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

General Information of Drug (ID: DM1LGKP)

• Drug Name: Mevastatin Drug Info
• Synonyms: Mevastatin; compactin; 73573-88-3; ML-236B; Mevastatinum; Mevastatine; Mevastatina; Mevastatinum [INN-Latin]; Antibiotic ML 236B; Mevastatin [INN]; CS 500; Compactin (penicillium); Mevastatine [INN-French]; UNII-1UQM1K0W9X; ML 236 B; Mevastatina [INN-Spanish]; CCRIS 4505; 1UQM1K0W9X; CHEMBL54440; CHEBI:34848; [(1S,7S,8S,8aR)-8-[2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] (2S)-2-methylbutanoate; Mevastatin (Compactin); ML236B
• Cross-matching ID:
  PubChem CID: 64715
  ChEBI ID: CHEBI:34848
  CAS Number: CAS 73573-88-3
  TTD Drug ID: DM1LGKP
  INTEDE Drug ID: DR2217

Molecule-Related Drug Atlas

Drug(s) Targeting HMG-CoA reductase (HMGCR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pravastatin	DM6A0X7	Adult acute monocytic leukemia		Approved	[7]
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[8]
Cerivastatin	DMXCM7H	Hyperlipidaemia	5C80	Approved	[9]
PITAVASTATIN CALCIUM	DM1UJO0	Dyslipidemia	5C80-5C81	Approved	[10]
Rosuvastatin	DMMIQ7G	Arteriosclerosis	BD40	Approved	[11]
Fluvastatin	DM4MDJY	Arteriosclerosis	BD40	Approved	[8]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[12]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[8]
Lovastatin	DM9OZWQ	Arteriosclerosis	BD40	Approved	[13]
Teriflunomide	DMQ2FKJ	Hyperlipidaemia	5C80	Approved	[12]

Drug(s) Metabolized By Cytochrome P450 105D7 (cyp105)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[2]
NARINGENIN	DMHAZLM	N. A.	N. A.	Phase 1	[2]
Q-27137207	DML5KMT	N. A.	N. A.	Investigative	[2] , [3]

Drug(s) Affected By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Eplerenone	DMF0NQR	Heart failure	BD10-BD13	Approved	[14]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[15]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[16]
Voriconazole	DMAOL2S	Aspergillosis	1F20	Approved	[17]
Proguanil	DMBL79I	Malaria	1F40-1F45	Approved	[18]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[18]
Loratadine	DMF3AN7	Allergy	4A80-4A85	Approved	[19]
Nelfinavir mesylate	DMFX6G8	N. A.	N. A.	Approved	[20]
Capsaicin	DMGMF6V	Back pain	ME84.Z	Approved	[21]
Axitinib	DMGVH6N	Renal cell carcinoma	2C90	Approved	[22]

Drug(s) Affected By Bone morphogenetic protein 2 (BMP2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[23]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[4]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[24]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[25]
Panobinostat	DM58WKG	Chronic graft versus host disease		Approved	[26]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[27]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[28]
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[29]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[30]
Demecolcine	DMCZQGK	Solid tumour/cancer	2A00-2F9Z	Approved	[31]

Drug(s) Affected By Transforming protein RhoA (RHOA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[32]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[33]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[34]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[35]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[36]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[36]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[37]
Lovastatin	DM9OZWQ	Arteriosclerosis	BD40	Approved	[38]
Pamidronate	DMB4AVP	Bone Paget disease		Approved	[39]
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[40]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
HMG-CoA reductase (HMGCR)	TTPADOQ	HMDH_HUMAN	Antagonist	[1]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 105D7 (cyp105) Main DME	DECV2ME	CYP28_STRAW	Substrate	[2] , [3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Bone morphogenetic protein 2 (BMP2)	OT23T37S	BMP2_HUMAN	Gene/Protein Processing	[4]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Gene/Protein Processing	[5]
Transforming protein RhoA (RHOA)	OT6YOJ9N	RHOA_HUMAN	Post-Translational Modifications	[6]

