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Compound Detail

CHEMBL45816

MIBEFRADIL
💊 Approved Drug
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💊 Approved Drug
COCC(=O)O[C@]1(CCN(C)CCCc2nc3ccccc3[nH]2)CCc2cc(F)ccc2[C@@H]1C(C)C
ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID CHEMBL45816
Name MIBEFRADIL
Phase Approved
Structure Type MOL
InChI Key HBNPJJILLOYFJU-VMPREFPWSA-N
Therapeutic ✓ Yes

Known Names

Mibefradil Posicor 100 Posicor 50
32
Targets
106
Activities
3
Assay Types
9
PK Parameters
20
Publications
3
Known Names
3
Indications

Molecular Properties

495.6
MW (Da)
5.27
ALogP
5
HBA
1
HBD
67.5
PSA (Ų)
0.37
QED
1
Ro5 Violations
11
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1997
Availability Withdrawn
Chirality Single Enantiomer

Routes of Administration

Oral

Flags

Withdrawn
USAN Stem -dil
USAN Year 1994

Extended Properties

Molecular Formula C29H38FN3O3
MW 495.64
Aromatic Rings 3
Heavy Atoms 36
NP-Likeness -0.56

Indications

Cardiovascular Diseases Central Nervous System Neoplasms Glioblastoma

ATC Classification

C08CX01
mibefradil
Level 1: CARDIOVASCULAR SYSTEM
Level 2: CALCIUM CHANNEL BLOCKERS

Drug Warnings

Withdrawn
cardiotoxicity
potential to induce cardiac arrhythmias (including torsades de pointes) especially when taken concomitantly with other medications
Country: Worldwide   Year: 1998
Withdrawn
musculoskeletal toxicity
Safety concerns in relation to potential for serious drug interactions.; Reports of life-threatening interactions of the drug: extremely low heart rates and a risk of muscle injury; Following reports ...
Country: Worldwide   Year: 1998
Withdrawn
General Warning
Safety concerns in relation to potential for serious drug interactions.; Reports of life-threatening interactions of the drug: extremely low heart rates and a risk of muscle injury; Following reports ...
Country: Worldwide   Year: 1998
Withdrawn
musculoskeletal toxicity
reports of life- threatening interactions of the drug: extremely low heart rates and a risk of muscle injury
Country: Worldwide   Year: 1998
Withdrawn
cardiotoxicity
potential to induce cardiac arrhythmias (including torsades de pointes) especially when taken concomitantly with other medications
Country: Worldwide   Year: 1998
Withdrawn
General Warning
potential to induce cardiac arrhythmias (including torsades de pointes) especially when taken concomitantly with other medications
Country: Worldwide   Year: 1998
Withdrawn
cardiotoxicity
Safety concerns in relation to potential for serious drug interactions.; Reports of life-threatening interactions of the drug: extremely low heart rates and a risk of muscle injury; Following reports ...
Country: Worldwide   Year: 1998
Withdrawn
cardiotoxicity
reports of life- threatening interactions of the drug: extremely low heart rates and a risk of muscle injury
Country: Worldwide   Year: 1998

