Details of the Drug

General Information of Drug (ID: DMU9VDS)

Drug Name

Mibefradil

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Ovarian cancer	2C73	Withdrawn from market	[2]
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Affected Organisms

Humans and other mammals

ATC Code

C08CX01: Mibefradil

C08CX: Other selective calcium channel blockers with mainly vascular effects

C08C: SELECTIVE CALCIUM CHANNEL BLOCKERS WITH MAINLY VASCULAR EFFECTS

C08: CALCIUM CHANNEL BLOCKERS

C: CARDIOVASCULAR SYSTEM

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 2

Molecular Weight (mw)

495.6

Logarithm of the Partition Coefficient (xlogp)

5.8

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [3]
Bioavailability: 75% of drug becomes completely available to its intended biological destination(s) [4]
Clearance: The drug present in the plasma can be removed from the body at the rate of 4 mL/min/kg [5]
Half-life: The concentration or amount of drug in body reduced by one-half in 17 - 25 hours [5]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 2.8823 micromolar/kg/day [6]
Unbound Fraction: The unbound fraction of drug in plasma is 0.005% [5]
Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 3.1 L/kg [5]

Chemical Identifiers

Formula: C29H38FN3O3
IUPAC Name: [(1S,2S)-2-[2-[3-(1H-benzimidazol-2-yl)propyl-methylamino]ethyl]-6-fluoro-1-propan-2-yl-3,4-dihydro-1H-naphthalen-2-yl] 2-methoxyacetate
Canonical SMILES: CC(C)[C@H]1C2=C(CC[C@@]1(CCN(C)CCCC3=NC4=CC=CC=C4N3)OC(=O)COC)C=C(C=C2)F
InChI: InChI=1S/C29H38FN3O3/c1-20(2)28-23-12-11-22(30)18-21(23)13-14-29(28,36-27(34)19-35-4)15-17-33(3)16-7-10-26-31-24-8-5-6-9-25(24)32-26/h5-6,8-9,11-12,18,20,28H,7,10,13-17,19H2,1-4H3,(H,31,32)/t28-,29-/m0/s1
InChIKey: HBNPJJILLOYFJU-VMPREFPWSA-N

Cross-matching ID

PubChem CID: 60663
ChEBI ID: CHEBI:6920
CAS Number: 116644-53-2
UNII: 27B90X776A
DrugBank ID: DB01388
TTD ID: D0W8XT
VARIDT ID: DR00781
INTEDE ID: DR1082

Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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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	[7]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[8]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)_{Main DME}	DE4LYSA	CP3A4_HUMAN	Substrate	[9]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Gene/Protein Processing	[10]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Gene/Protein Processing	[11]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Gene/Protein Processing	[12]
Voltage-dependent T-type calcium channel subunit alpha-1G (CACNA1G)	OTGKBRE4	CAC1G_HUMAN	Drug Response	[13]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

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	BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
4	Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
5	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
6	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
7	Mibefradil block of cloned T-type calcium channels. J Pharmacol Exp Ther. 2000 Oct;295(1):302-8.
8	Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
9	Effect of mibefradil on CYP3A4 in vivo. J Clin Pharmacol. 2003 Oct;43(10):1091-100.
10	Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci. 2010 Dec; 118(2):485-500.
11	Automated screening with confirmation of mechanism-based inactivation of CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP1A2 in pooled human liver microsomes. Drug Metab Dispos. 2005 Aug;33(8):1211-9.
12	Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.
13	The Ca(2+) channel antagonists mibefradil and pimozide inhibit cell growth via different cytotoxic mechanisms. Mol Pharmacol. 2002 Aug;62(2):210-9. doi: 10.1124/mol.62.2.210.