Methoxy-acetic acid (1S,2S)-2-(2-{[3-(1H-benzoimidazol-2-yl)-propyl]-methyl-amino}-ethyl)-6-fluoro-1-isopropyl-1,2,3,4-tetrahydro-naphthalen-2-yl ester

ID: ALA45816

Chembl Id: CHEMBL45816

Cas Number: 116644-53-2

PubChem CID: 60663

Product Number: M128055

Max Phase: Approved

First Approval: 1997

Molecular Formula: C29H38FN3O3

Molecular Weight: 495.64

Molecule Type: Small molecule

Associated Items:

Names and Identifiers

Synonyms: Mibefradil | Posicor | Mibefradil|116644-53-2|Mibefradil [INN:BAN]|Ro 40-5967|Mibefradil (INN)|Mibefradil HCl|[(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|CHEMBL45816|CHEBI:6920|27B90X776A|Acetic acid, methoxy-, (1S,2S)-2-[2-[[3-(1H-benzimidazol-2-yl)propyl]methylamino]ethyl]-6-fluoro-1,2,3,4-tetrahydro-1-(1-methylethyl)-2-naphthalenyl ester|Mibefradil dihydrochloride hydrate|MIBEFRADIL [INN]|(1S,2S)-2-(2Show More

Synonyms from Alternative Forms(3): Mibefradil dihydrochloride | Mibefradil hydrochloride | RO 40-5967/001

Trade Names(2): Posicor 100 | Posicor 50

Canonical SMILES:  COCC(=O)O[C@]1(CCN(C)CCCc2nc3ccccc3[nH]2)CCc2cc(F)ccc2[C@@H]1C(C)C

Standard 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

Standard InChI Key:  HBNPJJILLOYFJU-VMPREFPWSA-N

Associated Targets(Human)

