Details of the Drug

General Information of Drug (ID: DM7QGSX)

• Drug Name: KW-2450

Indication

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Discontinued in Phase 1/2	[1]

• #Ro5 Violations (Lipinski): 1:
  Molecular Weight; 687.8
  Topological Polar Surface Area; Not Available
  Rotatable Bond Count; 8
  Hydrogen Bond Donor Count; 4
  Hydrogen Bond Acceptor Count; 9
• Chemical Identifiers:
  Formula: C35H37N5O6S2
  IUPAC Name: N-[5-[[4-(2-hydroxyacetyl)piperazin-1-yl]methyl]-2-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-3-methylthiophene-2-carboxamide;4-methylbenzenesulfonic acid
  Canonical SMILES: CC1=CC=C(C=C1)S(=O)(=O)O.CC1=C(SC=C1)C(=O)NC2=C(C=CC(=C2)CN3CCN(CC3)C(=O)CO)/C=C/C4=NNC5=CC=CC=C54
  InChI: InChI=1S/C28H29N5O3S.C7H8O3S/c1-19-10-15-37-27(19)28(36)29-25-16-20(17-32-11-13-33(14-12-32)26(35)18-34)6-7-21(25)8-9-24-22-4-2-3-5-23(22)30-31-24;1-6-2-4-7(5-3-6)11(8,9)10/h2-10,15-16,34H,11-14,17-18H2,1H3,(H,29,36)(H,30,31);2-5H,1H3,(H,8,9,10)/b9-8+
  InChIKey: SIJKXSMUXNJNQM-HRNDJLQDSA-N
• Cross-matching ID:
  PubChem CID: 56847547
  CAS Number: 1360433-93-7
  TTD ID: D0M3OR

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Insulin receptor (INSR)	TTCBFJO	INSR_HUMAN	Modulator	[2]
Insulin-like growth factor I receptor (IGF1R)	TTHRID2	IGF1R_HUMAN	Modulator	[2]

Molecular Expression Atlas of This Drug

• The Studied Disease: Breast cancer
• ICD Disease Classification: 2C60-2C65

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Insulin receptor (INSR)	DTT	INSR	1.03E-05	0.26	0.66

References

• [1] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800030562)
• [2] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [4] 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.
• [5] 2005 approvals: Safety first. Nature Reviews Drug Discovery 5, 92-93 (February 2006).
• [6] 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.
• [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] New drugs for type 2 diabetes mellitus: what is their place in therapy Drugs. 2008;68(15):2131-62.
• [14] Knockouts model the 100 best-selling drugs--will they model the next 100 Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
• [15] Acidic residues on the N-terminus of proinsulin C-Peptide are important for the folding of insulin precursor. J Biochem. 2002 Jun;131(6):855-9.
• [16] Metformin (Glucophage) inhibits tyrosine phosphatase activity to stimulate the insulin receptor tyrosine kinase. Biochem Pharmacol. 2004 Jun 1;67(11):2081-91.
• [17] Hope for insulin mimetic oral antidiabetic drugs. Eur J Endocrinol. 1999 Dec;141(6):561-2.
• [18] Insulin glulisine: a review of its use in the management of diabetes mellitus. Drugs. 2009;69(8):1035-57.
• [19] 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. (Target id: 1800).