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844442-38-2 (AT7519)



AT7519 AT7519
Name AT7519
Formula C16H17Cl2N5O2
MW 382.24
CAS No. 844442-38-2
Smiles O=C(NC1=CNN=C1C(NC2CCNCC2)=O)C3=C(Cl)C=CC=C3Cl
Synonyms AT 7519;AT-7519; 4-(2,6-dichlorobenzamido)-N-(piperidin-4-yl)-1H-pyrazole-3-carboxamide
InChI 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)


AT7519 is a multi-CDK inhibitor for CDK1, 2, 4, 6 and 9 with IC50 of 10-210 nM; less potent to CDK3 and little active to CDK7.

Background Information

A multi-CDK inhibitor for CDK1, 2, 4, 6 and 9 with IC50 of 10-210 nM. It is less potent to CDK3 and little active to CDK7 ......by AOBIOUS INC
AT7519 is a novel small molecule multi-cyclin-dependent kinase inhibitor.AT7519 displays potent cytotoxicity and apoptosis; associated with in vivo tumor growth inhibition and prolonged survival. At the molecular level, AT7519 inhibited RNA polymerase II (RNA pol II) phosphorylation, a CDK9, 7 substrate, associated with decreased RNA synthesis confirmed by [ (3)H] Uridine incorporation. In addition, AT7519 inhibited glycogen synthase kinase 3beta (GSK-3beta) phosphorylation. ......by AbMole BioScience
AT7519 is an inhibitor of multiple cyclin-dependent kinases (CDKs), which may result in cell cycle arrest, induction of apoptosis, and inhibition of tumor cell proliferation. ......by AdooQ BioScience, LLC
Description ......by Apexbio Technology LLC
AT-7519 is an orally bioavailable small molecule CDK inhibitor with potential antineoplastic activity. AT7519M selectively binds to and inhibits cyclin dependent kinases (CDKs), which may result in cell cycle arrest, induction of apoptosis, and inhibition ......by BOC Sciences
AT7519 as a potent inhibitor of CDKs, with IC50s of 210, 47, 100, 13, 170, and <10 nM for CDK1, CDK2, CDK4 to CDK6, and CDK9, respectively. ......by MedChemexpress Co., Ltd.
A potent CDK2 inhibitor with IC50 of 47 nM; also inhibits CDK1/4/5 with IC50 of 190/67/18 nM and shows selectivity over some kinases (Aurora A, IR kinase, MEK, PDK1, c-Abl, IC50>10 uM); has antiproliferative activity against HCT116 cells with IC50 of 82 nM; exhibits good profile against cytochrome P450 isoforms (<30% inhibition at 10 uM for 1A2, 2D6, 3A4, 2C9, 2C19).Blood CancerPhase 2 Clinical ......by ProbeChem
AT7519 is a multi-CDK inhibitor for CDK1, 2, 4, 6 and 9 with IC50 of 10-210 nM. It is less potent to CDK3 and little active to CDK7. Phase 2. ......by Selleck Chemicals LLC
AT7519 is a multi-CDK inhibitor for CDK1, 2, 4, 6 and 9 with IC50 of 10-210 nM. It is less potent to CDK3 and little active to CDK7. Phase 2. ......by Target Molecule Corp.

Protocol(Only for Reference)

Cell Experiment

Cell lines MM.1S, MM.1R, RPMI8226, U266, RPMI8266, RPMI-Dox40, OPM1 cells, primary MM cells and PBMNCs
Conditions Dissolved in DMSO at a concentration of 10 mM, final concentrations 0.25-4 μM; 24 or 48 hours
Method Cells are incubated with different concentrations of AT7519 for 24 or 48 hours at 37 °C. Cell viability is assessed by measuring 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrasodium bromide (MTT) dye absorbance. DNA synthesis is measured by tritiated thymidine uptake (3H-TdR). Apoptosis is assessed by using Annexin V/PI staining. The percentage of cells undergoing apoptosis is defined as the sum of early apoptosis (Annexin V-positive cells) and late apoptosis (Annexin V-positive and PI-positive cells
Source Selleck Chemicals LLC