CACNA1H Tclin Voltage-gated T-type calcium channel alpha-1H subunit (1913 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CACNA1G Tclin Voltage-gated T-type calcium channel alpha-1G subunit (1361 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KCNH2 Tclin HERG (29587 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Homo sapiens (32628 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CYP3A4 Tclin Cytochrome P450 3A4 (53859 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ABCB1 Tchem P-glycoprotein 1 (14716 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CACNA1B Tclin Voltage-gated N-type calcium channel alpha-1B subunit (743 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SMPD1 Tchem Sphingomyelin phosphodiesterase (13561 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CACNA1I Tclin Voltage-gated T-type calcium channel alpha-1I subunit (425 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Caco-2 (12174 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
RAB9A Tbio Ras-related protein Rab-9A (22488 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
MTOR Tclin Serine/threonine-protein kinase mTOR (13850 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
MAPT Tclin Microtubule-associated protein tau (95507 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HIF1A Tchem Hypoxia-inducible factor 1 alpha (6027 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ALOX15 Tchem Arachidonate 15-lipoxygenase (7108 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
MAPK1 Tchem MAP kinase ERK2 (25055 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
NPC1 Tchem Niemann-Pick C1 protein (18985 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
THPO Tbio Thrombopoietin (834 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
TP53 Tchem Cellular tumor antigen p53 (48468 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CYP2D6 Tclin Cytochrome P450 2D6 (33882 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ATAD5 Tbio ATPase family AAA domain-containing protein 5 (122566 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
NFE2L2 Tchem Nuclear factor erythroid 2-related factor 2 (95332 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
DRD1 Tclin Dopamine D1 receptor (9720 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
EHMT2 Tchem Histone-lysine N-methyltransferase, H3 lysine-9 specific 3 (93046 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CBX1 Tbio Chromobox protein homolog 1 (92434 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ALOX15B Tchem Arachidonate 15-lipoxygenase, type II (7244 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CYP2C9 Tchem Cytochrome P450 2C9 (32119 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CYP2C19 Tchem Cytochrome P450 2C19 (29246 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CYP1A2 Tchem Cytochrome P450 1A2 (26471 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ATXN2 Tbio Ataxin-2 (54410 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
FEN1 Tchem Flap endonuclease 1 (12055 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HEK293 (82097 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SH-SY5Y (11521 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Liver microsomes (16955 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SNCA Tchem Alpha-synuclein (10960 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
A2780 (11979 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SK-OV-3 (52876 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ARSA Tbio Cerebroside-sulfatase (655 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
A549 (127892 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Liver microsome (8277 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SCN1A Tclin Sodium channel alpha subunit (30 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CACNA1C Tclin Voltage-gated L-type calcium channel (709 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CACNA1C Tclin Voltage-gated L-type calcium channel alpha-1C subunit (766 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CYP2J2 Tchem Cytochrome P450 2J2 (258 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ORAI1 Tchem Calcium release-activated calcium channel protein 1 (150 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ABCB11 Tchem Bile salt export pump (2311 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SCN5A Tclin Sodium channel protein type V alpha subunit (3462 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SCN9A Tclin Sodium channel protein type IX alpha subunit (8393 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HCT-116 (91556 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HDAC6 Tclin Histone deacetylase 6 (20808 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SLC6A3 Tclin Dopamine transporter (10535 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ESR1 Tclin Estrogen receptor alpha (17718 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ACHE Tclin Acetylcholinesterase (18204 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SLC6A2 Tclin Norepinephrine transporter (10102 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SLC6A4 Tclin Serotonin transporter (12625 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ADRA2A Tclin Alpha-2a adrenergic receptor (9450 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
OPRM1 Tclin Mu opioid receptor (19785 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
MAOA Tclin Monoamine oxidase A (11911 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HTR1A Tclin Serotonin 1a (5-HT1a) receptor (14969 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KDR Tclin Vascular endothelial growth factor receptor 2 (20924 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
PDE3A Tclin Phosphodiesterase 3A (3309 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
DRD3 Tclin Dopamine D3 receptor (14368 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CHRM2 Tclin Muscarinic acetylcholine receptor M2 (10671 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
F2 Tclin Thrombin (11687 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
TBXA2R Tclin Thromboxane A2 receptor (5717 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ADORA3 Tchem Adenosine A3 receptor (15931 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HRH3 Tclin Histamine H3 receptor (10389 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HTR2B Tclin Serotonin 2b (5-HT2b) receptor (10323 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ADORA1 Tclin Adenosine A1 receptor (17603 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
GABRA1 Tclin Gamma-aminobutyric acid receptor subunit alpha-1/alpha-2/beta-2/gamma-2 (1034 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
AR Tclin Androgen Receptor (11781 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
PGR Tclin Progesterone receptor (8562 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
PTGS1 Tclin Cyclooxygenase-1 (9233 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
PDE4A Tclin Phosphodiesterase 4A (1943 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ADRA1A Tclin Alpha-1a adrenergic receptor (8359 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CHRM1 Tclin Muscarinic acetylcholine receptor M1 (12690 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Associated Targets(non-human)

Rattus norvegicus (775804 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Canis familiaris (36305 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Abcb1a P-glycoprotein 3 (492 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Abcb1b P-glycoprotein 1 (174 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Cacna1c Voltage-gated L-type calcium channel (1164 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Plasmodium yoelii yoelii (73 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Saccharomyces cerevisiae (19171 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Rorc Nuclear receptor ROR-gamma (89407 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Chrm1 Muscarinic acetylcholine receptor M1 (3437 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Txnrd1 Thioredoxin reductase 1, cytoplasmic (45279 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Heart (1007 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Cacna1c Voltage-gated L-type calcium channel alpha-1C subunit (1321 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Trpv1 Vanilloid receptor (3290 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Trpm8 Transient receptor potential cation channel subfamily M member 8 (889 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Cacna1b Cacna1b/Cacnb3 (1 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Scn4a Sodium channel protein type IV alpha subunit (55 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Scn2a Sodium channel protein type II alpha subunit (191 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SARS-CoV-2 (38078 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
rep Replicase polyprotein 1ab (11336 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Gabra1 GABA receptor alpha-1 subunit (2848 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Molecule Features

Natural Product: YesOral: YesChemical Probe: NoParenteral: No
Molecule Type: Small moleculeTopical: NoFirst In Class: NoBlack Box: No
Chirality: YesAvailability: NoProdrug: No

