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Compound Detail

CHEMBL1484

NICARDIPINE
💊 Approved Drug
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💊 Approved Drug
COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)Cc2ccccc2)C1c1cccc([N+](=O)[O-])c1

Basic Information

ChEMBL ID CHEMBL1484
Name NICARDIPINE
Phase Approved
Structure Type MOL
InChI Key ZBBHBTPTTSWHBA-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

Nicardipine Nicardipine (stn) Nicardipino Perpidine
35
Targets
67
Activities
3
Assay Types
30
PK Parameters
20
Publications
4
Known Names
9
Indications

Molecular Properties

479.5
MW (Da)
3.68
ALogP
8
HBA
1
HBD
111.0
PSA (Ų)
0.33
QED
0
Ro5 Violations
9
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1988
Availability Prescription
Chirality Racemic

Routes of Administration

Oral Parenteral

Flags

Natural Product
USAN Stem -dipine; -pine
USAN Year 1979

Extended Properties

Molecular Formula C26H29N3O6
MW 479.53
Aromatic Rings 2
Heavy Atoms 35
NP-Likeness -1.11

Indications

Cardiovascular Diseases Hypertension Muscle Cramp Pre-Eclampsia Aortic Aneurysm, Thoracic Stroke Subarachnoid Hemorrhage Brain Neoplasms Coronary Disease

ATC Classification

C08CA04
nicardipine
Level 1: CARDIOVASCULAR SYSTEM
Level 2: CALCIUM CHANNEL BLOCKERS

