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

General Information of Drug (ID: DMHKZLF)

• Drug Name: OSI-906 Drug Info
• 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]

• Cross-matching ID:
  PubChem CID: 11640390
  ChEBI ID: CHEBI:91402
  CAS Number: CAS 867160-71-2
  TTD Drug ID: DMHKZLF

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	[4]
Mecasermin	DM1O3BY	Growth failure	LD2F.1Y	Approved	[5]
Somatomedin-1	DMZ9FAO	Hormone deficiency	5A61.1	Approved	[6]
Rinfabate	DML9FD4	Solid tumour/cancer	2A00-2F9Z	Phase 2/3	[7]
MM-141	DM2RJ4D	Pancreatic cancer	2C10	Phase 2	[8]
TT-100	DMZE6Y9	Non-small-cell lung cancer	2C25.Y	Phase 2	[9]
AMG 479	DM0DRAZ	Breast cancer	2C60-2C65	Phase 2	[10]
VPI-2690B	DMUQZT4	Diabetic nephropathy	GB61.Z	Phase 2	[11]
AXL-1717	DMTQ1Y3	Solid tumour/cancer	2A00-2F9Z	Phase 2	[12]
R1507	DMIUS5X	Graves ophthalmopathy	9C82.3	Phase 2	[13]

Drug(s) Affected By Transferrin receptor protein 1 (TFRC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[14]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[15]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[16]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[17]
Rofecoxib	DM3P5DA	Osteoarthritis	FA00-FA05	Approved	[18]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[19]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[20]
Acetic Acid, Glacial	DM4SJ5Y	infection in the ear canal	AA0Y	Approved	[21]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[22]
Hydroquinone	DM6AVR4	Melasma	ED60.1	Approved	[23]

Drug(s) Affected By HLA class I histocompatibility antigen, alpha chain G (HLA-G)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Selenium	DM25CGV	N. A.	N. A.	Approved	[24]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[25]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[26]
Omeprazole	DM471KJ	Cystic fibrosis	CA25	Approved	[25]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[27]
Erythromycin	DM4K7GQ	Acne vulgaris	ED80	Approved	[25]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[20]
Lisinopril	DMUOK4C	Chronic heart failure	BD1Z	Approved	[25]
Rifampicin	DM5DSFZ	Non-insulin dependent diabetes	5A11	Approved	[25]
Glimepiride	DM5FSJA	Diabetic complication	5A2Y	Approved	[25]

Drug(s) Affected By Proliferation marker protein Ki-67 (MKI67)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Levonorgestrel	DM1DP7T	Atypical endometrial hyperplasia		Approved	[28]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[29]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[30]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[31]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[32]
Remdesivir	DMBFZ6L	Coronavirus Disease 2019 (COVID-19)	1D6Y	Approved	[33]
Chlorpromazine	DMBGZI3	Acute intermittent hepatic porphyria	5C58.11	Approved	[34]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[35]
Thalidomide	DM70BU5	Adult T-cell leukemia/lymphoma		Approved	[36]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[37]

Drug(s) Affected By Tumor protein 63 (TP63)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[38]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[39]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[40]
Panobinostat	DM58WKG	Chronic graft versus host disease		Approved	[41]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[42]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[43]
Melphalan	DMOLNHF	Hematologic disease	3C0Z	Approved	[44]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[45]
Topotecan	DMP6G8T	Central nervous system neoplasm		Approved	[46]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[47]

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	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
HLA class I histocompatibility antigen, alpha chain G (HLA-G)	OTMLK1KN	HLAG_HUMAN	Gene/Protein Processing	[3]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Gene/Protein Processing	[3]
Transferrin receptor protein 1 (TFRC)	OT8ZPBDL	TFR1_HUMAN	Gene/Protein Processing	[3]
Tumor protein 63 (TP63)	OT0WOOKQ	P63_HUMAN	Gene/Protein Processing	[3]