References

• [1] Regulation of CYP2B6 and CYP3A expression by hydroxymethylglutaryl coenzyme A inhibitors in primary cultured human hepatocytes. Drug Metab Dispos. 2002 Dec;30(12):1400-5.
• [2] The metagenome of Caracolus marginella gut microbiome using culture independent approaches and shotgun sequencing. Data Brief. 2017 Nov 22;16:501-505.
• [3] Hydroxylation of Compactin (ML-236B) by CYP105D7 (SAV_7469) from Streptomyces avermitilis. J Microbiol Biotechnol. 2017 May 28;27(5):956-964.
• [4] Compactin and simvastatin, but not pravastatin, induce bone morphogenetic protein-2 in human osteosarcoma cells. Biochem Biophys Res Commun. 2000 May 19;271(3):688-92. doi: 10.1006/bbrc.2000.2697.
• [5] A cell-based reporter gene assay for determining induction of CYP3A4 in a high-volume system. J Pharmacol Exp Ther. 2002 Oct;303(1):412-23.
• [6] Asbestos induces nitric oxide synthesis in mesothelioma cells via Rho signaling inhibition. Am J Respir Cell Mol Biol. 2007 Jun;36(6):746-56. doi: 10.1165/rcmb.2006-0011OC. Epub 2007 Feb 22.
• [7] A randomized, double-blind trial comparing the efficacy and safety of pitavastatin versus pravastatin in patients with primary hypercholesterolemia. Atherosclerosis. 2002 Jun;162(2):373-9.
• [8] Equally potent inhibitors of cholesterol synthesis in human hepatocytes have distinguishable effects on different cytochrome P450 enzymes. Biopharm Drug Dispos. 2000 Dec;21(9):353-64.
• [9] Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
• [10] Cholesterol-lowering effect of NK-104, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, in guinea pig model of hyperlipidemia. Arzneimittelforschung. 2001;51(3):197-203.
• [11] New dimension of statin action on ApoB atherogenicity. Clin Cardiol. 2003 Jan;26(1 Suppl 1):I7-10.
• [12] Emerging drugs in peripheral arterial disease. Expert Opin Emerg Drugs. 2006 Mar;11(1):75-90.
• [13] Microarray and biochemical analysis of lovastatin-induced apoptosis of squamous cell carcinomas. Neoplasia. 2002 Jul-Aug;4(4):337-46.
• [14] The relative role of CYP3A4 and CYP3A5 in eplerenone metabolism. Toxicol Lett. 2019 Oct 15;315:9-13.
• [15] Characterization of the structural determinants required for potent mechanism-based inhibition of human cytochrome P450 1A1 by cannabidiol. Chem Biol Interact. 2014 May 25;215:62-8.
• [16] Retinoids activate the RXR/SXR-mediated pathway and induce the endogenous CYP3A4 activity in Huh7 human hepatoma cells. Toxicol Sci. 2006 Jul;92(1):51-60.
• [17] The novel azole R126638 is a selective inhibitor of ergosterol synthesis in Candida albicans, Trichophyton spp., and Microsporum canis. Antimicrob Agents Chemother. 2004 Sep;48(9):3272-8.
• [18] Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab Dispos. 2001 Jan;29(1):30-5.
• [19] Cetirizine and loratadine-based antihistamines with 5-lipoxygenase inhibitory activity. Bioorg Med Chem Lett. 2004 Nov 15;14(22):5591-4.
• [20] Mechanism-based inactivation of CYP3A by HIV protease inhibitors. J Pharmacol Exp Ther. 2005 Feb;312(2):583-91.
• [21] Studies of the toxicological potential of capsinoids, XIII: inhibitory effects of capsaicin and capsinoids on cytochrome P450 3A4 in human liver microsomes. Int J Toxicol. 2010 Mar;29(2 Suppl):22S-6S.
• [22] Investigation of the effects of axitinib on the pharmacokinetics of loperamide and its main metabolite N-demethylated loperamide in rats by UPLC-MS/MS. Chem Biol Interact. 2019 Sep 1;310:108744. doi: 10.1016/j.cbi.2019.108744. Epub 2019 Jul 9.
• [23] Peripheral blood expression profiles of bone morphogenetic proteins, tumor necrosis factor-superfamily molecules, and transcription factor Runx2 could be used as markers of the form of arthritis, disease activity, and therapeutic responsiveness. J Rheumatol. 2010 Feb;37(2):246-56. doi: 10.3899/jrheum.090167. Epub 2009 Dec 15.
• [24] Quercetin, a flavonoid, inhibits proliferation and increases osteogenic differentiation in human adipose stromal cells. Biochem Pharmacol. 2006 Nov 15;72(10):1268-78. doi: 10.1016/j.bcp.2006.08.021. Epub 2006 Sep 22.
• [25] Human oligodendrocytes derived from embryonic stem cells: Effect of noggin on phenotypic differentiation in vitro and on myelination in vivo. Mol Cell Neurosci. 2007 Mar;34(3):310-23. doi: 10.1016/j.mcn.2006.11.008. Epub 2006 Dec 28.
• [26] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [27] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [28] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [29] Simvastatin and atorvastatin enhance gene expression of collagen type 1 and osteocalcin in primary human osteoblasts and MG-63 cultures. J Cell Biochem. 2007 Aug 15;101(6):1430-8. doi: 10.1002/jcb.21259.
• [30] 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.
• [31] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [32] Cannabidiol and Oxygen-Ozone Combination Induce Cytotoxicity in Human Pancreatic Ductal Adenocarcinoma Cell Lines. Cancers (Basel). 2020 Sep 27;12(10):2774. doi: 10.3390/cancers12102774.
• [33] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [34] Cytoskeletal activation and altered gene expression in endothelial barrier regulation by simvastatin. Am J Respir Cell Mol Biol. 2004 May;30(5):662-70. doi: 10.1165/rcmb.2003-0267OC. Epub 2003 Nov 20.
• [35] Quercetin inhibits migration and invasion of SAS human oral cancer cells through inhibition of NF-B and matrix metalloproteinase-2/-9 signaling pathways. Anticancer Res. 2013 May;33(5):1941-50.
• [36] Retinoic acid and its 4-oxo metabolites are functionally active in human skin cells in vitro. J Invest Dermatol. 2005 Jul;125(1):143-53.
• [37] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [38] Combining prenylation inhibitors causes synergistic cytotoxicity, apoptosis and disruption of RAS-to-MAP kinase signalling in multiple myeloma cells. Br J Haematol. 2005 Sep;130(6):912-25. doi: 10.1111/j.1365-2141.2005.05696.x.
• [39] Pamidronate induced anti-proliferative, apoptotic, and anti-migratory effects in hepatocellular carcinoma. J Hepatol. 2006 Jan;44(1):142-50. doi: 10.1016/j.jhep.2005.09.022. Epub 2005 Nov 9.
• [40] RhoA GTPase inactivation by statins induces osteosarcoma cell apoptosis by inhibiting p42/p44-MAPKs-Bcl-2 signaling independently of BMP-2 and cell differentiation. Cell Death Differ. 2006 Nov;13(11):1845-56. doi: 10.1038/sj.cdd.4401873. Epub 2006 Feb 10.