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

General Information of Drug (ID: DM8IC5H)

• Drug Name: TRICIRIBINE Drug Info
• Synonyms: NSC154020; Akt Inhibitor V, Triciribine; MLS002702033; Akt/PKB Signaling Inhibitor-2; NSC-154020; TCN; Akt inhibitor V; AC1Q7CGY; AC1L6DVE; tricyclic nucleoside (TCN); SCHEMBL61269; GTPL5920; CHEMBL1892348; CHEBI:91697; HMS3268N05; HMS3654C06; HMS3229A09; HSCI1_000386; CCG-206732; 5-methyl-1-pentofuranosyl-1,5-dihydro-1,4,5,6,8-pentaazaacenaphthylen-3-amine; SMR001565606; SC-89664; NCI60_001091; Akt/protein kinase B signaling inhibitor-2; BRD-A42649439-001-01-0; BRD-A42649439-001-02-8; 1,5,6,8-Pentaazaacennaphthylen-3-amine, 1,5-dih

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[1]

• Cross-matching ID:
  PubChem CID: 65399
  ChEBI ID: CHEMBL331237
  CAS Number: CAS 35943-35-2
  TTD Drug ID: DM8IC5H
  INTEDE Drug ID: DR1821

Molecule-Related Drug Atlas

Drug(s) Targeting Human immunodeficiency virus Reverse transcriptase (HIV RT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[6]
Nevirapine	DM6HX9B	Human immunodeficiency virus infection	1C62	Approved	[7]
Zalcitabine	DMH7MUV	Human immunodeficiency virus infection	1C62	Approved	[8]
Tenofovir	DM1IS6U	Chronic hepatitis B virus infection		Approved	[6]
Lamivudine	DMI347A	Chronic HBV infection	1E51.0Z	Approved	[9]
Abacavir	DMMN36E	Human immunodeficiency virus infection	1C62	Approved	[10]
Delavirdine	DM3NF5G	Human immunodeficiency virus infection	1C62	Approved	[9]
Efavirenz	DMC0GSJ	Human immunodeficiency virus infection	1C62	Approved	[9]
Rilpivirine	DMJ0QOW	Human immunodeficiency virus infection	1C62	Approved	[11]
Etravirine	DMGV8QU	Human immunodeficiency virus-1 infection	1C62	Approved	[12]

Drug(s) Affected By Follitropin subunit beta (FSHB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Crizotinib	DM4F29C	Non-small-cell lung cancer	2C25.Y	Approved	[13]
Cyclophosphamide	DM4O2Z7	Advanced cancer	2A00-2F9Z	Approved	[14]
Goserelin	DMAT8CG	Breast cancer	2C60-2C65	Approved	[15]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[16]
Cetrorelix	DMFD9Q6	Ovarian stimulation	LB45.1	Approved	[17]
Letrozole	DMH07Y3	Estrogen-receptor positive breast cancer		Approved	[18]
Cimetidine	DMH61ZB	Acid-reflux disorder	DA22	Approved	[19]
Risperidone	DMN6DXL	Bipolar I disorder		Approved	[20]
Ethinyl Estradiol	DMODJ40	Acne vulgaris	ED80	Approved	[21]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[22]

Drug(s) Affected By Poly polymerase 1 (PARP1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[23]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[24]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[25]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[26]
Citalopram	DM2G9AE	Acute coronary syndrome	BA41	Approved	[27]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[28]
Imipramine	DM2NUH3	Depression	6A70-6A7Z	Approved	[27]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[29]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[30]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[31]

Drug(s) Affected By Histone H2AX (H2AX)

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	[33]
Selenium	DM25CGV	N. A.	N. A.	Approved	[34]
Ribavirin	DMEYLH9	Hepatitis C virus infection	1E51.1	Approved	[35]
Etretinate	DM2CZFA	Keratosis	ED56	Approved	[36]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[37]
Dactinomycin	DM2YGNW	Adult kidney Wilms tumor		Approved	[38]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[39]
Lapatinib	DM3BH1Y	Breast cancer	2C60-2C65	Approved	[40]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[41]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Human immunodeficiency virus Reverse transcriptase (HIV RT)	TT84ETX	POL_HV1B1	Inhibitor	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Adenosine kinase (ADK) Main DME	DE7T5VX	ADK_HUMAN	Substrate	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Follitropin subunit beta (FSHB)	OTGLS283	FSHB_HUMAN	Gene/Protein Processing	[4]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Gene/Protein Processing	[5]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Gene/Protein Processing	[5]

