AT-7519 MESYLATE

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C16H17Cl2N5O2.CH4O3S
Molecular Weight	478.35
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=UELIMKCXGLIYCY-UHFFFAOYSA-N

InChI=1S/C16H17Cl2N5O2.CH4O3S/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;1-5(2,3)4/h1-3,8-9,19H,4-7H2,(H,20,23)(H,21,25)(H,22,24);1H3,(H,2,3,4)

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

Molecular Formula	CH4O3S
Molecular Weight	96.106
Charge	0
Count

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19174555 | https://astx.com/research-development/clinical-pipeline/at7519-cdk-inhibitor-solid-tumors/https://www.ncbi.nlm.nih.gov/pubmed/27750483 | https://clinicaltrials.gov/ct2/show/NCT01627054

AT7519M or AT7519, a small molecule inhibitor of cyclin-dependent kinases 1, 2, 4, 5, and 9, participated in phase II clinical trials in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). As a result, in CLL, some patients had tumor reductions, but the objective response rate (ORR) was low. In MCL, activity was noted with ORR of 27%. In addition, AT7519M was studied in patients with previously treated multiple myeloma, to understand whether the drug alone or in combination with bortezomib were effective treatments. Recent experiments also have shown that AT7519 is a promising drug for the treatment of high-risk neuroblastoma patients with MYCN amplification. It is known, that MYCN-dependent neuroblastomas have low cure rates with current multimodal treatment.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Cyclin-dependent kinase 1 27 Target ID: CHEMBL308 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19174555	Inhibitor 8504	210.0 nM [IC50]
Cyclin-dependent kinase 2 23 Target ID: CHEMBL301 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19174555	Inhibitor 8504	47.0 nM [IC50]
Cyclin-dependent kinase 4 26 Target ID: CHEMBL331 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19174555	Inhibitor 8504	100.0 nM [IC50]
Cyclin-dependent kinase 6 16 Target ID: CHEMBL2508 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19174555	Inhibitor 8504	13.0 nM [IC50]
Cyclin-dependent kinase 9 24 Target ID: CHEMBL3116 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19174555	Inhibitor 8504	10.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Chronic lymphocytic leukemia 59 Sources: http://adisinsight.springer.com/drugs/800023173	Primary	Phase II 1147	Unknown Approved Use Unknown
Multiple myeloma 159 Sources: http://adisinsight.springer.com/drugs/800023173	Primary	Phase II 1147	Unknown Approved Use Unknown
Mantle cell lymphoma 24 Sources: http://adisinsight.springer.com/drugs/800023173	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
591 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25393368	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
508.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33095286	21 mg/m² 2 times / week multiple, intravenous dose: 21 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: ONALESPIB	ONALESPIB	AT-7519 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
459.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33095286	21 mg/m² single, intravenous dose: 21 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: ONALESPIB	ONALESPIB	AT-7519 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
591 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25393368	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

Value	Dose	Co-administered	Analyte	Population
2449 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33095286	21 mg/m² 2 times / week multiple, intravenous dose: 21 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: ONALESPIB	ONALESPIB	AT-7519 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2300 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33095286	21 mg/m² single, intravenous dose: 21 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: ONALESPIB	ONALESPIB	AT-7519 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
13.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25393368	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
10.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33095286	21 mg/m² 2 times / week multiple, intravenous dose: 21 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: ONALESPIB	ONALESPIB	AT-7519 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
11.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33095286	21 mg/m² single, intravenous dose: 21 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: ONALESPIB	ONALESPIB	AT-7519 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
13.1 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25393368	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

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/25393368	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25393368	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: https://pubmed.ncbi.nlm.nih.gov/25393368
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: https://pubmed.ncbi.nlm.nih.gov/25393368	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25393368	DLT: Mucositis... Dose limiting toxicities: Mucositis (grade 3, 6.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/25393368

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/25393368	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25393368
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: https://pubmed.ncbi.nlm.nih.gov/25393368	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25393368
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: https://pubmed.ncbi.nlm.nih.gov/25393368	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25393368
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: https://pubmed.ncbi.nlm.nih.gov/25393368	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25393368
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: https://pubmed.ncbi.nlm.nih.gov/25393368	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25393368

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2C19 2057	BCRP 697 P-gp 2052 MRP1 113

Drug as perpetrator

Target	Modality	Activity
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/18656911/	weak [Inhibition 10 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/18656911/	weak [Inhibition 10 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/18656911/	weak [Inhibition 10 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/18656911/	weak [Inhibition 10 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/18656911/	weak [Inhibition 10 uM]

