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

General Information of Drug (ID: DM6YWBF)

• Drug Name: Herbimycin A Drug Info
• Synonyms: Herbimycin; Herbimycin A from Streptomyces hygroscopicus; Antibiotic Tan 420F; [(2R,3S,5S,6R,7S,8E,10S,11S,12E,14E)-2,5,6,11-tetramethoxy-3,7,9,15-tetramethyl-16,20,22-trioxo-17-azabicyclo[16.3.1]docosa-1(21),8,12,14,18-pentaen-10-yl] carbamate; [(2R,3S,5S,6R,7S,8E,10S,11S,12Z,14E)-2,5,6,11-tetramethoxy-3,7,9,15-tetramethyl-16,20,22-trioxo-17-azabicyclo[16.3.1]docosa-1(21),8,12,14,18-pentaen-10-yl] carbamate; (2,5,6,11-tetramethoxy-3,7,9,15-tetramethyl-16,20,22-trioxo-17-azabicyclo[16.3.1]docosa-1(21),8,12,14,18-pentaen-10-yl) carbamate

Indication

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

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  PubChem CID: 5311102
  ChEBI ID: CHEBI:5674
  CAS Number: CAS 70563-58-5
  TTD Drug ID: DM6YWBF

Molecule-Related Drug Atlas

Drug(s) Targeting Proto-oncogene c-Src (SRC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dasatinib	DMJV2EK	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[5]
Bosutinib	DMTI8YE	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[5]
SKI-758	DMQ8E9R	Ischemia	8B10-8B11	Approved	[6]
AL3818	DM3WP0N	Alveolar soft part sarcoma	2A60-2C35	Phase 3	[7]
CP-868596	DMZIM37	Gastrointestinal cancer	2C11	Phase 3	[7]
Masitinib	DMRSNEU	Amyotrophic lateral sclerosis	8B60.0	Phase 3	[8]
KX-01	DMF0NA9	Actinic keratosis	EK90.0	Phase 3	[9]
Saracatinib	DMBLHGP	Hematologic tumour	2B33.Y	Phase 2	[10]
TPX-0046	DMIVE67	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[11]
ISIS-CRP	DMQDUG4	Cardiovascular disease	BA00-BE2Z	Phase 1	[12]

Drug(s) Affected By Voltage-dependent T-type calcium channel subunit alpha-1H (CACNA1H)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Leflunomide	DMR8ONJ	Arthritis	FA20	Approved	[13]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[14]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[15]
Menthol	DMG2KW7	Back pain	ME84.Z	Approved	[16]
Niclosamide	DMJAGXQ	Cestodes infection	1F70-1F76	Approved	[17]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[18]
Arsenic	DMTL2Y1	N. A.	N. A.	Approved	[19]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[20]
Triclosan	DMZUR4N	Malaria	1F40-1F45	Approved	[21]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[22]

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	[23]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[24]
Citalopram	DM2G9AE	Acute coronary syndrome	BA41	Approved	[25]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[26]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[27]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[28]
Omeprazole	DM471KJ	Cystic fibrosis	CA25	Approved	[29]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[30]
Rifampicin	DM5DSFZ	Non-insulin dependent diabetes	5A11	Approved	[31]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[32]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Proto-oncogene c-Src (SRC)	TT6PKBN	SRC_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Aryl hydrocarbon receptor (AHR)	OTFE4EYE	AHR_HUMAN	Gene/Protein Processing	[3]
Voltage-dependent T-type calcium channel subunit alpha-1H (CACNA1H)	OTM705TH	CAC1H_HUMAN	Gene/Protein Processing	[4]

References

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• [3] The inhibitory mechanisms of the tyrosine kinase inhibitors herbimycin a, genistein, and tyrphostin B48 with regard to the function of the aryl hydrocarbon receptor in Caco-2 cells. Biosci Biotechnol Biochem. 2010;74(1):36-43. doi: 10.1271/bbb.90438. Epub 2010 Jan 7.
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• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [15] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [16] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [17] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [18] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [19] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [20] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [21] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [22] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [23] Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
• [24] 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.
• [25] 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.
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• [27] Sulindac and its metabolites induce carcinogen metabolizing enzymes in human colon cancer cells. Int J Cancer. 2008 Mar 1;122(5):990-8.
• [28] 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.
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• [30] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
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• [32] Induction of paraoxonase 1 and apolipoprotein A-I gene expression by aspirin. J Lipid Res. 2008 Oct;49(10):2142-8.