Animal Experiment

Animal Models Male SCID mice inoculated subcutaneously with MM.1S cells
Dosage 15 mg/kg/day
Formulation Dissolved in 0.9% saline
Administration Dosed i.p.
Source Selleck Chemicals LLC

Physical and Chemical Properties

Appearance:White to off-white solid EBNumber:EB000029148

Storage condition


DMSO ≥22mg/mL Water <1.2mg/mL Ethanol <1.2mg/mL by MedChemexpress Co., Ltd.
(25°C) * In vitro DMSO 10 mg/mL (26.16 mM); Water<1 mg/mL (<1 mM); Ethanol<1 mg/mL (<1 mM); In vivo 30% Propylene glycol, 5% Tween 80, 65% D5W30 mg/mL by Selleck Chemicals LLC

Mechanism and Indication


Clinical Information

Product Name Sponsor & Collaborators Indications Start Date End Date Phase
AT7519 NCIC Clinical Trials Group Mantle cell lymphoma 2012/8/31 2015/2/28 Phase 2 Clinical
AT7519 NCIC Clinical Trials Group Chronic lymphocytic leukemia 2012/8/31 2014/7/31 Phase 2 Clinical
AT7519 Astex Therapeutics Ltd Multiple myeloma 2010/11/30 2014/10/31 Phase 2 Clinical
AT7519 National Cancer Institute of Canada Solid tumor 2006/8/31 2013/1/1 Phase 1 Clinical
AT7519 National Cancer Institute of Canada Solid tumor 2006/8/31 2013/1/1 Phase 1 Clinical
AT7519 National Cancer Institute of Canada Non-Hodgkin lymphoma 2006/8/31 2013/1/1 Phase 1 Clinical
AT7519 - Phase 2

Safety Data of AT7519


Spectral Information


Suppliers List

Company Price and Availability Country/Region
AbMole BioScience USA
AdooQ BioScience, LLC USA
Apexbio Technology LLC USA
Ark Pharm, Inc. USA
BOC Sciences
Biochempartner Co., Ltd China
CHEMSCENE, LLC 5mg/USD60();10mg/USD90() USA
MedChemexpress Co., Ltd. 5mg/USD60();10mg/USD90() USA
Selleck Chemicals LLC 5mg/USD110(In stock);10mM/1mLIn DMSO/USD170(In stock);10mg/USD210(In stock);25mg/USD370(In stock);100mg/USD1170(In stock) USA
Shanghai Haoyuan Chemexpress Co., Ltd. 5mg/USD60();10mg/USD90() China
Target Molecule Corp. 5mg/USD94();10mg/USD134();25mg/USD242();50mg/USD372() USA

Related Products

Other Forms of 844442-38-2

Name CAS No Formula MW
AT7519 (trifluoroacetate) 1431697-85-6 C18H18Cl2F3N5O4 496.27
AT7519 (Hydrochloride) 902135-91-5 C16H18Cl3N5O2 418.71

Recommended Compounds in CDK

Name CAS No Formula MW
LY2857785 1619903-54-6 C26H36N6O 448.6
THZ2 1604810-84-5 C31H28ClN7O2 566.0527
Palbociclib (isethionate) 827022-33-3 C26H35N7O6S 573.66
CDK9-IN-6 1391855-95-0 C27H37ClN6O2 513.07468
ML167 1285702-20-6 C19H17N3O3 335.36
AMG 925 1401033-86-0 C26H29N7O2 471.55
LDC000067 1073485-20-7 C18H18N4O3S 370.43
LEE011 (succinate hydrate) 1374639-79-8 C27H38N8O6X 570.64
LEE011 (succinate) 1374639-75-4 C27H36N8O5 552.63
LEE011 (hydrochloride) 1211443-80-9 C23H31ClN8O 471.0
LEE011 1211441-98-3 C23H30N8O 434.54
WHI-P180 (hydrochloride) 153437-55-9 C16H16ClN3O3 333.77
Wogonin 632-85-9 C16H12O5 284.26
1-NM-PP1 221244-14-0 C20H21N5 331.41
WHI-P180 211555-08-7 C16H15N3O3 297.31
THZ1 1604810-83-4 C31H28ClN7O2 566.05
Senexin A 1366002-50-7 C17H14N4 274.32
CDK4-IN-1 1256963-02-6 C22H29ClN8 440.97
Palbociclib (hydrochloride) 827022-32-2 C24H30ClN7O2 483.99
Purvalanol B 212844-54-7 C20H25ClN6O3 432.9

