Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMQF982)

• Drug Name: AEW-541 Drug Info
• Synonyms: AECDBHGVIIRMOI-UHFFFAOYSA-N; NVP-AEW541; 475489-16-8; 475488-34-7; AEW541; NVP-AEW 541; UNII-97QB5037VR; AEW 541; AVP-AEW541; 7-((1s,3s)-3-(azetidin-1-ylmethyl)cyclobutyl)-5-(3-(benzyloxy)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine; CHEMBL1614712; 97QB5037VR; 7-[TRANS-3-(1-AZETIDINYLMETHYL)CYCLOBUTYL]-5-[3-(PHENYLMETHOXY)PHENYL]-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE; C27H29N5O; 7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE, 7-[CIS-3-(1-AZETIDINYLMETHYL)CYCLOBUTYL]-5-[3-(PHENYLMETHOXY)PHENYL]-

Indication

Disease Entry	ICD 11	Status	REF
Multiple myeloma	2A83	Phase 1	[1]

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  PubChem CID: 11476171
  CAS Number: CAS 475488-34-7
  TTD Drug ID: DMQF982

Molecule-Related Drug Atlas

Drug(s) Targeting Insulin-like growth factor I receptor (IGF1R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Teprotumumab	DM4L59B	Graves disease	5A02.0	Approved	[6]
Mecasermin	DM1O3BY	Growth failure	LD2F.1Y	Approved	[7]
Somatomedin-1	DMZ9FAO	Hormone deficiency	5A61.1	Approved	[8]
OSI-906	DMHKZLF	Solid tumour/cancer	2A00-2F9Z	Phase 3	[9]
Rinfabate	DML9FD4	Solid tumour/cancer	2A00-2F9Z	Phase 2/3	[10]
MM-141	DM2RJ4D	Pancreatic cancer	2C10	Phase 2	[11]
TT-100	DMZE6Y9	Non-small-cell lung cancer	2C25.Y	Phase 2	[12]
AMG 479	DM0DRAZ	Breast cancer	2C60-2C65	Phase 2	[13]
VPI-2690B	DMUQZT4	Diabetic nephropathy	GB61.Z	Phase 2	[14]
AXL-1717	DMTQ1Y3	Solid tumour/cancer	2A00-2F9Z	Phase 2	[15]

Drug(s) Targeting Insulin receptor (INSR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Meglitinides	DM1OFHN	Type-2 diabetes	5A11	Approved	[16]
Human neutral insulin	DMA5OBU	Diabetic complication	5A2Y	Approved	[17]
Insulin Lyspro recombinant	DM5XHVR	Diabetic complication	5A2Y	Approved	[17]
Insulin, porcine	DMO95XI	Diabetic complication	5A2Y	Approved	[18]
Insulin recombinant	DMYVP5G	Diabetic complication	5A2Y	Approved	[17]
Metformin arginine-hemisuccinimide	DMTPAM3	Type-2 diabetes	5A11	Approved	[19]
Insulin-lispro	DM4O90W	Diabetic complication	5A2Y	Approved	[20]
Insulin-glulisine	DMQI0FU	Diabetic complication	5A2Y	Approved	[21]
Ryzodeq	DMOFP18	Type-2 diabetes	5A11	Approved	[22]
NN5401	DM0QV27	Diabetic complication	5A2Y	Phase 3	[22]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Insulin receptor (INSR)	TTCBFJO	INSR_HUMAN	Inhibitor	[2]
Insulin-like growth factor I receptor (IGF1R)	TTHRID2	IGF1R_HUMAN	Inhibitor	[3] , [4] , [5]

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 800019974)
• [2] Inhibition of the insulin-like growth factor-1 receptor (IGF1R) tyrosine kinase as a novel cancer therapy approach. J Med Chem. 2009 Aug 27;52(16):4981-5004.
• [3] 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.
• [4] Co-targeting the EGFR and IGF-IR with anti-EGFR monoclonal antibody ICR62 and the IGF-IR tyrosine kinase inhibitor NVP-AEW541 in colorectal cancer cells. Int J Oncol. 2008 Nov;33(5):1107-13.
• [5] FAK and IGF-IR interact to provide survival signals in human pancreatic adenocarcinoma cells. Carcinogenesis. 2008 Jun;29(6):1096-107.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [7] 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.
• [8] 2005 approvals: Safety first. Nature Reviews Drug Discovery 5, 92-93 (February 2006).
• [9] 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.
• [10] 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.
• [11] 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.
• [12] BiPar Sciences Co-founder Reunites Management Team At TriAct Therapeutics to Advance Clinical Stage Cancer Programs. TriAct Therapeutics. Sept. 10, 2009.
• [13] Clinical pipeline report, company report or official report of Amgen (2009).
• [14] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [15] 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.
• [16] New drugs for type 2 diabetes mellitus: what is their place in therapy Drugs. 2008;68(15):2131-62.
• [17] Knockouts model the 100 best-selling drugs--will they model the next 100 Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
• [18] 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.
• [19] Metformin (Glucophage) inhibits tyrosine phosphatase activity to stimulate the insulin receptor tyrosine kinase. Biochem Pharmacol. 2004 Jun 1;67(11):2081-91.
• [20] Hope for insulin mimetic oral antidiabetic drugs. Eur J Endocrinol. 1999 Dec;141(6):561-2.
• [21] Insulin glulisine: a review of its use in the management of diabetes mellitus. Drugs. 2009;69(8):1035-57.
• [22] 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).