition 10 uM]
weak [Inhibition 10 uM]
weak [Inhibition 10 uM]
weak [Inhibition 10 uM]
Drug as victim
PubMed

PubMed

TitleDatePubMed
Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines.
2009 Feb
Patents

Sample Use Guides

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
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.
Substance Class Chemical
Created
by admin
on Sat Dec 16 01:48:17 GMT 2023
Edited
by admin
on Sat Dec 16 01:48:17 GMT 2023
Record UNII
X1BF92PW9T
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AT-7519
Common Name English
1H-PYRAZOLE-3-CARBOXAMIDE, 4-((2,6-DICHLOROBENZOYL)AMINO)-N-4-PIPERIDINYL
Common Name English
CDKI AT7519
Common Name English
AT 7519
Code English
4-(2,6-DICHLORO-BENZOYLAMINO)-1H-PYRAZOLE-3-CARBOXYLIC ACID PIPERIDIN-4-YLAMIDE
Systematic Name English
AT7519
Code English
4-(2,6-DICHLOROBENZOYLAMINO)-1H-PYRAZOLE-3-CARBOXYLIC ACID N-(PIPERIDIN-4-YL)AMIDE
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C2185
Created by admin on Sat Dec 16 01:48:17 GMT 2023 , Edited by admin on Sat Dec 16 01:48:17 GMT 2023
NCI_THESAURUS C129825
Created by admin on Sat Dec 16 01:48:17 GMT 2023 , Edited by admin on Sat Dec 16 01:48:17 GMT 2023
Code System Code Type Description
EPA CompTox
DTXSID30233420
Created by admin on Sat Dec 16 01:48:17 GMT 2023 , Edited by admin on Sat Dec 16 01:48:17 GMT 2023
PRIMARY
NCI_THESAURUS
C64761
Created by admin on Sat Dec 16 01:48:17 GMT 2023 , Edited by admin on Sat Dec 16 01:48:17 GMT 2023
PRIMARY NCIT
DRUG BANK
DB08142
Created by admin on Sat Dec 16 01:48:17 GMT 2023 , Edited by admin on Sat Dec 16 01:48:17 GMT 2023
PRIMARY
FDA UNII
X1BF92PW9T
Created by admin on Sat Dec 16 01:48:17 GMT 2023 , Edited by admin on Sat Dec 16 01:48:17 GMT 2023
PRIMARY
CAS
844442-38-2
Created by admin on Sat Dec 16 01:48:17 GMT 2023 , Edited by admin on Sat Dec 16 01:48:17 GMT 2023
PRIMARY
ChEMBL
CHEMBL445813
Created by admin on Sat Dec 16 01:48:17 GMT 2023 , Edited by admin on Sat Dec 16 01:48:17 GMT 2023
PRIMARY
PUBCHEM
11338033
Created by admin on Sat Dec 16 01:48:17 GMT 2023 , Edited by admin on Sat Dec 16 01:48:17 GMT 2023
PRIMARY
SMS_ID
300000038547
Created by admin on Sat Dec 16 01:48:17 GMT 2023 , Edited by admin on Sat Dec 16 01:48:17 GMT 2023
PRIMARY
CHEBI
91326
Created by admin on Sat Dec 16 01:48:17 GMT 2023 , Edited by admin on Sat Dec 16 01:48:17 GMT 2023
PRIMARY
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