Drug Indications

MESH IDMESH Heading EFO IDsEFO TermsMax Phase for IndicationReferences

Mechanisms of Action

Mechanism of ActionAction Typetarget IDTarget NameTarget TypeTarget OrganismBinding Site NameReferences

Calculated Properties

Molecular Weight: 495.64Molecular Weight (Monoisotopic): 495.2897AlogP: 5.27#Rotatable Bonds: 11
Polar Surface Area: 67.45Molecular Species: BASEHBA: 5HBD: 1
#RO5 Violations: 1HBA (Lipinski): 6HBD (Lipinski): 1#RO5 Violations (Lipinski): 1
CX Acidic pKa: 12.54CX Basic pKa: 9.82CX LogP: 5.16CX LogD: 2.75
Aromatic Rings: 3Heavy Atoms: 36QED Weighted: 0.37Np Likeness Score: -0.56

References

1. Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J..  (2003)  Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery.,  46  (9): [PMID:12699389] [10.1021/jm021012t]
2. Yoshida F, Topliss JG..  (2000)  QSAR model for drug human oral bioavailability.,  43  (13): [PMID:10891117] [10.1021/jm0000564]
3. Keserü GM..  (2003)  Prediction of hERG potassium channel affinity by traditional and hologram qSAR methods.,  13  (16): [PMID:12873512] [10.1016/s0960-894x(03)00492-x]
4. Lee YS, Lee BH, Park SJ, Kang SB, Rhim H, Park JY, Lee JH, Jeong SW, Lee JY..  (2004)  3,4-Dihydroquinazoline derivatives as novel selective T-type Ca2+ channel blockers.,  14  (13): [PMID:15177437] [10.1016/j.bmcl.2004.04.090]
5. Cavalli A, Poluzzi E, De Ponti F, Recanatini M..  (2002)  Toward a pharmacophore for drugs inducing the long QT syndrome: insights from a CoMFA study of HERG K(+) channel blockers.,  45  (18): [PMID:12190308] [10.1021/jm0208875]
6. Schneider G, Coassolo P, Lavé T..  (1999)  Combining in vitro and in vivo pharmacokinetic data for prediction of hepatic drug clearance in humans by artificial neural networks and multivariate statistical techniques.,  42  (25): [PMID:10602692] [10.1021/jm991030j]
7. Rajamani R, Tounge BA, Li J, Reynolds CH..  (2005)  A two-state homology model of the hERG K+ channel: application to ligand binding.,  15  (6): [PMID:15745831] [10.1016/j.bmcl.2005.01.008]
8. Rhim H, Lee YS, Park SJ, Chung BY, Lee JY..  (2005)  Synthesis and biological activity of 3,4-dihydroquinazolines for selective T-type Ca2+ channel blockers.,  15  (2): [PMID:15603940] [10.1016/j.bmcl.2004.10.078]
9. Du LP, Tsai KC, Li MY, You QD, Xia L..  (2004)  The pharmacophore hypotheses of I(Kr) potassium channel blockers: novel class III antiarrhythmic agents.,  14  (18): [PMID:15324906] [10.1016/j.bmcl.2004.06.070]
10. Tobita M, Nishikawa T, Nagashima R..  (2005)  A discriminant model constructed by the support vector machine method for HERG potassium channel inhibitors.,  15  (11): [PMID:15911273] [10.1016/j.bmcl.2005.03.080]
11. Ku IW, Cho S, Doddareddy MR, Jang MS, Keum G, Lee JH, Chung BY, Kim Y, Rhim H, Kang SB..  (2006)  Morpholin-2-one derivatives as novel selective T-type Ca2+ channel blockers.,  16  (19): [PMID:16876404] [10.1016/j.bmcl.2006.05.031]
12. Jo MN, Seo HJ, Kim Y, Seo SH, Rhim H, Cho YS, Cha JH, Koh HY, Choo H, Pae AN..  (2007)  Novel T-type calcium channel blockers: dioxoquinazoline carboxamide derivatives.,  15  (1): [PMID:17035033] [10.1016/j.bmc.2006.09.051]
