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

General Information of Drug (ID: DMRWSGO)

• Drug Name: Bay K 8644 Drug Info
• Synonyms: 71145-03-4; methyl 2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylate; MLS000028858; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, methyl ester; C16H15F3N2O4; R(+)-BAY K 8644; SMR000058424; Methyl 2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-1,4-dihydropyridine-3-carboxylate

Indication

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

• Cross-matching ID:
  PubChem CID: 2303
  ChEBI ID: CHEBI:34555
  CAS Number: CAS 71145-03-4
  TTD Drug ID: DMRWSGO

Molecule-Related Drug Atlas

Drug(s) Targeting Voltage-gated L-type calcium channel (L-CaC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nifedipine	DMSVOZT	Angina pectoris	BA40	Approved	[5]
Clevidipine butyrate	DMW4M97	Hypertension	BA00-BA04	Approved	[6]
Epalrestat	DM5OGK0	Diabetic neuropathy	8C0Z	Approved	[7]
Otilonium bromide	DM05968	Gastric motility disorder	DA21	Approved	[8]
Levamlodipine	DM92S6N	Hypertension	BA00-BA04	Phase 4	[9]
Cilnidipine	DM1975O	High blood pressure	BA00	Phase 3	[10]
Pinaverium bromide	DM7OSHC	Irritable bowel syndrome	DD91.0	Phase 3	[8]
MEM-1003	DMYZU6G	Bipolar disorder	6A60	Phase 2a	[11]
Gallopamil	DMXBR27	Asthma	CA23	Phase 2	[12]
BAY-Y-5959	DMLO18H	Cardiovascular disease	BA00-BE2Z	Phase 2	[13]

Drug(s) Affected By Cytochrome P450 11B2, mitochondrial (CYP11B2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aldosterone	DM9S2JW	Hypertension	BA00-BA04	Approved	[14]
FADROZOLE	DM3C5GZ	Breast cancer	2C60-2C65	Approved	[15]
Erythromycin	DM4K7GQ	Acne vulgaris	ED80	Approved	[16]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[17]
Potassium Chloride	DMMTAJC	Hypokalemia	5C77	Approved	[18]
Dutasteride	DMQ4TJK	Benign prostatic hyperplasia	GA90	Approved	[19]
Mitotane	DMU1GX0	Adrenocortical carcinoma	2D11.Z	Approved	[20]
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[16]
Carbamazepine	DMZOLBI	Epilepsy	8A60-8A68	Approved	[21]
Irbesartan	DMTP1DC	Diabetic kidney disease	GB61.Z	Approved	[22]

Drug(s) Affected By Protein c-Fos (FOS)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[23]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[24]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[25]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[26]
Acebutolol	DM0TI4U	Hypertension	BA00-BA04	Approved	[25]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[27]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[28]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[29]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[30]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[31]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Voltage-gated L-type calcium channel (L-CaC)	TTXHYV6	NOUNIPROTAC	Activator	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cytochrome P450 11B2, mitochondrial (CYP11B2)	OTIOLWYN	C11B2_HUMAN	Gene/Protein Processing	[3]
Protein c-Fos (FOS)	OTJBUVWS	FOS_HUMAN	Gene/Protein Processing	[4]

