Details of the Drug

General Information of Drug (ID: DMHKZLF)

• Drug Name: OSI-906
• Synonyms: Linsitinib; 867160-71-2; OSI-906; Linsitinib(OSI-906); OSI906; OSI 906; OSI-906AA; OSI-906 (Linsitinib); UNII-15A52GPT8T; Kinome_3532; ASP-7487; 3-[8-amino-1-(2-phenylquinolin-7-yl)imidazo[1,5-a]pyrazin-3-yl]-1-methylcyclobutan-1-ol; 15A52GPT8T; CHEMBL1091644; MMV676605; cis-3-[8-Amino-1-(2-phenyl-7-quinolinyl)imidazo[1,5-a]pyrazin-3-yl]-1-methylcyclobutanol; C26H23N5O; cis-3-(8-amino-1-(2-phenyl-7-quinolinyl)imidazo(1,5-a)pyrazin-3-yl)-1-methylcyclobutanol; Linsitinib [USAN:INN]; OSI906/Linsitinib/; Linsitinib; OSI-906

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 3	[1], [2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 421.5
  Topological Polar Surface Area (xlogp); 4.2
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 5
• Chemical Identifiers:
  Formula: C26H23N5O
  IUPAC Name: 3-[8-amino-1-(2-phenylquinolin-7-yl)imidazo[1,5-a]pyrazin-3-yl]-1-methylcyclobutan-1-ol
  Canonical SMILES: CC1(CC(C1)C2=NC(=C3N2C=CN=C3N)C4=CC5=C(C=C4)C=CC(=N5)C6=CC=CC=C6)O
  InChI: InChI=1S/C26H23N5O/c1-26(32)14-19(15-26)25-30-22(23-24(27)28-11-12-31(23)25)18-8-7-17-9-10-20(29-21(17)13-18)16-5-3-2-4-6-16/h2-13,19,32H,14-15H2,1H3,(H2,27,28)
  InChIKey: PKCDDUHJAFVJJB-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 11640390
  ChEBI ID: CHEBI:91402
  CAS Number: 867160-71-2
  TTD ID: D01GFX

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Insulin-like growth factor I receptor (IGF1R)	TTHRID2	IGF1R_HUMAN	Inhibitor	[3]

Molecular Expression Atlas of This Drug

• The Studied Disease: Solid tumour/cancer
• ICD Disease Classification: 2A00-2F9Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Insulin-like growth factor I receptor (IGF1R)	DTT	IGF1R	1.64E-01	0.25	0.64

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: 7423).
• [2] ClinicalTrials.gov (NCT00924989) A Study of OSI-906 in Patients With Locally Advanced or Metastatic Adrenocortical Carcinoma. U.S. National Institutes of Health.
• [3] Imidazo[2,1-b]thiazoles: multitargeted inhibitors of both the insulin-like growth factor receptor and members of the epidermal growth factor family... Bioorg Med Chem Lett. 2010 Apr 15;20(8):2452-5.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [5] IGF-1R, IGF-1 and IGF-2 expression as potential prognostic and predictive markers in colorectal-cancer. Virchows Arch. 2003 Aug;443(2):139-45.
• [6] 2005 approvals: Safety first. Nature Reviews Drug Discovery 5, 92-93 (February 2006).
• [7] Mecasermin rinfabate: insulin-like growth factor-I/insulin-like growth factor binding protein-3, mecaserimin rinfibate, rhIGF-I/rhIGFBP-3. Drugs R D. 2005;6(2):120-7.
• [8] MM-141, an IGF-IR- and ErbB3-directed bispecific antibody, overcomes network adaptations that limit activity of IGF-IR inhibitors. Mol Cancer Ther. 2014 Feb;13(2):410-25.
• [9] BiPar Sciences Co-founder Reunites Management Team At TriAct Therapeutics to Advance Clinical Stage Cancer Programs. TriAct Therapeutics. Sept. 10, 2009.
• [10] Clinical pipeline report, company report or official report of Amgen (2009).
• [11] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [12] Clinical Phase I study with an Insulin-like Growth Factor-1 receptor inhibitor: experiences in patients with squamous non-small cell lung carcinoma. Acta Oncol. 2011 Apr;50(3):441-7.
• [13] Clinical pipeline report, company report or official report of Roche (2009).