13. Doddareddy MR, Choo H, Cho YS, Rhim H, Koh HY, Lee JH, Jeong SW, Pae AN..  (2007)  3D pharmacophore based virtual screening of T-type calcium channel blockers.,  15  (2): [PMID:17074493] [10.1016/j.bmc.2006.10.013]
14. Park JH, Choi JK, Lee E, Lee JK, Rhim H, Seo SH, Kim Y, Doddareddy MR, Pae AN, Kang J, Roh EJ..  (2007)  Lead discovery and optimization of T-type calcium channel blockers.,  15  (3): [PMID:17150365] [10.1016/j.bmc.2006.11.004]
15. Singleton DH, Boyd H, Steidl-Nichols JV, Deacon M, Groot MJ, Price D, Nettleton DO, Wallace NK, Troutman MD, Williams C, Boyd JG..  (2007)  Fluorescently labeled analogues of dofetilide as high-affinity fluorescence polarization ligands for the human ether-a-go-go-related gene (hERG) channel.,  50  (13): [PMID:17536794] [10.1021/jm0700565]
16. Seo HN, Choi JY, Choe YJ, Kim Y, Rhim H, Lee SH, Kim J, Joo DJ, Lee JY..  (2007)  Discovery of potent T-type calcium channel blocker.,  17  (21): [PMID:17869104] [10.1016/j.bmcl.2007.08.070]
17. Choi JY, Seo HN, Lee MJ, Park SJ, Park SJ, Jeon JY, Kang JH, Pae AN, Rhim H, Lee JY..  (2007)  Synthesis and biological evaluation of novel T-type calcium channel blockers.,  17  (2): [PMID:17064894] [10.1016/j.bmcl.2006.10.024]
18. Kim HS, Kim Y, Doddareddy MR, Seo SH, Rhim H, Tae J, Pae AN, Choo H, Cho YS..  (2007)  Design, synthesis, and biological evaluation of 1,3-dioxoisoindoline-5-carboxamide derivatives as T-type calcium channel blockers.,  17  (2): [PMID:17092715] [10.1016/j.bmcl.2006.10.042]
19. Kornhuber J, Tripal P, Reichel M, Terfloth L, Bleich S, Wiltfang J, Gulbins E..  (2008)  Identification of new functional inhibitors of acid sphingomyelinase using a structure-property-activity relation model.,  51  (2): [PMID:18027916] [10.1021/jm070524a]
20. Hangeland JJ, Cheney DL, Friends TJ, Swartz S, Levesque PC, Rich AJ, Sun L, Bridal TR, Adam LP, Normandin DE, Murugesan N, Ewing WR..  (2008)  Design and SAR of selective T-type calcium channel antagonists containing a biaryl sulfonamide core.,  18  (2): [PMID:18160281] [10.1016/j.bmcl.2007.11.103]
21. Yang ZQ, Barrow JC, Shipe WD, Schlegel KA, Shu Y, Yang FV, Lindsley CW, Rittle KE, Bock MG, Hartman GD, Uebele VN, Nuss CE, Fox SV, Kraus RL, Doran SM, Connolly TM, Tang C, Ballard JE, Kuo Y, Adarayan ED, Prueksaritanont T, Zrada MM, Marino MJ, Graufelds VK, DiLella AG, Reynolds IJ, Vargas HM, Bunting PB, Woltmann RF, Magee MM, Koblan KS, Renger JJ..  (2008)  Discovery of 1,4-substituted piperidines as potent and selective inhibitors of T-type calcium channels.,  51  (20): [PMID:18817368] [10.1021/jm800830n]
22. Jia L, Sun H..  (2008)  Support vector machines classification of hERG liabilities based on atom types.,  16  (11): [PMID:18448342] [10.1016/j.bmc.2008.04.028]
23. Lee HK, Lee YS, Roh EJ, Rhim H, Lee JY, Shin KJ..  (2008)  Synthesis and evaluation of alpha,alpha'-disubstituted phenylacetate derivatives for T-type calcium channel blockers.,  18  (15): [PMID:18625556] [10.1016/j.bmcl.2008.06.037]
24. Ermondi G, Visentin S, Caron G..  (2009)  GRIND-based 3D-QSAR and CoMFA to investigate topics dominated by hydrophobic interactions: the case of hERG K+ channel blockers.,  44  (5): [PMID:19110341] [10.1016/j.ejmech.2008.11.009]