Activity Summary

IC50 58 meas. best 10.59
Ki 7 meas. best 9.08
EC50 2 meas. best 6.3

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Rattus norvegicus
CHEMBL376
IC50 10.59 8.22 0.0 2
Sus scrofa
CHEMBL613488
IC50 9.52 9.52 0.3 1
Voltage-gated L-type calcium channel
CHEMBL2095177
Ki 9.08 9.08 0.8 1
Voltage-gated L-type calcium channel
CHEMBL2095177
IC50 8.57 8.57 2.7 1
Voltage-dependent L-type calcium channel subunit alpha-1C
CHEMBL1940
IC50 6.6 5.4133 250.0 3
Cytochrome P450 2C9
CHEMBL3397
Ki 6.55 6.55 280.0 1
Cytochrome P450 3A4
CHEMBL340
IC50 6.42 6.4 380.0 2
Cytochrome P450 2C9
CHEMBL3397
IC50 6.42 6.3 378.0 2
Transient receptor potential cation channel subfamily A member 1
CHEMBL1075310
EC50 6.3 6.3 500.0 1
Cytochrome P450 2C19
CHEMBL3622
IC50 6.25 5.865 560.0 2
ATP-dependent translocase ABCB1
CHEMBL4302
IC50 6.02 5.2986 950.0 14
Adrenergic receptor alpha-2
CHEMBL2093864
IC50 5.85 5.85 1400.0 1
Cytochrome P450 2C8
CHEMBL3721
IC50 5.81 5.81 1560.0 1
Cytochrome P450 2D6
CHEMBL289
IC50 5.8 5.775 1590.0 2
Cytochrome P450 2J2
CHEMBL3491
IC50 5.77 5.77 1690.0 1
ATP-dependent translocase ABCB1
CHEMBL2573
IC50 5.6 5.6 2500.0 2
Adenosine receptor A3
CHEMBL256
Ki 5.49 5.49 3250.0 1
Adrenergic receptor alpha-1
CHEMBL1907610
IC50 5.44 5.44 3600.0 1
Unchecked
CHEMBL612545
EC50 5.33 5.33 4700.0 1
Broad substrate specificity ATP-binding cassette transporter ABCG2
CHEMBL5393
IC50 5.32 5.05 4800.0 2
Equilibrative nucleoside transporter 1
CHEMBL4604
Ki 5.27 5.27 5360.0 1
Bile salt export pump
CHEMBL6020
IC50 5.1 5.1 7870.0 4
ATP-dependent translocase ABCB1
CHEMBL3467
IC50 5.1 5.1 8000.0 2
Trypanosoma cruzi
CHEMBL368
IC50 4.97 4.97 10590.0 1
Adenosine receptor A3
CHEMBL3360
Ki 4.96 4.96 11000.0 1
Cytochrome P450 1A2
CHEMBL3356
IC50 4.88 4.88 13300.0 1
Leishmania braziliensis
CHEMBL612878
IC50 4.72 4.72 19080.0 1
Adenosine receptor A1
CHEMBL318
Ki 4.71 4.71 19600.0 1
Beta-lactamase
CHEMBL2026
IC50 4.7 4.7 20000.0 3
Leishmania chagasi
CHEMBL612790
IC50 4.66 4.555 22000.0 2
Leishmania major
CHEMBL612879
IC50 4.66 4.66 21830.0 1
Quinolone resistance protein NorA
CHEMBL5114
IC50 4.64 4.64 22800.0 1
Leishmania amazonensis
CHEMBL612877
IC50 4.58 4.58 26500.0 1
Malate dehydrogenase, cytoplasmic
CHEMBL3560
IC50 4.3 4.3 50000.0 1
Adenosine receptor A2a
CHEMBL302
Ki 4.2 4.2 63800.0 1
LLC-MK2
CHEMBL614691
IC50 4.14 4.14 71590.0 1
ATP-binding cassette sub-family C member 4
CHEMBL1743128
IC50 4.06 4.06 88000.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 345.26 ng.hr.mL-1 Homo sapiens
CL 37.0 mL.min-1.kg-1 Canis lupus familiaris
CL 115.0 mL.min-1.kg-1 Rattus norvegicus
CL 48.0 mL.min-1.kg-1 Canis lupus familiaris
CL 7.0 mL.min-1.kg-1 Homo sapiens
CL 11.0 mL.min-1.kg-1 Homo sapiens
CL 10.9 mL.min-1.kg-1 Homo sapiens
CL 11.0 mL.min-1.kg-1 Homo sapiens
CL 48.0 mL.min-1.kg-1 Canis lupus familiaris
CL 115.0 mL.min-1.kg-1 Rattus norvegicus
CL 7.0 mL.min-1.kg-1 Homo sapiens
CL 11.0 mL.min-1.kg-1 Homo sapiens
CL 27.0 mL.min-1.kg-1 Macaca
CL 300.0 mL.min-1.g-1 Homo sapiens
CL 150.0 uL.min-1.(10^6cells)-1 Rattus norvegicus
CL 150.0 uL.min-1.(10^6cells)-1 Homo sapiens
Cmax 184.0 nM -
Cmax 81.0 nM Homo sapiens
F 49.0 % Homo sapiens
Fu 0.01 - Homo sapiens
Fu 0.01 - Homo sapiens
Fu 0.095 - Homo sapiens
Fu 0.006 - Homo sapiens
Fu 0.006 - Macaca fascicularis
Fu 0.006 - Canis lupus familiaris
Fu 0.004 - Cavia porcellus
Fu 0.004 - Mus musculus
Fu 0.008 - Rattus norvegicus
Fu 0.003 - Not specified
Fu 0.008 - Not specified

