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

General Information of Drug (ID: DMR4HIW)

• Drug Name: Insulin-glargine Drug Info
• Synonyms: Glargine; Lantus; SoloStar; SoloStar [Insulin delivery pen]; A21-Gly-B31-Arg-B32-Arg-insulin

Indication

Disease Entry	ICD 11	Status	REF
Diabetic complication	5A2Y	Approved	[1]
Non-insulin dependent diabetes	5A11	Approved	[2]
Malaria	1F40-1F45	Phase 3	[3]
Type-1 diabetes	5A10	Phase 3	[4]
Type-2 diabetes	5A11	Application submitted	[5]

• Therapeutic Class: Hypoglycemic Agents
• Cross-matching ID:
  PubChem CID: 118984454
  CAS Number: CAS 160337-95-1
  TTD Drug ID: DMR4HIW

Molecule-Related Drug Atlas

Drug(s) Targeting Insulin (INS)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Inulin	DM1Y2JH	Measure kidney function	MG02	Approved	[6]
Insulin Zinc Susp Recombinant Human	DM6MO9X	Diabetic complication	5A2Y	Approved	[6]
Insulin Susp Isophane Recombinant Human	DMW8KI7	Diabetic complication	5A2Y	Approved	[6]
Insulin determir	DM79NZ5	Diabetic complication	5A2Y	Approved	[8]
Insulin Susp Protamine Zinc Beef/Pork	DM0NATE	Diabetic complication	5A2Y	Approved	[6]
Insulin-aspart	DMX7V28	Diabetic complication	5A2Y	Approved	[6]
Insulin degludec	DMPL395	Type-1/2 diabetes	5A10-5A11	Approved	[9]
Insulin-detemir	DMOA4VW	Type-1/2 diabetes	5A10-5A11	Approved	[6]
LY2963016	DMEZ0H5	Type-1/2 diabetes	5A10-5A11	Phase 3	[10]
SAR342434	DMR0EWV	Diabetic complication	5A2Y	Phase 3	[11]

Drug(s) Affected By Insulin receptor (INSR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[12]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[13]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[14]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[15]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[16]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[17]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[18]
Rosiglitazone	DMILWZR	Chronic kidney disease	GB61	Approved	[19]
Phenytoin	DMNOKBV	Epilepsy	8A60-8A68	Approved	[20]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[21]

Drug(s) Affected By Insulin-like growth factor 1 receptor (IGF1R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[22]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[23]
Methimazole	DM25FL8	Hyperthyroidism	5A02	Approved	[24]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[25]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[26]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[27]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[28]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[29]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[29]
Clodronate	DM9Y6X7	Hypercalcaemia	5B91.0	Approved	[30]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Insulin (INS)	TTZOPHG	INS_HUMAN	Modulator	[6]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Insulin receptor (INSR)	OTTY341H	INSR_HUMAN	Post-Translational Modifications	[7]
Insulin-like growth factor 1 receptor (IGF1R)	OTXJIF13	IGF1R_HUMAN	Post-Translational Modifications	[7]

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: 7572).
• [2] Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial. JAMA. 2022 Feb 8;327(6):534-545.
• [3] ClinicalTrials.gov (NCT02059161) A Study of the Safety and Efficacy of MK-1293 Compared to Lantus in Participants With Type 1 Diabetes Mellitus (T1DM) (MK-1293-003). U.S. National Institutes of Health.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [7] IR and IGF-1R expression affects insulin induced proliferation and DNA damage. Toxicol In Vitro. 2017 Mar;39:68-74. doi: 10.1016/j.tiv.2016.11.011. Epub 2016 Nov 22.
• [8] 2005 approvals: Safety first. Nature Reviews Drug Discovery 5, 92-93 (February 2006).
• [9] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [10] Efficacy and safety of LY2963016 insulin glargine compared with insulin glargine (Lantus ) in patients with type 1 diabetes in a randomized controlled trial: the ELEMENT 1 study. Diabetes Obes Metab.2015 Aug;17(8):726-33.
• [11] Biosimilar insulins: a European perspective. Diabetes Obes Metab. 2015 May; 17(5): 445-451.
• [12] Fanconi anemia links reactive oxygen species to insulin resistance and obesity. Antioxid Redox Signal. 2012 Oct 15;17(8):1083-98. doi: 10.1089/ars.2011.4417. Epub 2012 Jun 25.
• [13] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [14] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [15] [Testosterone's role in regulating expression of genes of several proliferation factors]. Tsitologiia. 2006;48(10):856-61.
• [16] 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.
• [17] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [18] Sulfasalazine and BAY 11-7082 interfere with the nuclear factor-kappa B and I kappa B kinase pathway to regulate the release of proinflammatory cytokines from human adipose tissue and skeletal muscle in vitro. Endocrinology. 2005 Mar;146(3):1491-7. doi: 10.1210/en.2004-0809. Epub 2004 Nov 24.
• [19] Methamphetamine exposure upregulates the amyloid precursor protein and hyperphosphorylated tau expression: The roles of insulin signaling in SH-SY5Y cell line. J Toxicol Sci. 2019;44(7):493-503. doi: 10.2131/jts.44.493.
• [20] Role of phenytoin in wound healing: microarray analysis of early transcriptional responses in human dermal fibroblasts. Biochem Biophys Res Commun. 2004 Feb 13;314(3):661-6. doi: 10.1016/j.bbrc.2003.12.146.
• [21] Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
• [22] Estrogen utilization of IGF-1-R and EGF-R to signal in breast cancer cells. J Steroid Biochem Mol Biol. 2010 Feb 28;118(4-5):219-30. doi: 10.1016/j.jsbmb.2009.09.018. Epub 2009 Oct 6.
• [23] Implication of the insulin-like growth factor-IR pathway in the resistance of non-small cell lung cancer cells to treatment with gefitinib. Clin Cancer Res. 2007 May 1;13(9):2795-803. doi: 10.1158/1078-0432.CCR-06-2077.
• [24] Low-expressional IGF1 mediated methimazole-induced liver developmental toxicity in fetal mice. Toxicology. 2018 Sep 1;408:70-79. doi: 10.1016/j.tox.2018.07.004. Epub 2018 Jul 7.
• [25] Simvastatin inhibits the proliferation of human prostate cancer PC-3 cells via down-regulation of the insulin-like growth factor 1 receptor. Biochem Biophys Res Commun. 2008 Jul 25;372(2):356-61. doi: 10.1016/j.bbrc.2008.05.043. Epub 2008 May 19.
• [26] 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.
• [27] Arsenic trioxide and cisplatin synergism increase cytotoxicity in human ovarian cancer cells: therapeutic potential for ovarian cancer. Cancer Sci. 2009 Dec;100(12):2459-64.
• [28] Delta9-tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription. Mol Hum Reprod. 2006 May;12(5):321-33. doi: 10.1093/molehr/gal036. Epub 2006 Apr 5.
• [29] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [30] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.