Activity Summary

IC50 101 meas. best 9.06
Ki 4 meas. best 6.72
EC50 1 meas. best 7.58

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Plasmodium yoelii yoelii
CHEMBL612328
 IC50 9.06 9.06 0.9 2
Unchecked
CHEMBL612545
 IC50 8.15 6.104 7.0 5
Heart
CHEMBL613629
 EC50 7.58 7.58 26.0 1
Voltage-dependent T-type calcium channel subunit alpha-1H
CHEMBL1859
 IC50 7.5 6.67 32.0 6
Cytochrome P450 2D6
CHEMBL289
 IC50 7.2 6.4733 63.0 3
Voltage-dependent T-type calcium channel subunit alpha-1G
CHEMBL4641
 IC50 7.19 6.0461 64.0 23
Voltage-dependent T-type calcium channel subunit alpha-1I
CHEMBL5558
 IC50 6.9 6.5967 126.0 3
Cytochrome P450 3A4
CHEMBL340
 IC50 6.89 6.47 130.0 4
Voltage-gated L-type calcium channel
CHEMBL2095229
 IC50 6.81 6.55 156.0 2
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
 Ki 6.72 6.585 190.0 2
Voltage-dependent L-type calcium channel subunit alpha-1C
CHEMBL1940
 IC50 6.7 6.65 202.0 2
Cytochrome P450 3A4
CHEMBL340
 Ki 6.55 6.095 280.0 2
Voltage-dependent N-type calcium channel subunit alpha-1B
CHEMBL4478
 IC50 6.38 6.125 416.0 2
Sodium channel protein type 4 subunit alpha
CHEMBL3509
 IC50 6.3 6.3 500.0 1
Sodium channel protein type 9 subunit alpha
CHEMBL4296
 IC50 6.3 6.3 500.0 1
Sodium channel protein type 5 subunit alpha
CHEMBL1980
 IC50 6.3 6.3 500.0 1
Sodium channel protein type 2 subunit alpha
CHEMBL3399
 IC50 6.3 6.3 500.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
 IC50 6.24 5.8606 580.0 17
Sodium channel alpha subunit
CHEMBL2331043
 IC50 6.01 6.01 980.0 1
Cacna1b/Cacnb3
CHEMBL4296086
 IC50 6.0 6.0 1000.0 1
Voltage-dependent L-type calcium channel subunit alpha-1C
CHEMBL3762
 IC50 5.96 5.96 1100.0 1
ATP-dependent translocase ABCB1
CHEMBL4302
 IC50 5.92 5.808 1200.0 5
Cytochrome P450 2C19
CHEMBL3622
 IC50 5.88 5.88 1320.0 1
Cytochrome P450 2J2
CHEMBL3491
 IC50 5.67 5.67 2140.0 1
Voltage-gated L-type calcium channel
CHEMBL2095177
 IC50 5.16 5.16 7000.0 1
ATP-dependent translocase ABCB1
CHEMBL2573
 IC50 5.13 5.13 7400.0 2
ATP-dependent translocase ABCB1
CHEMBL3467
 IC50 5.0 5.0 10000.0 2
NON-PROTEIN TARGET
CHEMBL3879801
 IC50 4.74 4.595 18400.0 2
SK-OV-3
CHEMBL614925
 IC50 4.69 4.69 20540.0 1
A2780
CHEMBL614004
 IC50 4.62 4.62 24230.0 1
A549
CHEMBL392
 IC50 4.61 4.57 24800.0 3
Bile salt export pump
CHEMBL6020
 IC50 4.6 4.6 25000.0 1
Cytochrome P450 2C9
CHEMBL3397
 IC50 4.55 4.55 28400.0 1
Calcium release-activated calcium channel protein 1
CHEMBL2384891
 IC50 4.28 4.28 52100.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 94.0 mL.min-1.kg-1 Rattus norvegicus
CL 36.0 mL.min-1.kg-1 Canis lupus familiaris
CL 7.0 mL.min-1.kg-1 Homo sapiens
CL 4.0 mL.min-1.kg-1 Homo sapiens
CL 56.5 mL.min-1.g-1 Homo sapiens
F 79.0 % Homo sapiens
Fu 0.005 - Homo sapiens
MRT 13.0 hr Homo sapiens
T1/2 13.0 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Plasmodium yoelii yoelii IC50 = 0.873 nM 9.06 Antimicrobial activity against Plasmodium yoelii 265 liver infected in mammalian... 18212104
Plasmodium yoelii yoelii IC50 = 0.873 nM 9.06 Antimalarial activity against liver stages of Plasmodium yoelii yoelii 22122518
Unchecked IC50 = 7.0 nM 8.15 Displacement of [3H]diltiazem from L-type calcium channel in rabbit muscle cells 18817368
Heart EC50 = 26.0 nM 7.58 Increase in coronary flow in Wistar rat Langendorff isolated perfused heart 26231163
Voltage-dependent T-type calcium channel subunit alpha-1H IC50 = 32.0 nM 7.5 Antagonist activity against T-type calcium channel subunit alpha-1H assessed as ... 20934333
Cytochrome P450 2D6 IC50 = 63.0 nM 7.2 Inhibition of human recombinant CYP2D6-mediated 7-methoxy-4(aminomethyl)-coumari... 23200256
Voltage-dependent T-type calcium channel subunit alpha-1G IC50 = 64.0 nM 7.19 Inhibition of Cav3.1 (unknown origin) 29116786
Voltage-dependent T-type calcium channel subunit alpha-1I IC50 = 126.0 nM 6.9 Inhibition of T-type calcium channel alpha1I by FLIPR 18817368
Cytochrome P450 3A4 IC50 = 130.0 nM 6.89 Inhibition of human cytochrome P450 3A4 12699389
Voltage-dependent T-type calcium channel subunit alpha-1H IC50 = 130.0 nM 6.89 Antagonist activity at human alpha1H T-type calcium channel expressed in HEK293 ... 18160281
Voltage-dependent T-type calcium channel subunit alpha-1H IC50 = 130.0 nM 6.89 Inhibition of Cav3.2 (unknown origin) 29116786
Voltage-dependent T-type calcium channel subunit alpha-1I IC50 = 130.0 nM 6.89 Inhibition of Cav3.3 (unknown origin) 29116786
Voltage-gated L-type calcium channel IC50 = 156.0 nM 6.81 Inhibition of voltage-gated L-type Ca channel (species unknown) 21300721
Voltage-dependent T-type calcium channel subunit alpha-1H IC50 = 181.0 nM 6.74 Inhibition of recombinant Cav3.2 channel (unknown origin) expressed in HEK293 ce... 26231163
Voltage-gated inwardly rectifying potassium channel KCNH2 Ki = 190.0 nM 6.72 Binding affinity at hERG expressed in HEK293 cells by fluorescence polarization ... 17536794
Voltage-dependent T-type calcium channel subunit alpha-1G IC50 = 200.0 nM 6.7 Inhibition of human Cav3.1 alpha1G expressed in HEK293 cells assessed as inhibit... 21875808
Voltage-dependent L-type calcium channel subunit alpha-1C IC50 = 202.0 nM 6.7 Inhibition of recombinant Cav1.2 channel (unknown origin) expressed in HEK293 ce... 26231163
Voltage-dependent L-type calcium channel subunit alpha-1C IC50 = 250.0 nM 6.6 Inhibition of Cav1.2 (unknown origin) 29116786
Cytochrome P450 3A4 Ki = 280.0 nM 6.55 Inhibition of recombinant CYP3A4 (unknown origin) expressed in baculosomes in pr... 21447734
Cytochrome P450 3A4 IC50 = 300.0 nM 6.52 Reversible inhibition of CYP3A4 22409598