25. Du-Cuny L, Song Z, Moses S, Powis G, Mash EA, Meuillet EJ, Zhang S..  (2009)  Computational modeling of novel inhibitors targeting the Akt pleckstrin homology domain.,  17  (19): [PMID:19734051] [10.1016/j.bmc.2009.08.022]
26. Guerra A, Campillo NE, Páez JA..  (2010)  Neural computational prediction of oral drug absorption based on CODES 2D descriptors.,  45  (3): [PMID:20022146] [10.1016/j.ejmech.2009.11.034]
27. Gu SJ, Lee JK, Pae AN, Chung HJ, Rhim H, Han SY, Min SJ, Cho YS..  (2010)  Synthesis and biological evaluation of 1,4-diazepane derivatives as T-type calcium channel blockers.,  20  (9): [PMID:20382529] [10.1016/j.bmcl.2010.03.084]
28. Lee JE, Koh HY, Seo SH, Baek YY, Rhim H, Cho YS, Choo H, Pae AN..  (2010)  Synthesis and biological evaluation of oxazole derivatives as T-type calcium channel blockers.,  20  (14): [PMID:20621730] [10.1016/j.bmcl.2010.05.030]
29. Kam YL, Rhee HK, Rhim H, Back SK, Na HS, Choo HY..  (2010)  Synthesis and T-type calcium channel blocking activity of novel diphenylpiperazine compounds, and evaluation of in vivo analgesic activity.,  18  (16): [PMID:20659804] [10.1016/j.bmc.2010.06.082]
30. Mahmoudi N, Garcia-Domenech R, Galvez J, Farhati K, Franetich JF, Sauerwein R, Hannoun L, Derouin F, Danis M, Mazier D..  (2008)  New active drugs against liver stages of Plasmodium predicted by molecular topology.,  52  (4): [PMID:18212104] [10.1128/aac.01043-07]
31. Fritch PC, Krajewski J..  (2010)  Design, syntheses, and SAR of 2,8-diazaspiro[4.5]decanones as T-type calcium channel antagonists.,  20  (22): [PMID:20934333] [10.1016/j.bmcl.2010.09.098]
32. PubChem BioAssay data set, 
33. PubChem BioAssay data set, 
34. PubChem BioAssay data set, 
35. Obach RS, Lombardo F, Waters NJ..  (2008)  Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.,  36  (7): [PMID:18426954] [10.1124/dmd.108.020479]
36. Choi YH, Baek du J, Seo SH, Lee JK, Pae AN, Cho YS, Min SJ..  (2011)  Facile synthesis and biological evaluation of 3,3-diphenylpropanoyl piperazines as T-type calcium channel blockers.,  21  (1): [PMID:21126876] [10.1016/j.bmcl.2010.11.033]
37. Talevi A, Goodarzi M, Ortiz EV, Duchowicz PR, Bellera CL, Pesce G, Castro EA, Bruno-Blanch LE..  (2011)  Prediction of drug intestinal absorption by new linear and non-linear QSPR.,  46  (1): [PMID:21112128] [10.1016/j.ejmech.2010.11.005]
38. Greene N, Fisk L, Naven RT, Note RR, Patel ML, Pelletier DJ..  (2010)  Developing structure-activity relationships for the prediction of hepatotoxicity.,  23  (7): [PMID:20553011] [10.1021/tx1000865]
39. Ekins S, Williams AJ, Xu JJ..  (2010)  A predictive ligand-based Bayesian model for human drug-induced liver injury.,  38  (12): [PMID:20843939] [10.1124/dmd.110.035113]
40.  (2008)  Casarett and Doull's Toxicology The Basic Science of Poisons, 7th edition, 
41. Fontana E, Dansette PM, Poli SM..  (2005)  Cytochrome p450 enzymes mechanism based inhibitors: common sub-structures and reactivity.,  (1): [PMID:16248836] [10.2174/138920005774330639]
42. Gozalbes R, Jacewicz M, Annand R, Tsaioun K, Pineda-Lucena A..  (2011)  QSAR-based permeability model for drug-like compounds.,  19  (8): [PMID:21458999] [10.1016/j.bmc.2011.03.011]
