Details of the Drug

General Information of Drug (ID: DMYLVQF)

• Drug Name: indirubin deriv. 8a

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 398.2
  Topological Polar Surface Area (xlogp); 3.8
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 5
• Chemical Identifiers:
  Formula: C18H12BrN3O3
  IUPAC Name: [(E)-[2-(6-bromo-2-hydroxy-1H-indol-3-yl)indol-3-ylidene]amino] acetate
  Canonical SMILES: CC(=O)O/N=C/1\\C2=CC=CC=C2N=C1C3=C(NC4=C3C=CC(=C4)Br)O
  InChI: InChI=1S/C18H12BrN3O3/c1-9(23)25-22-16-12-4-2-3-5-13(12)20-17(16)15-11-7-6-10(19)8-14(11)21-18(15)24/h2-8,21,24H,1H3/b22-16+
  InChIKey: HUDSYNWJCPDHLL-CJLVFECKSA-N
• Cross-matching ID:
  PubChem CID: 135398521
  CAS Number: 667463-85-6
  TTD ID: D0B3ZB

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Glycogen synthase kinase-3 beta (GSK-3B)	TTRSMW9	GSK3B_HUMAN	Inhibitor	[1]
GSK3A messenger RNA (GSK3A mRNA)	TTQWAU1	GSK3A_HUMAN	Inhibitor	[1]

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

References

• [1] Structural basis for the synthesis of indirubins as potent and selective inhibitors of glycogen synthase kinase-3 and cyclin-dependent kinases. J Med Chem. 2004 Feb 12;47(4):935-46.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Glycogen synthase kinase 3 (GSK-3) inhibitors: a patent update (2014-2015).Expert Opin Ther Pat. 2017 Jun;27(6):657-666.
• [4] 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.
• [5] Evidence for irreversible inhibition of glycogen synthase kinase-3beta by tideglusib. J Biol Chem. 2012 Jan 6;287(2):893-904.
• [6] 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.
• [7] Company report (Neurim Pharmaceuticals)
• [8] 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta. Bioorg Med Chem Lett. 2004 Jan 19;14(2):413-6.
• [9] 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.
• [10] 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.
• [11] Fragment and knowledge-based design of selective GSK-3beta inhibitors using virtual screening models. Eur J Med Chem. 2009 Jun;44(6):2361-71.
• [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] Synthesis and preliminary biological evaluation of new derivatives of the marine alkaloid leucettamine B as kinase inhibitors. Eur J Med Chem. 2010 Feb;45(2):805-10.
• [14] US patent application no. 6,316,259, Antisense inhibition of glycogen synthase kinase 3 alpha expression.