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cyclin dependent kinase 9

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Target not currently curated in GtoImmuPdb

Target id: 1981

Nomenclature: cyclin dependent kinase 9

Abbreviated Name: CDK9

Family: CDK9 subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 372 9q34.11 CDK9 cyclin dependent kinase 9
Mouse - 372 2 B Cdk9 cyclin-dependent kinase 9 (CDC2-related kinase)
Rat - 372 3p11 Cdk9 cyclin-dependent kinase 9
Previous and Unofficial Names Click here for help
CDC2L4 | cell division protein kinase 9 | TAK
Database Links Click here for help
Alphafold P50750 (Hs)
BRENDA 2.7.11.22, 2.7.11.23
ChEMBL Target CHEMBL3116 (Hs), CHEMBL4105875 (Mm)
Ensembl Gene ENSG00000136807 (Hs), ENSMUSG00000009555 (Mm), ENSRNOG00000022586 (Rn)
Entrez Gene 1025 (Hs), 107951 (Mm), 362110 (Rn)
Human Protein Atlas ENSG00000136807 (Hs)
KEGG Enzyme 2.7.11.22, 2.7.11.23
KEGG Gene hsa:1025 (Hs), mmu:107951 (Mm), rno:362110 (Rn)
OMIM 603251 (Hs)
Pharos P50750 (Hs)
RefSeq Nucleotide NM_001261 (Hs), NM_130860 (Mm), NM_001007743 (Rn)
RefSeq Protein NP_001252 (Hs), NP_570930 (Mm), NP_001007744 (Rn)
UniProtKB P50750 (Hs), Q99J95 (Mm), Q641Z4 (Rn)
Wikipedia CDK9 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of Human CDK9/cyclinT1
PDB Id:  3BLH
Resolution:  2.48Å
Species:  Human
References:  3
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of Human CDK9/cyclinT1 in complex with Flavopiridol
PDB Id:  3BLR
Resolution:  2.8Å
Species:  Human
References:  3
Enzyme Reaction Click here for help
EC Number: 2.7.11.22
EC Number: 2.7.11.23

