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

General Information of Drug (ID: DMU9VDS)

• Drug Name: Mibefradil Drug Info
• Synonyms: Mibefradil (Cytostatic Checkpoint Therapy, ovarian cancer); Mibefradil (Cytostatic Checkpoint Therapy, ovarian cancer), Tau Therapeutics; Calcium T-channel inhibitor (Cytostatic Checkpoint Therapy, ovarian cancer), Tau Therapeutics

Indication

Disease Entry	ICD 11	Status	REF
Glioblastoma multiforme	2A00.0	Phase 1	[1]
Ovarian cancer	2C73	Withdrawn from market	[2] , [3]

• Cross-matching ID:
  PubChem CID: 60663
  ChEBI ID: CHEBI:6920
  CAS Number: CAS 116644-53-2
  TTD Drug ID: DMU9VDS
  VARIDT Drug ID: DR00781
  INTEDE Drug ID: DR1082

Molecule-Related Drug Atlas

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Solid tumour/cancer	2A00-2F9Z	Approved	[7]
Progesterone	DMUY35B	Premature labour	JB00	Approved	[8]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[9]
Estradiol	DMUNTE3	Breast cancer	2C60-2C65	Approved	[10]
Acetaminophen	DMUIE76	Pain	MG30-MG3Z	Approved	[11]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[12]
Etoposide	DMNH3PG	Solid tumour/cancer	2A00-2F9Z	Approved	[13]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[14]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[8]
Verapamil	DMA7PEW	Hypertension	BA00-BA04	Approved	[15]

Drug(s) Transported By P-glycoprotein 1 (ABCB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Bacterial infection	1A00-1C4Z	Approved	[5]
Doxorubicin	DMVP5YE	Solid tumour/cancer	2A00-2F9Z	Approved	[16]
Methotrexate	DM2TEOL	leukaemia	2A60-2B33	Approved	[17]
Folic acid	DMEMBJC	Folate-deficiency anemia	3A02.Y	Approved	[18]
Fluorouracil	DMUM7HZ	Solid tumour/cancer	2A00-2F9Z	Approved	[17]
Cisplatin	DMRHGI9	Solid tumour/cancer	2A00-2F9Z	Approved	[17]
Progesterone	DMUY35B	Premature labour	JB00	Approved	[19]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[17]
Estradiol	DMUNTE3	Breast cancer	2C60-2C65	Approved	[20]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[21]

Drug(s) Targeting Voltage-gated calcium channel alpha Cav3.2 (CACNA1H)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sodium bicarbonate	DMMU6BJ	Metabolic acidosis	5C73	Approved	[22]
Flunarizine	DMZU5JP	Migraine	8A80	Approved	[23]
ABT-639	DMEWQ4X	Pain	MG30-MG3Z	Phase 2	[24]
TTA-A8	DMWZCIF	Insomnia	7A00-7A0Z	Preclinical	[25]
U-92032	DMTYO3P	N. A.	N. A.	Terminated	[26]
ML218	DM3D21X	Discovery agent	N.A.	Investigative	[27]
KYS-05001	DM3MID9	Discovery agent	N.A.	Investigative	[28]
KYS-05077	DMHW40F	Discovery agent	N.A.	Investigative	[29]
KYS-05080	DM57BXZ	Discovery agent	N.A.	Investigative	[29]
Cis-N,5-dibenzyl-6-oxomorpholine-3-carboxamide	DM75SO4	Discovery agent	N.A.	Investigative	[30]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Voltage-gated calcium channel alpha Cav3.2 (CACNA1H)	TTZPWGN	CAC1H_HUMAN	Inhibitor	[4]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[5]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[6]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] 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: 2522).
• [3] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000236)
• [4] Mibefradil block of cloned T-type calcium channels. J Pharmacol Exp Ther. 2000 Oct;295(1):302-8.
• [5] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [6] Effect of mibefradil on CYP3A4 in vivo. J Clin Pharmacol. 2003 Oct;43(10):1091-100.
• [7] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
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• [9] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [10] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [11] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [12] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [13] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [14] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [15] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [16] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [17] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [18] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
• [19] Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
• [20] Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
• [21] Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
• [22] Acute renal failure. Clin Evid (Online). 2008 Sep 3;2008. pii: 2001.
• [23] Positive allosteric interaction of structurally diverse T-type calcium channel antagonists. Cell Biochem Biophys. 2009;55(2):81-93.
• [24] Effects of a T-type calcium channel blocker, ABT-639, on spontaneous activity in C-nociceptors in patients with painful diabetic neuropathy: a randomized controlled trial. Pain. 2015 Nov;156(11):2175-83.
• [25] Short-acting T-type calcium channel antagonists significantly modify sleep architecture in rodents. ACS Med Chem Lett. 2010 Aug 24;1(9):504-9.
• [26] Discovery of (2S)-1-(4-amino-2,3,5- trimethylphenoxy)-3-[4-[4-(4- fluorobenzyl)phenyl]-1-piperazinyl]-2-propanol dimethanesulfonate (SUN N8075): a ... J Med Chem. 2000 Sep 7;43(18):3372-6.
• [27] The Discovery and Characterization of ML218: A Novel, Centrally Active T-Type Calcium Channel Inhibitor with Robust Effects in STN Neurons and in a Rodent Model of Parkinson's Disease. ACS Chem Neurosci. 2011 Dec 21;2(12):730-742.
• [28] 3,4-Dihydroquinazoline derivatives as novel selective T-type Ca2+ channel blockers. Bioorg Med Chem Lett. 2004 Jul 5;14(13):3379-84.
• [29] Synthesis and biological evaluation of novel T-type calcium channel blockers. Bioorg Med Chem Lett. 2007 Jan 15;17(2):471-5.
• [30] Morpholin-2-one derivatives as novel selective T-type Ca2+ channel blockers. Bioorg Med Chem Lett. 2006 Oct 1;16(19):5244-8.