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Ovarian cancer	2C73	Withdrawn from market	[2]
------------------------------------------------------------------------------------

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
DrugBank ID: DB01388
TTD ID: D0W8XT
VARIDT ID: DR00781
INTEDE ID: DR1082

Combinatorial Drugs (CBD)

Click to Jump to the Detailed CBD Information of This Drug

Repurposed Drugs (RPD)

Click to Jump to the Detailed RPD Information of This Drug

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]

------------------------------------------------------------------------------------

Drug Transporter (DTP)

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

------------------------------------------------------------------------------------

Drug-Metabolizing Enzyme (DME)

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

------------------------------------------------------------------------------------

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]

------------------------------------------------------------------------------------

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.