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
BMS-387032 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.4 pKi 12
⤷ pKi 8.4 (Ki 4x10-9 M) [12]
seliciclib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.1 pKi 12
⤷ pKi 6.1 (Ki 7.9x10-7 M) [12]
Description: CDK9/cyclin T complex used in assay
NVP-2 Small molecule or natural product Hs Inhibition 9.3 pIC50 2
⤷ pIC50 9.3 (IC50 5x10-10 M) [2]
RGB-286638 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.0 pIC50 6
⤷ pIC50 9.0 (IC50 1x10-9 M) [6]
Description: in association with cyclin T1
zotiraciclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.5 pIC50 10
⤷ pIC50 8.5 (IC50 3x10-9 M) [10]
VIP152 Small molecule or natural product Hs Inhibition 8.5 pIC50 17
⤷ pIC50 8.5 (IC50 3x10-9 M) [17]
Description: In vitro inhibition of CDK9/CycT1 at physiological (high) ATP concentration
dinaciclib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.4 pIC50 19
⤷ pIC50 8.4 (IC50 4x10-9 M) [19]
THAL-SNS-032 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.4 pIC50 22
⤷ pIC50 8.4 (IC50 4x10-9 M) [22]
Description: Biochemical inhibition of CDK9/CycT1.
AT-7519 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition >8.0 pIC50 26
⤷ pIC50 >8.0 (IC50 <1x10-8 M) [26]
riviciclib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.7 pIC50 16
⤷ pIC50 7.7 (IC50 2x10-8 M) [16]
Description: CDK9/cyclin T1 complex
AZD5438 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.7 pIC50 5
⤷ pIC50 7.7 (IC50 2x10-8 M) [5]
Description: CDK9/cyclin T complex.
voruciclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.7 pIC50 23
⤷ pIC50 7.7 (IC50 2.2x10-8 M) [23]
Description: Inhibition of CDK9/cyclinT.
CDK inhibitor 4.35 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.6 pIC50 14
⤷ pIC50 7.6 (IC50 2.5x10-8 M) [14]
Description: Inhibition of CDK9/cyclin T1 complex.
compound 89S [PMID: 19115845] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.6 pIC50 21
⤷ pIC50 7.6 (IC50 2.8x10-8 M) [21]
Description: CDK9/cyclin T complex
kinase inhibitor 2 [PMID: 30199702] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.3 pIC50 7
⤷ pIC50 7.3 (IC50 4.9x10-8 M) [7]
Description: CDK9/cyclin T
trilaciclib Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.3 pIC50 4
⤷ pIC50 7.3 (IC50 5x10-8 M) [4]
Description: Inhibition of CDK9/cyclinT
atuveciclib Small molecule or natural product Hs Inhibition 6.4 – 7.9 pIC50 17-18
⤷ pIC50 7.9 (IC50 1.3x10-8 M) [18]
Description: Inhibition of CDK9/CycT1 in vitro, at low ATP concentration
pIC50 6.4 (IC50 3.8x10-7 M) [17]
Description: Inhibition of CDK9/CycT1 in vitro, at physiological (high) ATP concentration
BS-194 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.1 pIC50 11
⤷ pIC50 7.1 (IC50 9x10-8 M) [11]
fadraciclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.0 pIC50 25
⤷ pIC50 7.0 (IC50 1x10-7 M) [25]
Description: Inhibition of CDK9/cyclin T1
compound 18 [PMID: 20873740] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.4 pIC50 20
⤷ pIC50 6.4 (IC50 3.94x10-7 M) [20]
samuraciclib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.9 pIC50 24
⤷ pIC50 5.9 (IC50 1.2x10-6 M) [24]
Description: In a biochemical assay.
CGP74514A Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.8 pIC50 15
⤷ pIC50 5.8 (IC50 1.4x10-6 M) [15]
Description: In vitro inhibition of human CDK9/cyclin T.
SU9516 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.8 pIC50 15
⤷ pIC50 5.8 (IC50 1.5x10-6 M) [15]
Description: In vitro inhibition of CDK9/cyclin T.
milciclib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.1 pIC50 15
⤷ pIC50 5.1 (IC50 7.7x10-6 M) [15]
Description: In vitro inhibition of CDK9/cyclin T.
CDK12 inhibitor 2 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 4.8 pIC50 13
⤷ pIC50 4.8 (IC50 1.6x10-5 M) [13]
DiscoveRx KINOMEscan® screen Click here for help
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 8,27
Key to terms and symbols Click column headers to sort
Target used in screen: CDK9
Ligand Sp. Type Action Value Parameter
AT-7519 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.2 pKd
alvocidib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.2 pKd
R547 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.8 pKd
BMS-387032 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.1 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 pKd
A-674563 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.7 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 6.7 pKd
lestaurtinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 6.3 pKd
enzastaurin Small molecule or natural product Hs Inhibitor Inhibition 5.9 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.8 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen Click here for help
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx

Reference: 1,9
Key to terms and symbols Click column headers to sort
Target used in screen: CDK9-cyclin T1/CDK9-cyclin T1
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 1.4 1.0 1.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 8.5 71.0 66.0
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 15.6 0.0 -1.0
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 16.0 5.0 3.0
alsterpaullone Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 22.6 1.0 2.0
Cdk/Crk inhibitor Small molecule or natural product Hs Inhibitor Inhibition 22.7 2.0 0.0
JNK inhibitor V Small molecule or natural product Hs Inhibitor Inhibition 23.3 8.0 3.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 26.4 10.0 2.0
JNJ-7706621 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 27.6 0.0 0.0
alsterpaullone 2-cyanoethyl Small molecule or natural product Hs Inhibitor Inhibition 28.6 1.0 0.0
Target used in screen: nd/CDK9 cyclin K
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.5
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.2
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 15.8
Cdk/Crk inhibitor Small molecule or natural product Hs Inhibitor Inhibition 21.6
alsterpaullone 2-cyanoethyl Small molecule or natural product Hs Inhibitor Inhibition 23.7
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 23.8
alsterpaullone Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 24.2
K-252a Small molecule or natural product Hs Inhibitor Inhibition 25.4
JNK inhibitor V Small molecule or natural product Hs Inhibitor Inhibition 26.6
JNJ-7706621 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 27.4
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes
GO:0071345 cellular response to cytokine stimulus IDA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes
GO:2001168 positive regulation of histone H2B ubiquitination IMP

References

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1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]

2. Barsanti PA et al.. (2011) Pyridine and pyrazine derivatives as protein kinase modulators. Patent number: WO2011012661. Assignee: Novartis Ag. Priority date: 30/07/2009. Publication date: 03/02/2011.