Drug as victim

Target	Modality	Activity
MRP1 113	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/25986678/	no
BCRP 697	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/31515284/	weak
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/31515284/	yes

PubMed

Title	Date	PubMed
Inhibition of cyclin-dependent kinases by AT7519 is effective to overcome chemoresistance in colon and cervical cancer.	2019-06-04	30979499
Anticancer and radiosensitizing effects of the cyclin-dependent kinase inhibitors, AT7519 and SNS‑032, on cervical cancer.	2018-08	29901072
The cyclin-dependent kinase inhibitor AT7519 accelerates neutrophil apoptosis in sepsis-related acute respiratory distress syndrome.	2017-02	27965411
Cyclin-Dependent Kinase Inhibitor AT7519 as a Potential Drug for MYCN-Dependent Neuroblastoma.	2015-11-15	26202950
A Phase I study of cyclin-dependent kinase inhibitor, AT7519, in patients with advanced cancer: NCIC Clinical Trials Group IND 177.	2014-12-09	25393368
Comprehensive analysis of kinase inhibitor selectivity.	2011-10-30	22037378
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.	2010-11-24	21095574
AT7519, A novel small molecule multi-cyclin-dependent kinase inhibitor, induces apoptosis in multiple myeloma via GSK-3beta activation and RNA polymerase II inhibition.	2010-04-22	20101221
AT7519, a cyclin-dependent kinase inhibitor, exerts its effects by transcriptional inhibition in leukemia cell lines and patient samples.	2010-04	20354122
Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines.	2009-02	19174555
Identification of N-(4-piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide (AT7519), a novel cyclin dependent kinase inhibitor using fragment-based X-ray crystallography and structure based drug design.	2008-08-28	18656911

Patents

Sample Use Guides

In Vivo Use Guide

A Phase II study of AT7519M, a CDK Inhibitor, in Patients With Relapsed and/or Refractory Chronic Lymphocytic Leukemia. Dose: 27 mg/m2, IV injection, 1 hour infusion. Schedule: 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.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:09:16 GMT 2025` Edited by `admin` on `Mon Mar 31 18:09:16 GMT 2025`
Record UNII	Z239O75N33
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AT7519M

Preferred Name

English

AT-7519 MESYLATE

Common Name

English

AT-7519M

Common Name

English

1H-PYRAZOLE-3-CARBOXAMIDE, 4-((2,6-DICHLOROBENZOYL)AMINO)-N-4-PIPERIDINYL-, METHANESULPHONATE (1:1)

Systematic Name

English

4-((2,6-DICHLOROBENZOYL)AMINO)-N-PIPERIDIN-4-YL-1H-PYRAZOLE-3-CARBOXAMIDE METHANESULFONATE

Systematic Name

English

AT 7519M [WHO-DD]

Common Name

English

4-((2,6-DICHLOROBENZOYL)AMINO)-1H-PYRAZOLE-3-CARBOXIC ACIDE PIPERIDIN-4-YLAMIDE MESILATE SALT

Common Name

English

Code System Code Type Description

PUBCHEM

23657720

Created by admin on Mon Mar 31 18:09:16 GMT 2025 , Edited by admin on Mon Mar 31 18:09:16 GMT 2025

PRIMARY

FDA UNII

Z239O75N33

Created by admin on Mon Mar 31 18:09:16 GMT 2025 , Edited by admin on Mon Mar 31 18:09:16 GMT 2025

PRIMARY

SMS_ID

100000175617

Created by admin on Mon Mar 31 18:09:16 GMT 2025 , Edited by admin on Mon Mar 31 18:09:16 GMT 2025

PRIMARY

CAS

902135-89-1

Created by admin on Mon Mar 31 18:09:16 GMT 2025 , Edited by admin on Mon Mar 31 18:09:16 GMT 2025

PRIMARY

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AT-7519

ACTIVE MOIETY

Details

SMILES

InChI

DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/19174555 | https://astx.com/research-development/clinical-pipeline/at7519-cdk-inhibitor-solid-tumors/https://www.ncbi.nlm.nih.gov/pubmed/27750483 | https://clinicaltrials.gov/ct2/show/NCT01627054

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Approved Use

Approved Use

Cmax

AUC

T1/2

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

PubMed

Patents

Sample Use Guides

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19174555 | https://astx.com/research-development/clinical-pipeline/at7519-cdk-inhibitor-solid-tumors/https://www.ncbi.nlm.nih.gov/pubmed/27750483 | https://clinicaltrials.gov/ct2/show/NCT01627054

C_max

T_1/2

Drug as perpetrator