Details of the Drug

General Information of Drug (ID: DMIOTHG)

Drug Name
Thieno analogue of kenpaullone
Synonyms
Thieno analogue of kenpaullone; Paullone Analogue 71; CHEMBL323657; SCHEMBL5688610; BDBM7336; NSC 703058; 8-Bromo-6,11-dihydro-thieno[3 ,2 :2,3]azepino[4,5-b]indol-5(4H)-one; 9-Bromo-5,4-(epithioetheno)-1,2,3,6-tetrahydroazepino[4,5-b]indole-2-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) 333.2
Topological Polar Surface Area (xlogp) 3
Rotatable Bond Count (rotbonds) 0
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 2
Chemical Identifiers
Formula
C14H9BrN2OS
IUPAC Name
13-bromo-3-thia-7,17-diazatetracyclo[8.7.0.02,6.011,16]heptadeca-1(10),2(6),4,11(16),12,14-hexaen-8-one
Canonical SMILES
C1C2=C(C3=C(C=CS3)NC1=O)NC4=C2C=C(C=C4)Br
InChI
InChI=1S/C14H9BrN2OS/c15-7-1-2-10-8(5-7)9-6-12(18)16-11-3-4-19-14(11)13(9)17-10/h1-5,17H,6H2,(H,16,18)
InChIKey
XLKHCIUFNPNLIE-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
6538761
TTD ID
D0TF9P

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 [1]
Cyclin-dependent kinase 5 (CDK5) TTL4Q97 CDK5_HUMAN Inhibitor [1]
G2/mitotic-specific cyclin B1 (CCNB1) TT9P6OW CCNB1_HUMAN Inhibitor [1]
Glycogen synthase kinase-3 beta (GSK-3B) TTRSMW9 GSK3B_HUMAN Inhibitor [1]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Discovery agent
ICD Disease Classification N.A.
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Glycogen synthase kinase-3 beta (GSK-3B) DTT GSK3B 1.26E-01 -0.23 -0.77
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta. Bioorg Med Chem Lett. 2004 Jan 19;14(2):413-6.
2 Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.
3 Pharmacological inhibitors of cyclin-dependent kinases. Trends Pharmacol Sci. 2002 Sep;23(9):417-25.
4 Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
5 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.
6 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.
7 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.
8 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.
9 c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.
10 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.
11 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
12 Glycogen synthase kinase 3 (GSK-3) inhibitors: a patent update (2014-2015).Expert Opin Ther Pat. 2017 Jun;27(6):657-666.
13 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.
14 Evidence for irreversible inhibition of glycogen synthase kinase-3beta by tideglusib. J Biol Chem. 2012 Jan 6;287(2):893-904.
15 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.
16 Company report (Neurim Pharmaceuticals)
17 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.
18 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.
19 Fragment and knowledge-based design of selective GSK-3beta inhibitors using virtual screening models. Eur J Med Chem. 2009 Jun;44(6):2361-71.
20 Design of new inhibitors for cdc2 kinase based on a multiple pseudosubstrate structure. Bioorg Med Chem Lett. 1998 May 5;8(9):1019-22.
21 Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors. J Med Chem. 2006 Feb 23;49(4):1271-81.
22 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.