3. Baumli S, Lolli G, Lowe ED, Troiani S, Rusconi L, Bullock AN, Debreczeni JE, Knapp S, Johnson LN. (2008) The structure of P-TEFb (CDK9/cyclin T1), its complex with flavopiridol and regulation by phosphorylation. EMBO J, 27 (13): 1907-18. [PMID:18566585]

4. Bisi JE, Sorrentino JA, Roberts PJ, Tavares FX, Strum JC. (2016) Preclinical Characterization of G1T28: A Novel CDK4/6 Inhibitor for Reduction of Chemotherapy-Induced Myelosuppression. Mol Cancer Ther, 15 (5): 783-93. [PMID:26826116]

5. Byth KF, Thomas A, Hughes G, Forder C, McGregor A, Geh C, Oakes S, Green C, Walker M, Newcombe N et al.. (2009) AZD5438, a potent oral inhibitor of cyclin-dependent kinases 1, 2, and 9, leads to pharmacodynamic changes and potent antitumor effects in human tumor xenografts. Mol Cancer Ther, 8 (7): 1856-66. [PMID:19509270]

6. Cirstea D, Hideshima T, Santo L, Eda H, Mishima Y, Nemani N, Hu Y, Mimura N, Cottini F, Gorgun G et al.. (2013) Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs. Leukemia, 27 (12): 2366-75. [PMID:23807770]

7. Compain G, Oumata N, Clarhaut J, Péraudeau E, Renoux B, Galons H, Papot S. (2018) A β-glucuronidase-responsive albumin-binding prodrug for potential selective kinase inhibitor-based cancer chemotherapy. Eur J Med Chem, 158: 1-6. [PMID:30199702]

8. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]

9. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem J, 451 (2): 313-28. [PMID:23398362]

10. Goh KC, Novotny-Diermayr V, Hart S, Ong LC, Loh YK, Cheong A, Tan YC, Hu C, Jayaraman R, William AD et al.. (2012) TG02, a novel oral multi-kinase inhibitor of CDKs, JAK2 and FLT3 with potent anti-leukemic properties. Leukemia, 26 (2): 236-43. [PMID:21860433]

11. Heathcote DA, Patel H, Kroll SH, Hazel P, Periyasamy M, Alikian M, Kanneganti SK, Jogalekar AS, Scheiper B, Barbazanges M et al.. (2010) A novel pyrazolo[1,5-a]pyrimidine is a potent inhibitor of cyclin-dependent protein kinases 1, 2, and 9, which demonstrates antitumor effects in human tumor xenografts following oral administration. J Med Chem, 53 (24): 8508-22. [PMID:21080703]

12. Hole AJ, Baumli S, Shao H, Shi S, Huang S, Pepper C, Fischer PM, Wang S, Endicott JA, Noble ME. (2013) Comparative structural and functional studies of 4-(thiazol-5-yl)-2-(phenylamino)pyrimidine-5-carbonitrile CDK9 inhibitors suggest the basis for isotype selectivity. J Med Chem, 56 (3): 660-70. [PMID:23252711]

13. Ito M, Tanaka T, Toita A, Uchiyama N, Kokubo H, Morishita N, Klein MG, Zou H, Murakami M, Kondo M et al.. (2018) Discovery of 3-Benzyl-1-( trans-4-((5-cyanopyridin-2-yl)amino)cyclohexyl)-1-arylurea Derivatives as Novel and Selective Cyclin-Dependent Kinase 12 (CDK12) Inhibitors. J Med Chem, 61 (17): 7710-7728. [PMID:30067358]

14. Jorda R, Havlíček L, Šturc A, Tušková D, Daumová L, Alam M, Škerlová J, Nekardová M, Peřina M, Pospíšil T et al.. (2019) 3,5,7-Substituted Pyrazolo[4,3- d]pyrimidine Inhibitors of Cyclin-Dependent Kinases and Their Evaluation in Lymphoma Models. J Med Chem, 62 (9): 4606-4623. DOI: 10.1021/acs.jmedchem.9b00189 [PMID:30943029]

15. Jorda R, Hendrychová D, Voller J, Řezníčková E, Gucký T, Kryštof V. (2018) How Selective Are Pharmacological Inhibitors of Cell-Cycle-Regulating Cyclin-Dependent Kinases?. J Med Chem, 61 (20): 9105-9120. [PMID:30234987]