43. Watanuki S, Matsuura K, Tomura Y, Okada M, Okazaki T, Ohta M, Tsukamoto S..  (2011)  Synthesis and pharmacological evaluation of 1-alkyl-N-[2-ethyl-2-(4-fluorophenyl)butyl]piperidine-4-carboxamide derivatives as novel antihypertensive agents.,  19  (18): [PMID:21875808] [10.1016/j.bmc.2011.07.030]
44. Woo HM, Lee YS, Roh EJ, Seo SH, Song CM, Chung HJ, Pae AN, Shin KJ..  (2011)  Synthesis and biological evaluation of 4-piperidinecarboxylate and 4-piperidinecyanide derivatives for T-type calcium channel blockers.,  21  (19): [PMID:21843937] [10.1016/j.bmcl.2011.07.087]
45. PubChem BioAssay data set, 
46. Liu Z, Shi Q, Ding D, Kelly R, Fang H, Tong W..  (2011)  Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).,  (12): [PMID:22194678] [10.1371/journal.pcbi.1002310]
47. Nagy H, Goda K, Fenyvesi F, Bacsó Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabó G..  (2004)  Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies.,  315  (1): [PMID:14985103] [10.1016/j.bbrc.2004.01.156]
48. Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J..  (2003)  Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery.,  46  (9): [PMID:12699389] [10.1021/jm021012t]
49. Ekins S, Kim RB, Leake BF, Dantzig AH, Schuetz EG, Lan LB, Yasuda K, Shepard RL, Winter MA, Schuetz JD, Wikel JH, Wrighton SA..  (2002)  Three-dimensional quantitative structure-activity relationships of inhibitors of P-glycoprotein.,  61  (1): [PMID:11961113] [10.1124/mol.61.5.964]
50. Wandel C, Kim RB, Guengerich FP, Wood AJ..  (2000)  Mibefradil is a P-glycoprotein substrate and a potent inhibitor of both P-glycoprotein and CYP3A in vitro.,  28  (1): [PMID:10901697]
51. Rodrigues T, Prudêncio M, Moreira R, Mota MM, Lopes F..  (2012)  Targeting the liver stage of malaria parasites: a yet unmet goal.,  55  (3): [PMID:22122518] [10.1021/jm201095h]
52. Orr ST, Ripp SL, Ballard TE, Henderson JL, Scott DO, Obach RS, Sun H, Kalgutkar AS..  (2012)  Mechanism-based inactivation (MBI) of cytochrome P450 enzymes: structure-activity relationships and discovery strategies to mitigate drug-drug interaction risks.,  55  (11): [PMID:22409598] [10.1021/jm300065h]
53. Park JE, Ji WK, Jang JW, Pae AN, Choi K, Choi KH, Kang J, Roh EJ..  (2013)  Synthesis and biological evaluation of 1-(2-hydroxy-3-phenyloxypropyl)piperazine derivatives as T-type calcium channel blockers.,  23  (6): [PMID:23395659] [10.1016/j.bmcl.2012.12.072]
54. Giordanetto F, Wållberg A, Knerr L, Selmi N, Ullah V, Thorstensson F, Lindelöf Å, Karlsson S, Nikitidis G, Llinas A, Wang QD, Lindqvist A, Högberg G, Lindhardt E, Åstrand A, Duker G..  (2013)  Discovery of N-[[1-[2-(tert-butylcarbamoylamino)ethyl]-4-(hydroxymethyl)-4-piperidyl]methyl]-3,5-dichloro-benzamide as a selective T-type calcium channel (Cav3.2) inhibitor.,  23  (1): [PMID:23200256] [10.1016/j.bmcl.2012.10.140]
55. Jang SJ, Choi HW, Choi DL, Cho S, Rim HK, Choi HE, Kim KS, Huang M, Rhim H, Lee KT, Lee JY..  (2013)  In vitro cytotoxicity on human ovarian cancer cells by T-type calcium channel blockers.,  23  (24): [PMID:24220170] [10.1016/j.bmcl.2013.10.049]
56. Choi DL, Jang SJ, Cho S, Choi HE, Rim HK, Lee KT, Lee JY..  (2014)  Inhibition of cellular proliferation and induction of apoptosis in human lung adenocarcinoma A549 cells by T-type calcium channel antagonist.,  24  (6): [PMID:24529871] [10.1016/j.bmcl.2014.01.071]
