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

Molecule Type:

DTT

DOT

Drug Status:

Approved Drug(s)

Clinical Trial Drug(s)

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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	[5]
Mecasermin	DM1O3BY	Growth failure	LD2F.1Y	Approved	[6]
Somatomedin-1	DMZ9FAO	Hormone deficiency	5A61.1	Approved	[7]
OSI-906	DMHKZLF	Solid tumour/cancer	2A00-2F9Z	Phase 3	[8]
Rinfabate	DML9FD4	Solid tumour/cancer	2A00-2F9Z	Phase 2/3	[9]
MM-141	DM2RJ4D	Pancreatic cancer	2C10	Phase 2	[10]
TT-100	DMZE6Y9	Non-small-cell lung cancer	2C25.Y	Phase 2	[11]
AMG 479	DM0DRAZ	Breast cancer	2C60-2C65	Phase 2	[12]
VPI-2690B	DMUQZT4	Diabetic nephropathy	GB61.Z	Phase 2	[13]
AXL-1717	DMTQ1Y3	Solid tumour/cancer	2A00-2F9Z	Phase 2	[14]
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Drug(s) Targeting Insulin receptor (INSR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Meglitinides	DM1OFHN	Type-2 diabetes	5A11	Approved	[15]
Human neutral insulin	DMA5OBU	Diabetic complication	5A2Y	Approved	[16]
Insulin Lyspro recombinant	DM5XHVR	Diabetic complication	5A2Y	Approved	[16]
Insulin, porcine	DMO95XI	Diabetic complication	5A2Y	Approved	[17]
Insulin recombinant	DMYVP5G	Diabetic complication	5A2Y	Approved	[16]
Metformin arginine-hemisuccinimide	DMTPAM3	Type-2 diabetes	5A11	Approved	[18]
Insulin-lispro	DM4O90W	Diabetic complication	5A2Y	Approved	[19]
Insulin-glulisine	DMQI0FU	Diabetic complication	5A2Y	Approved	[20]
Ryzodeq	DMOFP18	Type-2 diabetes	5A11	Approved	[21]
NN5401	DM0QV27	Diabetic complication	5A2Y	Phase 3	[21]
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Drug(s) Affected By Apoptosis-inducing factor 1, mitochondrial (AIFM1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[22]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[23]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[24]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[25]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[26]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[27]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[28]
Clonidine	DM6RZ9Q	Attention deficit hyperactivity disorder	6A05.Z	Approved	[29]
Acocantherin	DM7JT24	Atrial fibrillation	BC81.3	Approved	[30]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[31]
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Drug(s) Affected By Diablo IAP-binding mitochondrial protein (DIABLO)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[32]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[23]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[24]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[33]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[34]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[35]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[36]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[37]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[38]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[39]
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Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas

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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]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Apoptosis-inducing factor 1, mitochondrial (AIFM1)	OTKPWB7Q	AIFM1_HUMAN	Protein Interaction/Cellular Processes	[4]
Diablo IAP-binding mitochondrial protein (DIABLO)	OTHJ9MCZ	DBLOH_HUMAN	Protein Interaction/Cellular Processes	[4]

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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-administration of NVP-AEW541 and dasatinib induces mitochondrial-mediated apoptosis through Bax activation in malignant human glioma cell lines. Int J Oncol. 2010 Sep;37(3):633-43. doi: 10.3892/ijo_00000712.
5	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
6	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.
7	2005 approvals: Safety first. Nature Reviews Drug Discovery 5, 92-93 (February 2006).
8	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.
9	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.
10	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.
11	BiPar Sciences Co-founder Reunites Management Team At TriAct Therapeutics to Advance Clinical Stage Cancer Programs. TriAct Therapeutics. Sept. 10, 2009.
12	Clinical pipeline report, company report or official report of Amgen (2009).
13	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
14	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.
15	New drugs for type 2 diabetes mellitus: what is their place in therapy Drugs. 2008;68(15):2131-62.
16	Knockouts model the 100 best-selling drugs--will they model the next 100 Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
17	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.
18	Metformin (Glucophage) inhibits tyrosine phosphatase activity to stimulate the insulin receptor tyrosine kinase. Biochem Pharmacol. 2004 Jun 1;67(11):2081-91.
19	Hope for insulin mimetic oral antidiabetic drugs. Eur J Endocrinol. 1999 Dec;141(6):561-2.
20	Insulin glulisine: a review of its use in the management of diabetes mellitus. Drugs. 2009;69(8):1035-57.
21	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).
22	DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
23	Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
24	Apoptotic signaling pathways induced by nitric oxide in human lymphoblastoid cells expressing wild-type or mutant p53. Cancer Res. 2004 May 1;64(9):3022-9. doi: 10.1158/0008-5472.can-03-1880.
25	Sulindac activates nuclear translocation of AIF, DFF40 and endonuclease G but not induces oligonucleosomal DNA fragmentation in HT-29 cells. Life Sci. 2005 Sep 2;77(16):2059-70. doi: 10.1016/j.lfs.2005.04.021.
26	Quercetin induced cell apoptosis and altered gene expression in AGS human gastric cancer cells. Environ Toxicol. 2018 Nov;33(11):1168-1181. doi: 10.1002/tox.22623. Epub 2018 Aug 27.
27	Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
28	Arsenic trioxide-induced death of neuroblastoma cells involves activation of Bax and does not require p53. Clin Cancer Res. 2004 May 1;10(9):3179-88. doi: 10.1158/1078-0432.ccr-03-0309.
29	Clonidine Induces Apoptosis of Human Corneal Epithelial Cells through Death Receptors-Mediated, Mitochondria-Dependent Signaling Pathway. Toxicol Sci. 2017 Mar 1;156(1):252-260. doi: 10.1093/toxsci/kfw249.
30	Ouabain induces apoptotic cell death in human prostate DU 145 cancer cells through DNA damage and TRAIL pathways. Environ Toxicol. 2019 Dec;34(12):1329-1339. doi: 10.1002/tox.22834. Epub 2019 Aug 21.
31	Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
32	Gingival Stromal Cells as an In Vitro Model: Cannabidiol Modulates Genes Linked With Amyotrophic Lateral Sclerosis. J Cell Biochem. 2017 Apr;118(4):819-828. doi: 10.1002/jcb.25757. Epub 2016 Nov 28.
33	Statin-triggered cell death in primary human lung mesenchymal cells involves p53-PUMA and release of Smac and Omi but not cytochrome c. Biochim Biophys Acta. 2010 Apr;1803(4):452-67. doi: 10.1016/j.bbamcr.2009.12.005. Epub 2010 Jan 4.
34	Multifaceted preventive effects of single agent quercetin on a human prostate adenocarcinoma cell line (PC-3): implications for nutritional transcriptomics and multi-target therapy. Med Oncol. 2011 Dec;28(4):1395-404. doi: 10.1007/s12032-010-9603-3. Epub 2010 Jul 2.
35	Combination of all-trans retinoic acid and taxol regressed glioblastoma T98G xenografts in nude mice. Apoptosis. 2007 Nov;12(11):2077-87. doi: 10.1007/s10495-007-0116-2. Epub 2007 Aug 16.
36	Role of mitochondria in aspirin-induced apoptosis in human gastric epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2005 Oct;289(4):G731-8. doi: 10.1152/ajpgi.00150.2005. Epub 2005 Jun 23.
37	THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
38	Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
39	Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.