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: 5920).
• [2] Design, synthesis and antiviral activity of novel 4,5-disubstituted 7-(beta-D-ribofuranosyl)pyrrolo[2,3-d][1,2,3]triazines and the novel 3-amino-5-... J Med Chem. 2005 Jun 2;48(11):3840-51.
• [3] Phosphorylation of triciribine is necessary for activity against HIV type 1. AIDS Res Hum Retroviruses. 1998 Oct 10;14(15):1315-22.
• [4] Inhibitory roles of prohibitin and chemerin in FSH-induced rat granulosa cell steroidogenesis. Endocrinology. 2013 Feb;154(2):956-67. doi: 10.1210/en.2012-1836. Epub 2012 Dec 18.
• [5] Metformin and epothilone A treatment up regulate pro-apoptotic PARP-1, Casp-3 and H2AX genes and decrease of AKT kinase level to control cell death of human hepatocellular carcinoma and ovary adenocarcinoma cells. Toxicol In Vitro. 2018 Mar;47:48-62. doi: 10.1016/j.tiv.2017.11.001. Epub 2017 Nov 5.
• [6] Antiviral drugs in current clinical use. J Clin Virol. 2004 Jun;30(2):115-33.
• [7] HIV-1 reverse transcriptase complex with DNA and nevirapine reveals non-nucleoside inhibition mechanism.Nat Struct Mol Biol.2012 Jan 22;19(2):253-9.
• [8] A peptide inhibitor of HIV-1 reverse transcriptase using alpha,beta-dehydro residues: a structure-based computer model. J Biomol Struct Dyn. 1998 Oct;16(2):347-54.
• [9] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [10] Quadruple nucleos(t)ide reverse transcriptase inhibitors-only regimen of tenofovir plus zidovudine/lamivudine/abacavir in heavily pre-treated HIV-1 infected patients: salvage therapy or backbone only Curr HIV Res. 2009 May;7(3):320-6.
• [11] Emerging antiviral drugs. Expert Opin Emerg Drugs. 2008 Sep;13(3):393-416.
• [12] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [13] Rapid-onset hypogonadism secondary to crizotinib use in men with metastatic nonsmall cell lung cancer. Cancer. 2012 Nov 1;118(21):5302-9. doi: 10.1002/cncr.27450. Epub 2012 Apr 4.
• [14] Suppression of spermatogenesis in patients with Beh?et's disease treated with cyclophosphamide and colchicine. Fertil Steril. 1981 Jul;36(1):76-80. doi: 10.1016/s0015-0282(16)45622-0.
• [15] [Kuntai capsule combined with gonadotropin releasing hormone agonist in treatment of moderate-severe endometriosis: a clinical observation]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2014 Nov;34(11):1288-91.
• [16] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [17] Pharmacokinetics of new testosterone transdermal therapeutic systems in gonadotropin-releasing hormone antagonist-suppressed normal men. Exp Clin Endocrinol Diabetes. 1999;107(1):63-9. doi: 10.1055/s-0029-1212075.
• [18] Aromatase inhibition, testosterone, and seizures. Epilepsy Behav. 2004 Apr;5(2):260-3. doi: 10.1016/j.yebeh.2003.12.001.
• [19] Male sexual dysfunction during treatment with cimetidine. Br Med J. 1979 Mar 10;1(6164):659. doi: 10.1136/bmj.1.6164.659.
• [20] Effect of risperidone and olanzapine on reproductive hormones, psychopathology and sexual functioning in male patients with schizophrenia. Psychoneuroendocrinology. 2009 Jan;34(1):129-39. doi: 10.1016/j.psyneuen.2008.08.015. Epub 2008 Oct 5.
• [21] Estrogens exert route- and dose-dependent effects on insulin-like growth factor (IGF)-binding protein-3 and the acid-labile subunit of the IGF ternary complex. J Clin Endocrinol Metab. 2000 May;85(5):1918-22. doi: 10.1210/jcem.85.5.6527.