16. Joshi KS, Rathos MJ, Joshi RD, Sivakumar M, Mascarenhas M, Kamble S, Lal B, Sharma S. (2007) In vitro antitumor properties of a novel cyclin-dependent kinase inhibitor, P276-00. Mol Cancer Ther, 6 (3): 918-25. [PMID:17363486]

17. Lücking U, Kosemund D, Böhnke N, Lienau P, Siemeister G, Denner K, Bohlmann R, Briem H, Terebesi I, Bömer U et al.. (2021) Changing for the Better: Discovery of the Highly Potent and Selective CDK9 Inhibitor VIP152 Suitable for Once Weekly Intravenous Dosing for the Treatment of Cancer. J Med Chem, 64 (15): 11651-11674. [PMID:34264057]

18. Lücking U, Scholz A, Lienau P, Siemeister G, Kosemund D, Bohlmann R, Briem H, Terebesi I, Meyer K, Prelle K et al.. (2017) Identification of Atuveciclib (BAY 1143572), the First Highly Selective, Clinical PTEFb/CDK9 Inhibitor for the Treatment of Cancer. ChemMedChem, 12 (21): 1776-1793. [PMID:28961375]

19. Martin MP, Olesen SH, Georg GI, Schönbrunn E. (2013) Cyclin-dependent kinase inhibitor dinaciclib interacts with the acetyl-lysine recognition site of bromodomains. ACS Chem Biol, 8 (11): 2360-5. [PMID:24007471]

20. Menichincheri M, Albanese C, Alli C, Ballinari D, Bargiotti A, Caldarelli M, Ciavolella A, Cirla A, Colombo M, Colotta F et al.. (2010) Cdc7 kinase inhibitors: 5-heteroaryl-3-carboxamido-2-aryl pyrroles as potential antitumor agents. 1. Lead finding. J Med Chem, 53 (20): 7296-315. [PMID:20873740]

21. Menichincheri M, Bargiotti A, Berthelsen J, Bertrand JA, Bossi R, Ciavolella A, Cirla A, Cristiani C, Croci V, D'Alessio R et al.. (2009) First Cdc7 kinase inhibitors: pyrrolopyridinones as potent and orally active antitumor agents. 2. Lead discovery. J Med Chem, 52 (2): 293-307. [PMID:19115845]

22. Olson CM, Jiang B, Erb MA, Liang Y, Doctor ZM, Zhang Z, Zhang T, Kwiatkowski N, Boukhali M, Green JL et al.. (2018) Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation. Nat Chem Biol, 14 (2): 163-170. [PMID:29251720]

23. Paiva C, Godbersen JC, Soderquist RS, Rowland T, Kilmarx S, Spurgeon SE, Brown JR, Srinivasa SP, Danilov AV. (2015) Cyclin-Dependent Kinase Inhibitor P1446A Induces Apoptosis in a JNK/p38 MAPK-Dependent Manner in Chronic Lymphocytic Leukemia B-Cells. PLoS ONE, 10 (11): e0143685. [PMID:26606677]

24. Patel H, Periyasamy M, Sava GP, Bondke A, Slafer BW, Kroll SHB, Barbazanges M, Starkey R, Ottaviani S, Harrod A et al.. (2018) ICEC0942, an Orally Bioavailable Selective Inhibitor of CDK7 for Cancer Treatment. Mol Cancer Ther, 17 (6): 1156-1166. [PMID:29545334]

25. Sheldrake PW, Atrash B, Green S, Mcdonald E, Frame S. (2008) 2, 6, 9-substituted purine derivatives having anti proliferative properties. Patent number: WO2008122767A2. Assignee: Cyclacel Limited, Cancer Research Technology Limited. Priority date: 04/04/2007. Publication date: 16/10/2008.

26. Squires MS, Feltell RE, Wallis NG, Lewis EJ, Smith DM, Cross DM, Lyons JF, Thompson NT. (2009) Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines. Mol Cancer Ther, 8 (2): 324-32. [PMID:19174555]

27. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem Biol, 17 (11): 1241-9. [PMID:21095574]

How to cite this page

CDK9 subfamily: cyclin dependent kinase 9. Last modified on 17/08/2021. Accessed on 17/10/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1981.