Recommended Compounds in Same Indication

Name CAS No Formula MW
AZD1152 722543-31-9 C26H31FN7O6P 587.54
Mocetinostat 726169-73-9 C23H20N6O 396.44
CAL-101 870281-82-6 C22H18FN7O 415.42
PU-H71 873436-91-0 C18H21IN6O2S 512.37
BMS-599626 (Hydrochloride) 873837-23-1 C27H28ClFN8O3 567.01
Quisinostat 875320-29-9 C21H26N6O2 394.4702
AT9283 896466-04-9 C19H23N7O2 381.43
KX2-391 897016-82-9 C26H29N3O3 431.53
SNX-2112 908112-43-6 C23H27F3N4O3 464.48
MLN9708 1239908-20-3 C20H23BCl2N2O9 517.12
Panobinostat 404950-80-7 C21H23N3O2 349.43
Nordihydroguaiaretic acid 500-38-9 C18H22O4 302.36
Pazopanib (Hydrochloride) 635702-64-6 C21H24ClN7O2S 473.98
RX-3117 865838-26-2 C10H12FN3O4 257.22
N-Hydroxy-3-(3-phenylsulfamoylphenyl)acrylamide 414864-00-9 C15H14N2O4S 318.34766
Carfilzomib 868540-17-4 C40H57N5O7 719.91
FK866 658084-64-1 C24H29N3O2 391.51
OSU-03012 742112-33-0 C26H19F3N4O 460.45
Motesanib (Diphosphate) 857876-30-3 C22H29N5O9P2 569.44
LY2603618 911222-45-2 C18H22BrN5O3 436.3

Route of Synthesis



[1]. Santo L, Vallet S, Hideshima T, Cirstea D, Ikeda H, Pozzi S, Patel K, Okawa Y, Gorgun G, Perrone G, Calabrese E, Yule M, Squires M, Ladetto M, Boccadoro M, Richardson PG, Munshi NC, Anderson KC, Raje N.AT7519, A novel small molecule multi-cyclin-dependent kinase inhibitor, induces apoptosis in multiple myeloma via GSK-3beta activation and RNA polymerase II inhibition.Oncogene. 2010 Apr 22;29(16):2325-36. Epub 2010 Jan 25.

[2]. Squires MS, Feltell RE, Wallis NG, Lewis EJ, Smith DM, Cross DM, Lyons JF, Thompson NT.Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines.Mol Cancer Ther. 2009 Feb;8(2):324-32. Epub 2009 Jan 27.

[3]. Squires MS, Cooke L, Lock V, Qi W, Lewis EJ, Thompson NT, Lyons JF, Mahadevan D.AT7519, a cyclin-dependent kinase inhibitor, exerts its effects by transcriptional inhibition in leukemia cell lines and patient samples.Mol Cancer Ther. 2010 Apr;9(4):920-8. Epub 2010 Mar 30.

[4]. Mahadevan D, Plummer R, Squires MS, Rensvold D, Kurtin S, Pretzinger C, Dragovich T, Adams J, Lock V, Smith DM, Von Hoff D, Calvert H.A phase I pharmacokinetic and pharmacodynamic study of AT7519, a cyclin-dependent kinase inhibitor in patients with refractory solid tumors.Ann Oncol. 2011 Sep;22(9):2137-43. Epub 2011 Feb 16.

[5]. Wyatt PG, Woodhead AJ, Berdini V, Boulstridge JA, Carr MG, Cross DM, Davis DJ, Devine LA, Early TR, Feltell RE, Lewis EJ, McMenamin RL, Navarro EF, O'Brien MA, O'Reilly M, Reule M, Saxty G, Seavers LC, Smith DM, Squires MS, Trewartha G, Walker MT, Woolford AJ.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.J Med Chem. 2008 Aug 28;51(16):4986-99. Epub 2008 Jul 26.

Protocol Reference


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