• [22] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [23] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [24] Evidence of securin-mediated resistance to gefitinib-induced apoptosis in human cancer cells. Chem Biol Interact. 2013 Apr 25;203(2):412-22. doi: 10.1016/j.cbi.2013.03.011. Epub 2013 Mar 22.
• [25] Cigarette smoke and asbestos activate poly-ADP-ribose polymerase in alveolar epithelial cells. J Investig Med. 2001 Jan;49(1):68-76. doi: 10.2310/6650.2001.34092.
• [26] 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.
• [27] The antidepressants imipramine, clomipramine, and citalopram induce apoptosis in human acute myeloid leukemia HL-60 cells via caspase-3 activation. J Biochem Mol Toxicol. 1999;13(6):338-47. doi: 10.1002/(sici)1099-0461(1999)13:6<338::aid-jbt8>3.0.co;2-7.
• [28] Ciprofloxacin mediated cell growth inhibition, S/G2-M cell cycle arrest, and apoptosis in a human transitional cell carcinoma of the bladder cell line. Clin Cancer Res. 2000 Mar;6(3):891-900.
• [29] Investigation of molecular mechanisms underlying the antiproliferative effects of colchicine against PC3 prostate cancer cells. Toxicol In Vitro. 2021 Jun;73:105138. doi: 10.1016/j.tiv.2021.105138. Epub 2021 Mar 6.
• [30] Sulindac enhances adenoviral vector expressing mda-7/IL-24-mediated apoptosis in human lung cancer. Mol Cancer Ther. 2005 Feb;4(2):291-304.
• [31] Methotrexate induces poly(ADP-ribose) polymerase-dependent, caspase 3-independent apoptosis in subsets of proliferating CD4+ T cells. Clin Exp Immunol. 2007 May;148(2):288-95. doi: 10.1111/j.1365-2249.2007.03335.x. Epub 2007 Feb 7.
• [32] Cannabinoids synergize with carfilzomib, reducing multiple myeloma cells viability and migration. Oncotarget. 2016 Nov 22;7(47):77543-77557. doi: 10.18632/oncotarget.12721.
• [33] Hsa-let-7g miRNA regulates the anti-tumor effects of gastric cancer cells under oxidative stress through the expression of DDR genes. J Toxicol Sci. 2015 Jun;40(3):329-38. doi: 10.2131/jts.40.329.
• [34] 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.
• [35] Inhibition of cardiomyocyte differentiation of human induced pluripotent stem cells by Ribavirin: Implication for its cardiac developmental toxicity. Toxicology. 2020 Apr 15;435:152422. doi: 10.1016/j.tox.2020.152422. Epub 2020 Feb 26.
• [36] Synthesis and structure-activity relationships of new antiproliferative and proapoptotic retinoid-related biphenyl-4-yl-acrylic acids. Bioorg Med Chem. 2007 Jul 15;15(14):4863-75. doi: 10.1016/j.bmc.2007.04.057. Epub 2007 May 3.
• [37] Methotrexate induces apoptosis through p53/p21-dependent pathway and increases E-cadherin expression through downregulation of HDAC/EZH2. Biochem Pharmacol. 2011 Feb 15;81(4):510-7. doi: 10.1016/j.bcp.2010.11.014. Epub 2010 Nov 27.
• [38] Actinomycin D inhibits the expression of the cystine/glutamate transporter xCT via attenuation of CD133 synthesis in CD133(+) HCC. Chem Biol Interact. 2019 Aug 25;309:108713. doi: 10.1016/j.cbi.2019.06.026. Epub 2019 Jun 19.
• [39] Simvastatin and purine analogs have a synergic effect on apoptosis of chronic lymphocytic leukemia cells. Ann Hematol. 2010 Nov;89(11):1115-24. doi: 10.1007/s00277-010-0988-z. Epub 2010 May 25.
• [40] The involvement of hepatic cytochrome P450s in the cytotoxicity of lapatinib. Toxicol Sci. 2023 Dec 21;197(1):69-78. doi: 10.1093/toxsci/kfad099.
• [41] The isoflavonoids genistein and quercetin activate different stress signaling pathways as shown by analysis of site-specific phosphorylation of ATM, p53 and histone H2AX. DNA Repair (Amst). 2004 Mar 4;3(3):235-44. doi: 10.1016/j.dnarep.2003.10.014.