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] 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.
• [3] Screening of Organophosphate Flame Retardants with Placentation-Disrupting Effects in Human Trophoblast Organoid Model and Characterization of Adverse Pregnancy Outcomes in Mice. Environ Health Perspect. 2022 May;130(5):57002. doi: 10.1289/EHP10273. Epub 2022 May 3.
• [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).
• [14] Gene expression profiles with activation of the estrogen receptor alpha-selective estrogen receptor modulator complex in breast cancer cells expressing wild-type estrogen receptor. Cancer Res. 2002 Aug 1;62(15):4419-26.
• [15] Relationships and distinctions in iron-regulatory networks responding to interrelated signals. Blood. 2003 May 1;101(9):3690-8. doi: 10.1182/blood-2002-07-2140. Epub 2002 Sep 26.
• [16] Differential effects of statins on relevant functions of human monocyte-derived dendritic cells. J Leukoc Biol. 2006 Mar;79(3):529-38. doi: 10.1189/jlb.0205064. Epub 2005 Dec 30.
• [17] Quantitative proteomic analysis of HepG2 cells treated with quercetin suggests IQGAP1 involved in quercetin-induced regulation of cell proliferation and migration. OMICS. 2009 Apr;13(2):93-103. doi: 10.1089/omi.2008.0075.
• [18] Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain. Pain. 2007 Mar;128(1-2):136-47.
• [19] Retinoic acid-induced downmodulation of telomerase activity in human cancer cells. Exp Mol Pathol. 2005 Oct;79(2):108-17.
• [20] 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.
• [21] Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
• [22] Arsenic trioxide induces apoptosis of human monocytes during macrophagic differentiation through nuclear factor-kappaB-related survival pathway down-regulation. J Pharmacol Exp Ther. 2006 Jan;316(1):304-14. doi: 10.1124/jpet.105.092874. Epub 2005 Sep 20.
• [23] Phenolic metabolites of benzene inhibited the erythroid differentiation of K562 cells. Toxicol Lett. 2011 Jun 24;203(3):190-9. doi: 10.1016/j.toxlet.2011.03.012. Epub 2011 Mar 23.
• [24] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [25] Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
• [26] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [27] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [28] Effect of menstrual cycle and hormonal treatment on ki-67 and bcl-2 expression and adenomyosis. Gynecol Endocrinol. 2005 Mar;20(3):127-31. doi: 10.1080/09513590400021086.
• [29] Methotrexate modulates folate phenotype and inflammatory profile in EA.hy 926 cells. Eur J Pharmacol. 2014 Jun 5;732:60-7.
• [30] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [31] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [32] Effect of retinoic acid on gene expression in human conjunctival epithelium: secretory phospholipase A2 mediates retinoic acid induction of MUC16. Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4050-61.
• [33] An in vitro study on anti-carcinogenic effect of remdesivir in human ovarian cancer cells via generation of reactive oxygen species. Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221089257. doi: 10.1177/09603271221089257.
• [34] Effects of chlorpromazine with and without UV irradiation on gene expression of HepG2 cells. Mutat Res. 2005 Aug 4;575(1-2):47-60. doi: 10.1016/j.mrfmmm.2005.03.002. Epub 2005 Apr 26.
• [35] Mitophagy inhibits proliferation by decreasing cyclooxygenase-2 (COX-2) in arsenic trioxide-treated HepG2 cells. Environ Toxicol Pharmacol. 2016 Jul;45:212-21.
• [36] Thalidomide suppresses angiogenesis and immune evasion via lncRNA FGD5-AS1/miR-454-3p/ZEB1 axis-mediated VEGFA expression and PD-1/PD-L1 checkpoint in NSCLC. Chem Biol Interact. 2021 Nov 1;349:109652. doi: 10.1016/j.cbi.2021.109652. Epub 2021 Sep 11.
• [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] 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.
• [39] Flavones and flavonols exert cytotoxic effects on a human oesophageal adenocarcinoma cell line (OE33) by causing G2/M arrest and inducing apoptosis. Food Chem Toxicol. 2008 Jun;46(6):2042-53. doi: 10.1016/j.fct.2008.01.049. Epub 2008 Feb 7.
• [40] Activation of PPAR and inhibition of cell proliferation reduces key proteins associated with the basal subtype of bladder cancer in As3+-transformed UROtsa cells. PLoS One. 2020 Aug 21;15(8):e0237976. doi: 10.1371/journal.pone.0237976. eCollection 2020.
• [41] Induction of TAp63 by histone deacetylase inhibitors. Biochem Biophys Res Commun. 2010 Jan 22;391(4):1748-51. doi: 10.1016/j.bbrc.2009.12.147. Epub 2009 Dec 30.
• [42] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [43] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [44] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [45] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [46] p63 involvement in poly(ADP-ribose) polymerase 1 signaling of topoisomerase I-dependent DNA damage in carcinoma cells. Biochem Pharmacol. 2013 Apr 1;85(7):999-1006. doi: 10.1016/j.bcp.2013.01.019. Epub 2013 Jan 29.
• [47] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.