General
Preferred name
AT-7519
Synonyms
AT7519 ()
AT7519 HCl ()
AT 7519 hydrochloride salt ()
AT 7519 mesylate ()
AT7519 (TFA) ()
AT7519 (Hydrochloride) ()
AT7519M ()
AT7519M (TFA) ()
AT7519 trifluoroacetate ()
AT7519 Hydrochloride ()
CDKI AT7519 ()
AT 7519 ()
P&D ID
PD004706
CAS
844442-38-2
902135-91-5
1431697-85-6
902135-89-1
Tags
available
drug candidate
Drug indication
Mantle cell lymphoma
Solid tumour/cancer
Drug Status
investigational
Max Phase
2.0
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
DESCRIPTION
AT7519 Hydrochloride is 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.
PRICE
70
INDICATION
Investigated for use/treatment in leukemia (unspecified), lymphoma (unspecified), myelodysplastic syndrome, and solid tumors.
MOA
AT7519 is a selective inhibitor of certain Cyclin Dependent Kinases (CDKs) leading to tumour regression.
DESCRIPTION
AT-7519 is an inhibitor of several cyclin-dependent kinases .
(GtoPdb)
DESCRIPTION
AT7519 (AT7519M) 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.
PRICE
66
DESCRIPTION
AT7519 Hydrochloride (AT7519 HCl) is a multi-CDK inhibitor for CDK1, 2, 4, 6 and 9.
(TargetMol Bioactive Compound Library)
DESCRIPTION
AT7519 is an ATP competitive CDK inhibitor with a Ki value of 38 nM for CDK1. AT7519 is inactive against all non-CDK kinases with the exception of GSK3β (IC50 = 89 nM). AT7519 shows potent antiproliferative activity in a variety of human tumor cell lines with IC50 values ranging from 40 nM for MCF-7 to 940 nM for SW620 consistent with the inhibition of CDK1 and CDK2. AT7519 induces dose-dependent cytotoxicity in multiple myeloma (MM) cell lines with IC50 values ranging from 0.5 to 2 μM at 48 hours, with the most sensitive cell lines being MM.1S (0.5 μM) and U266 (0.5 μM) and the most resistant MM.1R (>2 μM). It does not induce cytotoxicity in peripheral blood mononuclear cells (PBMNC). AT7519 partially overcomes the proliferative advantage conferred by IL6 and IGF-1 as well as the protective effect of bone marrow stromal cells (BMSCs). AT7519 induces rapid dephosphorylation of RNA pol II CTD at serine 2 and serine 5 sites, and leads to the inhibition of transcription, partially contributing to AT7519 induced cytotoxicity of MM cells. AT7519 induces activation of GSK-3β by down-regulating GSK-3β phosphorylation, which also contributes to AT7519 induced apoptosis independent of the inhibition of transcription.
A twice daily dosing of AT7519 (9.1 mg/kg) causes tumor regression of both early-stage and advanced-stage s.c. tumors in the HCT116 and HT29 colon cancer xenograft models. AT7519 treatment (15 mg/kg) inhibits tumor growth and prolongs the median overall survival of mice in the human MM xenograft mouse model in association with increased caspase 3 activation. (BOC Sciences Bioactive Compounds)
A twice daily dosing of AT7519 (9.1 mg/kg) causes tumor regression of both early-stage and advanced-stage s.c. tumors in the HCT116 and HT29 colon cancer xenograft models. AT7519 treatment (15 mg/kg) inhibits tumor growth and prolongs the median overall survival of mice in the human MM xenograft mouse model in association with increased caspase 3 activation. (BOC Sciences Bioactive Compounds)
DESCRIPTION
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 of tumor cell proliferation.
(BOC Sciences Bioactive Compounds)
DESCRIPTION
AT7519 is a CDK1/2/4/6/9 inhibitor (IC50: 10-210 nM). It is less effective to CDK3 and little active to CDK7.
(TargetMol Bioactive Compound Library)
DESCRIPTION
AT 7519 mesylate is a small-molecule inhibitor of CDK including CDK 1, 2 , 4, 5, 6, and 9 in vitro and it induces apoptosis in multiple myeloma via GSK-3β activation and RNA polymerase II inhibition.
(BOC Sciences Bioactive Compounds)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
12
Organisms
0
Compound Sets
22
Axon Medchem Screening Library
BOC Sciences Bioactive Compounds
Cayman Chemical Bioactives
CDK inhibitor database (CDKiDB)
ChEMBL Drugs
Clinical kinase drugs
Drug Repurposing Hub
DrugBank
DrugMAP
EU-OPENSCREEN Bioactive Compound Library
EUbOPEN Chemogenomics Library
Guide to Pharmacology
LSP-MoA library (Laboratory of Systems Pharmacology)
LSP-OptimalKinase library (Laboratory of Systems Pharmacology)
Novartis Chemogenetic Library (NIBR MoA Box)
ReFrame library
Selleckchem Bioactive Compound Library
Welcome Trust Cancer Drugs
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
75
Molecular Weight
381.08
Hydrogen Bond Acceptors
4
Hydrogen Bond Donors
4
Rotatable Bonds
4
Ring Count
3
Aromatic Ring Count
2
cLogP
2.45
TPSA
98.91
Fraction CSP3
0.31
Chiral centers
0.0
Largest ring
6.0
QED
0.65
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Pathway
Cell Cycle
Cell Cycle/Checkpoint
PI3K/Akt/mTOR signaling
Stem Cells
Cell Cycle/DNA Damage
Target
CDK9
Apoptosis
CDK
CDK2/CyclinA
CDK4/CyclinD1
CDK5/p35
CDK9/CyclinT
GSK-3β
GSK-3¦Â
CDK1, CDK2, CDK4, CDK5, CDK6, CDK9
Apoptosis related,CDK,GSK-3
Targets
CDK1,CDK2,CDK4,CDK5,CDK6,CDK9,CDK3
MOA
CDK inhibitor
GSK-3 inhibitor
CDK1/Cyclin B Inhibitors
Apoptosis Inducers
Inhibitors of Signal Transduction Pathways
CDK2/Cyclin A Inhibitors
Member status
member
Therapeutic Class
Anticancer Agents
Recommended Cell Concentration
None
Source data