57. Han M, Song C, Jeong N, Hahn HG..  (2014)  Exploration of 3-Aminoazetidines as Triple Reuptake Inhibitors by Bioisosteric Modification of 3-α-Oxyazetidine.,  (9): [PMID:25221656] [10.1021/ml500187a]
58. Yun J, Han M, Song C, Cheon SH, Choi K, Hahn HG..  (2014)  Synthesis and biological evaluation of 3-phenethylazetidine derivatives as triple reuptake inhibitors.,  24  (15): [PMID:24974340] [10.1016/j.bmcl.2014.06.026]
59. Mirams GR, Cui Y, Sher A, Fink M, Cooper J, Heath BM, McMahon NC, Gavaghan DJ, Noble D..  (2011)  Simulation of multiple ion channel block provides improved early prediction of compounds' clinical torsadogenic risk.,  91  [PMID:21300721] [10.1093/cvr/cvr044]
60. Wiśniowska B, Mendyk A, Fijorek K, Glinka A, Polak S..  (2012)  Predictive model for L-type channel inhibition: multichannel block in QT prolongation risk assessment.,  32  [PMID:22761000] [10.1002/jat.2784]
61. Kramer J, Obejero-Paz CA, Myatt G, Kuryshev YA, Bruening-Wright A, Verducci JS, Brown AM..  (2013)  MICE models: superior to the HERG model in predicting Torsade de Pointes.,  [PMID:23812503] [10.1038/srep02100]
62. Foti RS, Rock DA, Pearson JT, Wahlstrom JL, Wienkers LC..  (2011)  Mechanism-based inactivation of cytochrome P450 3A4 by mibefradil through heme destruction.,  39  (7): [PMID:21447734] [10.1124/dmd.111.038505]
63. Ren S, Zeng J, Mei Y, Zhang JZ, Yan SF, Fei J, Chen L..  (2013)  Discovery and characterization of novel, potent, and selective cytochrome P450 2J2 inhibitors.,  41  (1): [PMID:23033255] [10.1124/dmd.112.048264]
64. Farrell TL, Poquet L, Dew TP, Barber S, Williamson G..  (2012)  Predicting phenolic acid absorption in Caco-2 cells: a theoretical permeability model and mechanistic study.,  40  (2): [PMID:22096083] [10.1124/dmd.111.041665]
65. Renneberg D, Hubler F, Rey M, Hess P, Delahaye S, Gatfield J, Iglarz M, Hilpert K..  (2015)  Discovery of novel bridged tetrahydronaphthalene derivatives as potent T/L-type calcium channel blockers.,  25  (18): [PMID:26231163] [10.1016/j.bmcl.2015.07.038]
66. IC50 data for the L-type calcium channel extracted from a set of literature articles, 
67. WHO Anatomical Therapeutic Chemical Classification, 
68. British National Formulary (72nd edition), 
69. Azimi I, Flanagan JU, Stevenson RJ, Inserra M, Vetter I, Monteith GR, Denny WA..  (2017)  Evaluation of known and novel inhibitors of Orai1-mediated store operated Ca2+ entry in MDA-MB-231 breast cancer cells using a Fluorescence Imaging Plate Reader assay.,  25  (1): [PMID:27856238] [10.1016/j.bmc.2016.11.007]
70. Kim JH, Keum G, Chung H, Nam G..  (2016)  Synthesis and T-type calcium channel-blocking effects of aryl(1,5-disubstituted-pyrazol-3-yl)methyl sulfonamides for neuropathic pain treatment.,  123  [PMID:27517811] [10.1016/j.ejmech.2016.07.032]
71. Morgan RE, Trauner M, van Staden CJ, Lee PH, Ramachandran B, Eschenberg M, Afshari CA, Qualls CW, Lightfoot-Dunn R, Hamadeh HK..  (2010)  Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development.,  118  (2): [PMID:20829430] [10.1093/toxsci/kfq269]
