Details of the Drug

General Information of Drug (ID: DM57TY3)

• Drug Name: 9-ING-41
• Synonyms: 1034895-42-5; ND1SOF0DLU; UNII-ND1SOF0DLU; CHEMBL483465; 3-(5-fluoro-1-benzofuran-3-yl)-4-(5-methyl-[1,3]dioxolo[4,5-f]indol-7-yl)pyrrole-2,5-dione; 3-(5-fluorobenzofuran-3-yl)-4-(5-methyl-5H-[1,3]dioxolo[4,5-f]indol-7-yl)-1H-pyrrole-2,5-dione; elraglusib; SCHEMBL3152351; GTPL11412; EX-A4074; BDBM50267716; s9602; SB19735; compound 26 [PMID: 19338355]; HY-113914; CS-0063319; 1H-Pyrrole-2,5-dione, 3-(5-fluoro-3-benzofuranyl)-4-(5-methyl-5H-1,3-dioxolo(4,5-F)indol-7-yl)-; 3-(5-Fluoro-benzofuran-3-yl)-4-(5-methyl-5H-(1,3)dioxolo(4,5-F)indol-7-yl)-pyrrole-2,5-dione; 3-(5-Fluorobenzofuran-3-yl)-4-(5-methyl-5H-[1,3]dioxolo[4,5-f]indol-7-yl)pyrrole-2,5-dione; 4-(5-methyl-5H-[1,3]dioxolo[4,5-f]-indol-7-yl)-3-(5-fluoro-1-benzofuran-3-yl)-1 h-pyrrole-2,5-dione

Indication

Disease Entry	ICD 11	Status	REF
Myelofibrosis	2A20.2	Phase 2	[1]
Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 404.3
  Topological Polar Surface Area (xlogp); 3
  Rotatable Bond Count (rotbonds); 2
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 6
• Chemical Identifiers:
  Formula: C22H13FN2O5
  IUPAC Name: 3-(5-fluoro-1-benzofuran-3-yl)-4-(5-methyl-[1,3]dioxolo[4,5-f]indol-7-yl)pyrrole-2,5-dione
  Canonical SMILES: CN1C=C(C2=CC3=C(C=C21)OCO3)C4=C(C(=O)NC4=O)C5=COC6=C5C=C(C=C6)F
  InChI: InChI=1S/C22H13FN2O5/c1-25-7-13(11-5-17-18(6-15(11)25)30-9-29-17)19-20(22(27)24-21(19)26)14-8-28-16-3-2-10(23)4-12(14)16/h2-8H,9H2,1H3,(H,24,26,27)
  InChIKey: FARXPFGGGGLENU-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 44582816
  CAS Number: 1034895-42-5
  DrugBank ID: DB16047
  TTD ID: D4USX5

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	[3]

Molecular Expression Atlas of This Drug

• The Studied Disease: Myelofibrosis
• ICD Disease Classification: 2A20.2

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] ClinicalTrials.gov (NCT04218071) Actuate 1901: 9-ING-41 in Myelofibrosis. U.S. National Institutes of Health.
• [2] ClinicalTrials.gov (NCT04239092) 9-ING-41 in Pediatric Patients With Refractory Malignancies.. U.S. National Institutes of Health.
• [3] 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.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] Glycogen synthase kinase 3 (GSK-3) inhibitors: a patent update (2014-2015).Expert Opin Ther Pat. 2017 Jun;27(6):657-666.
• [6] 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.
• [7] Evidence for irreversible inhibition of glycogen synthase kinase-3beta by tideglusib. J Biol Chem. 2012 Jan 6;287(2):893-904.
• [8] Company report (Neurim Pharmaceuticals)
• [9] 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta. Bioorg Med Chem Lett. 2004 Jan 19;14(2):413-6.
• [10] 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.
• [11] 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.
• [12] Fragment and knowledge-based design of selective GSK-3beta inhibitors using virtual screening models. Eur J Med Chem. 2009 Jun;44(6):2361-71.
• [13] Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.