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

General Information of Drug (ID: DMF0SPB)

• Drug Name: AG 1024 Drug Info
• Synonyms: tyrphostin AG 1024; AG-1024; AG1024

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 2044
  ChEBI ID: CHEBI:93757
  CAS Number: CAS 65678-07-1
  TTD Drug ID: DMF0SPB

Molecule-Related Drug Atlas

Drug(s) Targeting IGF1R messenger RNA (IGF1R mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ATL-1101	DM4XZU2	Psoriatic disorder	EA90	Preclinical	[4]
GSK-1838705A	DM4HLK3	Discovery agent	N.A.	Investigative	[5]
AZD3463	DMAX9C3	Discovery agent	N.A.	Investigative	[6]
PQ401	DMVNHTE	Discovery agent	N.A.	Investigative	[7]
GSK1511931	DMZUTXW	Discovery agent	N.A.	Investigative	[8]

Drug(s) Affected By Cytochrome P450 1A1 (CYP1A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amodiaquine	DME4RA8	Malaria	1F40-1F45	Approved	[9]
Riluzole	DMECBWN	Amyotrophic lateral sclerosis	8B60.0	Approved	[10]
Flutamide	DMK0O7U	Prostate cancer	2C82.0	Approved	[11]
Menadione	DMSJDTY	Vitamin K deficiency	5B59	Approved	[12]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[13]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[14]
Ethacrynic acid	DM60QMR	Edema	MG29	Approved	[15]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[16]
Ethinyl Estradiol	DMODJ40	Acne vulgaris	ED80	Approved	[17]
Clofibrate	DMPC1J7	Dysbetalipoproteinemia	5C80.2	Approved	[18]

Drug(s) Affected By RAC-alpha serine/threonine-protein kinase (AKT1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Capivasertib	DM9SKW8	Breast cancer	2C60-2C65	Approved	[19]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[20]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[21]
Beta-carotene	DM0RXBT	Vitamin deficiency	5B55-5B71	Approved	[22]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[23]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[24]
Imiquimod	DM1TMA3	Alopecia areata	ED70.2	Approved	[25]
Selenium	DM25CGV	N. A.	N. A.	Approved	[26]
Methimazole	DM25FL8	Hyperthyroidism	5A02	Approved	[27]
Ribavirin	DMEYLH9	Hepatitis C virus infection	1E51.1	Approved	[28]

Drug(s) Affected By Aryl hydrocarbon receptor (AHR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[29]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[30]
Citalopram	DM2G9AE	Acute coronary syndrome	BA41	Approved	[31]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[32]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[33]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[34]
Omeprazole	DM471KJ	Cystic fibrosis	CA25	Approved	[35]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[36]
Rifampicin	DM5DSFZ	Non-insulin dependent diabetes	5A11	Approved	[37]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[38]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
IGF1R messenger RNA (IGF1R mRNA)	TTQFBMY	IGF1R_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Aryl hydrocarbon receptor (AHR)	OTFE4EYE	AHR_HUMAN	Gene/Protein Processing	[2]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Gene/Protein Processing	[2]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Post-Translational Modifications	[3]

