General Information of Drug (ID: DMAGVXW)

Drug Name
KENPAULLONE
Synonyms
kenpaullone; 142273-20-9; 9-Bromopaullone; NSC 664704; 9-Bromo-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one; NSC-664704; NSC664704; MLS002702152; CHEMBL296586; 9-Bromo-7,12-dihydroindolo(3,2-d)(1)benzazepin-6(5H)-one; Indolo[3,2-d][1]benzazepin-6(5H)-one,9-bromo-7,12-dihydro-; QQUXFYAWXPMDOE-UHFFFAOYSA-N; 9-Bromo-7,12-dihydro-indolo[3,2-d][1]benzazepin-6(5H)-one; 9-bromo-7,12-dihydro-5H-indolo[3,2-d][1]benzazepin-6-one; 9-Bromo-7,12-dihydro-indolo-[3,2-d]-[1]benzazepin-6(5H)-one
Indication
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 327.17
Topological Polar Surface Area (xlogp) 3.3
Rotatable Bond Count (rotbonds) 0
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 1
Chemical Identifiers
Formula
C16H11BrN2O
IUPAC Name
9-bromo-7,12-dihydro-5H-indolo[3,2-d][1]benzazepin-6-one
Canonical SMILES
C1C2=C(C3=CC=CC=C3NC1=O)NC4=C2C=C(C=C4)Br
InChI
InChI=1S/C16H11BrN2O/c17-9-5-6-14-11(7-9)12-8-15(20)18-13-4-2-1-3-10(13)16(12)19-14/h1-7,19H,8H2,(H,18,20)
InChIKey
QQUXFYAWXPMDOE-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
3820
ChEBI ID
CHEBI:92658
CAS Number
142273-20-9
TTD ID
D00PWQ

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Cyclin-dependent kinase 1 (CDK1) TTH6V3D CDK1_HUMAN Inhibitor [2]
Cyclin-dependent kinase 5 (CDK5) TTL4Q97 CDK5_HUMAN Inhibitor [3]
G2/mitotic-specific cyclin B1 (CCNB1) TT9P6OW CCNB1_HUMAN Inhibitor [2]
Glycogen synthase kinase-3 alpha (GSK-3A) TTRZQE3 GSK3A_HUMAN Inhibitor [4]
Glycogen synthase kinase-3 beta (GSK-3B) TTRSMW9 GSK3B_HUMAN Inhibitor [3]
Plasmodium CDK Pfmrk (Malaria Pfmrk) TTSFWA7 P90584_PLAFA Inhibitor [5]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6000).
2 Discovery of novel CDK1 inhibitors by combining pharmacophore modeling, QSAR analysis and in silico screening followed by in vitro bioassay. Eur J Med Chem. 2010 Sep;45(9):4316-30.
3 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta. Bioorg Med Chem Lett. 2004 Jan 19;14(2):413-6.
4 Glycogen synthase kinase 3 (GSK-3) inhibitors: a patent update (2014-2015).Expert Opin Ther Pat. 2017 Jun;27(6):657-666.
5 A three-dimensional in silico pharmacophore model for inhibition of Plasmodium falciparum cyclin-dependent kinases and discovery of different class... J Med Chem. 2004 Oct 21;47(22):5418-26.
6 Activity of substituted thiophene sulfonamides against malarial and mammalian cyclin dependent protein kinases, Bioorg. Med. Chem. Lett. 20(13):3863-3867 (2010).
7 Selective inhibition of Pfmrk, a Plasmodium falciparum CDK, by antimalarial 1,3-diaryl-2-propenones. Bioorg Med Chem Lett. 2009 Apr 1;19(7):1982-5.
8 Novel molecular targets for antimalarial chemotherapy. Int J Antimicrob Agents. 2007 Jul;30(1):4-10.
9 Evaluation of broad spectrum protein kinase inhibitors to probe the architecture of the malarial cyclin dependent protein kinase Pfmrk. Bioorg Med Chem Lett. 2007 Sep 1;17(17):4961-6.
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11 Pharmacological inhibitors of cyclin-dependent kinases. Trends Pharmacol Sci. 2002 Sep;23(9):417-25.
12 Aloisines, a new family of CDK/GSK-3 inhibitors. SAR study, crystal structure in complex with CDK2, enzyme selectivity, and cellular effects. J Med Chem. 2003 Jan 16;46(2):222-36.
13 Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
14 A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
15 P276-00, a novel cyclin-dependent inhibitor induces G1-G2 arrest, shows antitumor activity on cisplatin-resistant cells and significant in vivo efficacy in tumor models. Mol Cancer Ther. 2007 Mar;6(3):926-34.
16 Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs. Leukemia. 2013 Dec;27(12):2366-75.
17 A first in man, phase I dose-escalation study of PHA-793887, an inhibitor of multiple cyclin-dependent kinases (CDK2, 1 and 4) reveals unexpected h... Cell Cycle. 2011 Mar 15;10(6):963-70.
18 c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.
19 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
20 The GSK3 kinase inhibitor lithium produces unexpected hyperphosphorylation of -catenin, a GSK3 substrate, in human glioblastoma cells. Biol Open. 2018 Jan 26;7(1):bio030874.
21 Evidence for irreversible inhibition of glycogen synthase kinase-3beta by tideglusib. J Biol Chem. 2012 Jan 6;287(2):893-904.
22 9-ING-41, a small molecule inhibitor of GSK-3beta, potentiates the effects of anticancer therapeutics in bladder cancer. Sci Rep. 2019 Dec 27;9(1):19977.
23 Company report (Neurim Pharmaceuticals)
24 Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo. Diabetes. 2003 Mar;52(3):588-95.
25 Identification of novel scaffold of benzothiazepinones as non-ATP competitive glycogen synthase kinase-3beta inhibitors through virtual screening. Bioorg Med Chem Lett. 2012 Dec 1;22(23):7232-6.
26 Fragment and knowledge-based design of selective GSK-3beta inhibitors using virtual screening models. Eur J Med Chem. 2009 Jun;44(6):2361-71.
27 Challenges and new opportunities in the investigation of new drug therapies to treat frontotemporal dementia. Expert Opin Ther Targets. 2008 Nov;12(11):1367-76.
28 Design of new inhibitors for cdc2 kinase based on a multiple pseudosubstrate structure. Bioorg Med Chem Lett. 1998 May 5;8(9):1019-22.
29 Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors. J Med Chem. 2006 Feb 23;49(4):1271-81.
30 Synthesis and cytotoxic activity of 2-methylimidazo[1,2-a]pyridine- and quinoline-substituted 2-aminopyrimidine derivatives. Eur J Med Chem. 2010 Jan;45(1):379-86.