Literature References

PubMed DOI Target Context # Activities
21447734 10.1124/dmd.111.038505 Cytochrome P450 3A4 19
12699389 10.1021/jm021012t ATP-dependent translocase ABCB1 13
27517811 10.1016/j.ejmech.2016.07.032 NON-PROTEIN TARGET 12
24529871 10.1016/j.bmcl.2014.01.071 A549 10
26739776 10.1016/j.bmcl.2015.12.010 A549 9
18426954 10.1124/dmd.108.020479 ADMET 4
22409598 10.1021/jm300065h Cytochrome P450 3A4 3
17150365 10.1016/j.bmc.2006.11.004 Voltage-dependent T-type calcium channel subunit alpha-1G 3
17536794 10.1021/jm0700565 Voltage-gated inwardly rectifying potassium channel KCNH2 3
17869104 10.1016/j.bmcl.2007.08.070 Voltage-dependent T-type calcium channel subunit alpha-1G 3
18817368 10.1021/jm800830n Canis familiaris 3
20621730 10.1016/j.bmcl.2010.05.030 Voltage-dependent T-type calcium channel subunit alpha-1G 3
10602692 10.1021/jm991030j Canis familiaris 2
20659804 10.1016/j.bmc.2010.06.082 Voltage-dependent T-type calcium channel subunit alpha-1G 2
10602692 10.1021/jm991030j Rattus norvegicus 2
15603940 10.1016/j.bmcl.2004.10.078 Voltage-dependent T-type calcium channel subunit alpha-1G 2
18817368 10.1021/jm800830n Unchecked 2
37468498 10.1038/s41467-023-40064-9 Muscarinic acetylcholine receptor M1 2
18625556 10.1016/j.bmcl.2008.06.037 Voltage-dependent T-type calcium channel subunit alpha-1G 2
10891117 10.1021/jm0000564 No relevant target 2

Data from ChEMBL 36 via Core Engine