References

• [1] Specific inhibition of insulin-like growth factor-1 and insulin receptor tyrosine kinase activity and biological function by tyrphostins. Endocrinology. 1997 Apr;138(4):1427-33.
• [2] Tyrphostin AG1024 downregulates aryl hydrocarbon receptor (AhR) expression in an IGF1R and IR-independent manner. Toxicol Lett. 2022 May 1;360:62-70. doi: 10.1016/j.toxlet.2022.02.003. Epub 2022 Feb 8.
• [3] P2Y12 receptor signalling towards PKB proceeds through IGF-I receptor cross-talk and requires activation of Src, Pyk2 and Rap1. Cell Signal. 2006 Aug;18(8):1169-81. doi: 10.1016/j.cellsig.2005.09.005. Epub 2005 Oct 19.
• [4] Clinical pipeline report, company report or official report of Antisense Therapeutics.
• [5] Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol. 2011 Oct 30;29(11):1046-51.
• [6] 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: 1801).
• [7] Diarylureas are small-molecule inhibitors of insulin-like growth factor I receptor signaling and breast cancer cell growth. Mol Cancer Ther. 2006 Apr;5(4):1079-86.
• [8] Optimization of a series of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine inhibitors of IGF-1R: elimination of an acid-mediated decomposition pathway. Bioorg Med Chem Lett. 2009 Jan 15;19(2):373-7.
• [9] Cytochrome P450 1A1/2 induction by antiparasitic drugs: dose-dependent increase in ethoxyresorufin O-deethylase activity and mRNA caused by quinine, primaquine and albendazole in HepG2 cells. Eur J Clin Pharmacol. 2002 Nov;58(8):537-42.
• [10] Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.
• [11] Anti-androgenic effect of 6-formylindolo[3,2-b]carbazole (FICZ) in LNCaP cells is mediated by the aryl hydrocarbon-androgen receptors cross-talk. Steroids. 2020 Jan;153:108508. doi: 10.1016/j.steroids.2019.108508. Epub 2019 Oct 3.
• [12] Pharmacologic profiling of human and rat cytochrome P450 1A1 and 1A2 induction and competition. Arch Toxicol. 2008 Dec;82(12):909-21.
• [13] Effect of CYP1A1 gene polymorphisms on estrogen metabolism and bone density. J Bone Miner Res. 2005 Feb;20(2):232-9. doi: 10.1359/JBMR.041110. Epub 2004 Nov 16.
• [14] Increased sensitivity for troglitazone-induced cytotoxicity using a human in vitro co-culture model. Toxicol In Vitro. 2009 Oct;23(7):1387-95.
• [15] Isoform-specific induction of a human aldo-keto reductase by polycyclic aromatic hydrocarbons (PAHs), electrophiles, and oxidative stress: implications for the alternative pathway of PAH activation catalyzed by human dihydrodiol dehydrogenase. Cancer Res. 1999 Feb 1;59(3):607-14.
• [16] Gene expression changes in human small airway epithelial cells exposed to Delta9-tetrahydrocannabinol. Toxicol Lett. 2005 Aug 14;158(2):95-107.
• [17] The metallohormone cadmium modulates AhR-associated gene expression in the small intestine of rats similar to ethinyl-estradiol. Arch Toxicol. 2013 Apr;87(4):633-43.
• [18] Evidence for a new human CYP1A1 regulation pathway involving PPAR-alpha and 2 PPRE sites. Gastroenterology. 2004 Nov;127(5):1436-45.
• [19] Inhibition of cholesterol metabolism underlies synergy between mTOR pathway inhibition and chloroquine in bladder cancer cells. Oncogene. 2016 Aug 25;35(34):4518-28. doi: 10.1038/onc.2015.511. Epub 2016 Feb 8.
• [20] Nicotine-induced survival signaling in lung cancer cells is dependent on their p53 status while its down-regulation by curcumin is independent. Mol Cancer. 2010 Aug 20;9:220.
• [21] Role of miRNA in the regulation of cannabidiol-mediated apoptosis in neuroblastoma cells. Oncotarget. 2019 Jan 1;10(1):45-59. doi: 10.18632/oncotarget.26534. eCollection 2019 Jan 1.
• [22] -Carotene Induces Apoptosis in Human Esophageal Squamous Cell Carcinoma Cell Lines via the Cav-1/AKT/NF-B Signaling Pathway. J Biochem Mol Toxicol. 2016 Mar;30(3):148-57. doi: 10.1002/jbt.21773. Epub 2016 Jan 6.
• [23] Dihydromyricetin suppresses tumor growth via downregulation of the EGFR/Akt/survivin signaling pathway. J Biochem Mol Toxicol. 2023 Jun;37(6):e23328. doi: 10.1002/jbt.23328. Epub 2023 Feb 19.
• [24] Oxidative stress induces parallel autophagy and mitochondria dysfunction in human glioma U251 cells. Toxicol Sci. 2009 Aug;110(2):376-88. doi: 10.1093/toxsci/kfp101. Epub 2009 May 18.
• [25] Effect of toll-like receptor 7 and 9 targeted therapy to prevent the development of hepatocellular carcinoma. Liver Int. 2015 Mar;35(3):1063-76. doi: 10.1111/liv.12626. Epub 2014 Jul 30.
• [26] 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.
• [27] 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.
• [28] Ribavirin augments doxorubicin's efficacy in human hepatocellular carcinoma through inhibiting doxorubicin-induced eIF4E activation. J Biochem Mol Toxicol. 2018 Jan;32(1). doi: 10.1002/jbt.22007. Epub 2017 Nov 7.
• [29] Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
• [30] Oxidative stress modulates expression of immune checkpoint genes via activation of AhR signaling. Toxicol Appl Pharmacol. 2022 Dec 15;457:116314. doi: 10.1016/j.taap.2022.116314. Epub 2022 Nov 9.
• [31] Profiling of enantiopure drugs towards aryl hydrocarbon (AhR), glucocorticoid (GR) and pregnane X (PXR) receptors in human reporter cell lines. Chem Biol Interact. 2014 Feb 5;208:64-76. doi: 10.1016/j.cbi.2013.11.018. Epub 2013 Dec 6.
• [32] Involvement of cytoskeleton in AhR-dependent CYP1A1 expression. Curr Drug Metab. 2006 Apr;7(3):301-13. doi: 10.2174/138920006776359310.
• [33] Sulindac and its metabolites induce carcinogen metabolizing enzymes in human colon cancer cells. Int J Cancer. 2008 Mar 1;122(5):990-8.
• [34] Quercetin, quercetin glycosides and taxifolin differ in their ability to induce AhR activation and CYP1A1 expression in HepG2 cells. Phytother Res. 2012 Nov;26(11):1746-52.
• [35] Omeprazole inhibits pancreatic cancer cell invasion through a nongenomic aryl hydrocarbon receptor pathway. Chem Res Toxicol. 2015 May 18;28(5):907-18.
• [36] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [37] Expression and inducibility of cytochrome P450s (CYP1A1, 2B6, 2E1, 3A4) in human cord blood CD34(+) stem cell-derived differentiating neuronal cells. Toxicol Sci. 2012 Oct;129(2):392-410.
• [38] Induction of paraoxonase 1 and apolipoprotein A-I gene expression by aspirin. J Lipid Res. 2008 Oct;49(10):2142-8.