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Ovarian cancer	2C73	Withdrawn from market	[2], [3]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 2:
  Molecular Weight (mw); 495.6
  Topological Polar Surface Area (xlogp); 5.8
  Rotatable Bond Count (rotbonds); 12
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 6
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [4]
  Bioavailability: 75% of drug becomes completely available to its intended biological destination(s) [5]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 4 mL/min/kg [6]
  Half-life: The concentration or amount of drug in body reduced by one-half in 17 - 25 hours [6]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 2.8823 micromolar/kg/day [7]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.005% [6]
  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 [6]
• 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

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	[8]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[9]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[10]

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] BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
• [5] Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
• [6] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [7] 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
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