72. Capuzzi SJ, Sun W, Muratov EN, Martínez-Romero C, He S, Zhu W, Li H, Tawa G, Fisher EG, Xu M, Shinn P, Qiu X, García-Sastre A, Zheng W, Tropsha A..  (2018)  Computer-Aided Discovery and Characterization of Novel Ebola Virus Inhibitors.,  61  (8): [PMID:29624387] [10.1021/acs.jmedchem.8b00035]
73. Bezençon O, Heidmann B, Siegrist R, Stamm S, Richard S, Pozzi D, Corminboeuf O, Roch C, Kessler M, Ertel EA, Reymond I, Pfeifer T, de Kanter R, Toeroek-Schafroth M, Moccia LG, Mawet J, Moon R, Rey M, Capeleto B, Fournier E..  (2017)  Discovery of a Potent, Selective T-type Calcium Channel Blocker as a Drug Candidate for the Treatment of Generalized Epilepsies.,  60  (23): [PMID:29116786] [10.1021/acs.jmedchem.7b01236]
74. Du Nguyen H, Okada T, Kitamura S, Yamaoka S, Horaguchi Y, Kasanami Y, Sekiguchi F, Tsubota M, Yoshida S, Nishikawa H, Kawabata A, Toyooka N..  (2018)  Design and synthesis of novel anti-hyperalgesic agents based on 6-prenylnaringenin as the T-type calcium channel blockers.,  26  (15): [PMID:30031654] [10.1016/j.bmc.2018.07.023]
75. Unpublished dataset, 
76. Franck Touret, Magali Gilles, Karine Barral, Antoine Nougairède, Etienne Decroly, Xavier de Lamballerie, Bruno Coutard.  (2020)  In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication,  [10.1101/2020.04.03.023846]
77. Son WS, Jeong KS, Lim SM, Pae AN..  (2019)  Structural hybridization of pyrrolidine-based T-type calcium channel inhibitors and exploration of their analgesic effects in a neuropathic pain model.,  29  (10): [PMID:30928197] [10.1016/j.bmcl.2019.03.026]
78. Kim JH, Nam G..  (2016)  Synthesis and evaluation of 6-pyrazoylamido-3N-substituted azabicyclo[3,1,0]hexane derivatives as T-type calcium channel inhibitors for treatment of neuropathic pain.,  24  (21): [PMID:27591007] [10.1016/j.bmc.2016.06.006]
79. Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani.  (2020)  Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen,  [10.6019/CHEMBL4495564]
80. Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen , Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon and Pieter Leyssen.  (2020)  Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort,  [10.6019/CHEMBL4495565]
81. Nam Y, Ryu KD, Jang C, Moon YH, Kim M, Ko D, Chung KS, Gandini MA, Lee KT, Zamponi GW, Lee JY..  (2020)  Synthesis and cytotoxic effects of 2-thio-3,4-dihydroquinazoline derivatives as novel T-type calcium channel blockers.,  28  (11): [PMID:32327350] [10.1016/j.bmc.2020.115491]
82. Byun JS,Sohn JM,Leem DG,Park B,Nam JH,Shin DH,Shin JS,Kim HJ,Lee KT,Lee JY.  (2016)  In vitro synergistic anticancer activity of the combination of T-type calcium channel blocker and chemotherapeutic agent in A549 cells.,  26  (3.0): [PMID:26739776] [10.1016/j.bmcl.2015.12.010]
83. Bernhard Ellinger, Justus Dick, Vanessa Lage-Rupprecht, Bruce Schultz, Andrea Zaliani, Marcin Namysl, Stephan Gebel, Ole Pless, Jeanette Reinshagen, Christian Ebeling, Alexander Esser, Marc Jacobs, Carsten Claussen, and Martin Hofmann-Apitius.  (2021)  HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators,  [10.6019/CHEMBL4808148]
84. Unpublished dataset, 
85. Sutherland JJ, Yonchev D, Fekete A, Urban L..  (2023)  A preclinical secondary pharmacology resource illuminates target-adverse drug reaction associations of marketed drugs.,  14  (1): [PMID:37468498] [10.1038/s41467-023-40064-9]