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: 2511).
• [2] Molecular determinants of drug binding and action on L-type calcium channels. Annu Rev Pharmacol Toxicol. 1997;37:361-96.
• [3] Angiotensin II and potassium regulate human CYP11B2 transcription through common cis-elements. Mol Endocrinol. 1997 May;11(5):638-49.
• [4] The fibroblast growth factor receptors, FGFR-1 and FGFR-2, mediate two independent signalling pathways in human retinal pigment epithelial cells. Biochem Biophys Res Commun. 2005 Nov 11;337(1):241-7. doi: 10.1016/j.bbrc.2005.09.028.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [6] Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
• [7] Recent updates of N-type calcium channel blockers with therapeutic potential for neuropathic pain and stroke. Curr Top Med Chem. 2009;9(4):377-95.
• [8] Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313.
• [9] Effects of (S)-amlodipine and (R)-amlodipine on L-type calcium channel current of rat ventricular myocytes and cytosolic calcium of aortic smooth muscle cells. Pharmazie. 2008 Jun;63(6):470-4.
• [10] N- and L-type calcium channel antagonist improves glomerular dynamics, reverses severe nephrosclerosis, and inhibits apoptosis and proliferation in an l-NAME/SHR model. J Hypertens. 2002 May;20(5):993-1000.
• [11] Efficacy of MEM 1003, a novel calcium channel blocker, in delay and trace eyeblink conditioning in older rabbits. Neurobiol Aging. 2007 May;28(5):766-73.
• [12] Role of apoptosis in the kidney after reperfusion. Orv Hetil. 2008 Feb 17;149(7):305-15.
• [13] Hemodynamic effects of a calcium channel promoter, BAY y 5959, are preserved after chronic administration in ischemic heart failure in conscious dogs. J Pharmacol Exp Ther. 1998 Aug;286(2):760-6.
• [14] [Association study between a polymorphism of aldosterone synthetase gene and the pathogenesis of polycystic ovary syndrome]. Zhonghua Fu Chan Ke Za Zhi. 2003 Feb;38(2):94-7.
• [15] Synthesis and evaluation of (pyridylmethylene)tetrahydronaphthalenes/-indanes and structurally modified derivatives: potent and selective inhibitors of aldosterone synthase. J Med Chem. 2005 Mar 10;48(5):1563-75.
• [16] Modulation of steroidogenic gene expression and hormone production of H295R cells by pharmaceuticals and other environmentally active compounds. Toxicol Appl Pharmacol. 2007 Dec 1;225(2):142-53.
• [17] 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.
• [18] Blockade of T-type voltage-dependent Ca2+ channels by benidipine, a dihydropyridine calcium channel blocker, inhibits aldosterone production in human adrenocortical cell line NCI-H295R. Eur J Pharmacol. 2008 Apr 28;584(2-3):424-34. doi: 10.1016/j.ejphar.2008.02.001. Epub 2008 Feb 12.
• [19] Effects of dutasteride on the expression of genes related to androgen metabolism and related pathway in human prostate cancer cell lines. Invest New Drugs. 2007 Oct;25(5):491-7.
• [20] Mitotane alters mitochondrial respiratory chain activity by inducing cytochrome c oxidase defect in human adrenocortical cells. Endocr Relat Cancer. 2013 May 21;20(3):371-81.
• [21] Differential effects of antiepileptic drugs on steroidogenesis in a human in vitro cell model. Acta Neurol Scand Suppl. 2009;(189):14-21.
• [22] Aldosterone synthase (CYP11B2) -344 C/T polymorphism is related to antihypertensive response: result from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial. Am J Hypertens. 2002 May;15(5):389-93. doi: 10.1016/s0895-7061(02)02256-2.
• [23] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [24] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [25] Selection of drugs to test the specificity of the Tg.AC assay by screening for induction of the gadd153 promoter in vitro. Toxicol Sci. 2003 Aug;74(2):260-70. doi: 10.1093/toxsci/kfg113. Epub 2003 May 2.
• [26] Sertraline induces endoplasmic reticulum stress in hepatic cells. Toxicology. 2014 Aug 1;322:78-88. doi: 10.1016/j.tox.2014.05.007. Epub 2014 May 24.
• [27] Estrogen regulation in human breast cancer cells of new downstream gene targets involved in estrogen metabolism, cell proliferation and cell transformation. J Mol Endocrinol. 2004 Apr;32(2):397-414.
• [28] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [29] Methotrexate induces production of IL-1 and IL-6 in the monocytic cell line U937. Arthritis Res Ther. 2014 Jan 20;16(1):R17. doi: 10.1186/ar4444.
• [30] Simvastatin inhibits NOR-1 expression induced by hyperlipemia by interfering with CREB activation. Cardiovasc Res. 2005 Aug 1;67(2):333-41. doi: 10.1016/j.cardiores.2005.03.016. Epub 2005 Apr 21.
• [31] The G protein-coupled receptor GPR30 mediates c-fos up-regulation by 17beta-estradiol and phytoestrogens in breast cancer cells. J Biol Chem. 2004 Jun 25;279(26):27008-16. doi: 10.1074/jbc.M403588200. Epub 2004 Apr 16.