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Rattus norvegicus IC50 = 0.026 nM 10.59 Calcium antagonistic activity was evaluated by in vitro inhibition of [3H]nitren... 2542561
Sus scrofa IC50 = 0.3 nM 9.52 Calcium antagonistic activity was evaluated from the inhibition of CaCl2-induced... 2542561
Voltage-gated L-type calcium channel Ki = 0.84 nM 9.08 Inhibition of [3H]nitrendipine binding to L-type calcium channel from rat brain ... 3023614
Voltage-gated L-type calcium channel IC50 = 2.66 nM 8.57 Inhibition of [3H]nitrendipine binding to L-type calcium channels of rat cerebra... 2552119
Voltage-dependent L-type calcium channel subunit alpha-1C IC50 = 250.0 nM 6.6 Inhibition of L-type calcium channel measured using 2-electrode voltage-clamp in... 22761000
Cytochrome P450 2C9 Ki = 280.0 nM 6.55 Inhibition of human cytochrome P450 2C9 14761192
Cytochrome P450 2C9 IC50 = 378.0 nM 6.42 Inhibition of CYP2C9 in human liver microsomes using diclofenac as substrate aft... 22328583
Cytochrome P450 3A4 IC50 = 380.0 nM 6.42 Inhibition of CYP3A4 in human liver microsomes using testosterone substrate by L... 23033255
Cytochrome P450 3A4 IC50 = 420.0 nM 6.38 Inhibition of human cytochrome P450 3A4 12699389
Transient receptor potential cation channel subfamily A member 1 EC50 = 500.0 nM 6.3 Agonist activity at mouse TRPA1 channel expressed in CHO cells assessed as incre... 20356305
Cytochrome P450 2C19 IC50 = 560.0 nM 6.25 Inhibition of CYP2C19 in human liver microsomes using omeprazole substrate by LC... 23033255
Cytochrome P450 2C9 IC50 = 660.0 nM 6.18 Inhibition of CYP2C9 in human liver microsomes using tolbutamide substrate by LC... 23033255
ATP-dependent translocase ABCB1 IC50 = 950.0 nM 6.02 Inhibition of P-glycoprotein using calcein-AM assay transfected in porcine PBCEC 12699389
Adrenergic receptor alpha-2 IC50 = 1400.0 nM 5.85 Alpha-2-adrenolytic activity was assessed from the ability to inhibit [3H]yohimb... 2542561
Rattus norvegicus IC50 = 1400.0 nM 5.85 Calcium antagonistic activity determined by the inhibitory effect on high-potass... 11206476
Cytochrome P450 2C8 IC50 = 1560.0 nM 5.81 Inhibition of CYP2C8 in human liver microsomes using paclitaxel as substrate aft... 22328583
Cytochrome P450 2D6 IC50 = 1590.0 nM 5.8 Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substra... 22328583
Cytochrome P450 2J2 IC50 = 1690.0 nM 5.77 Inhibition of human recombinant CYP2J2 assessed as reduction in astemizole O-dem... 23033255
Cytochrome P450 2D6 IC50 = 1780.0 nM 5.75 Inhibition of CYP2D6 in human liver microsomes using bufuralol substrate by LC-M... 23033255
ATP-dependent translocase ABCB1 IC50 = 2300.0 nM 5.64 TP_TRANSPORTER: inhibition of Calcein-AM efflux in MDR1-expressing LLC-PK1 cells 12699389

Literature References

PubMed DOI Target Context # Activities
16472241 10.2174/1570163043334794 Hepatotoxicity 18
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
18024584 10.1073/pnas.0709695104 H4 12
15646539 10.1016/s0399-8320(04)95062-2 Unchecked 11
12699389 10.1021/jm021012t ATP-dependent translocase ABCB1 10
21051535 10.1124/dmd.110.034629 ADMET 9
20070106 10.1021/jm901371v Homo sapiens 8
15646539 10.1016/s0399-8320(04)95062-2 NON-PROTEIN TARGET 8
15920768 10.1002/jps.20373 ADMET 8
11716514 10.1006/bbrc.2001.6000 ATP-dependent translocase ABCB1 7
11602674 - ATP-dependent translocase ABCB1 7
28117588 10.1021/acs.jmedchem.6b01439 Staphylococcus aureus 6
18223646 10.1038/nchembio.65 Eukaryotic peptide chain release factor GTP-binding subunit 6
2552119 10.1021/jm00130a029 Canis familiaris 5
13678405 10.1021/jm030266r Beta-lactamase 5
21474681 10.1124/dmd.111.038778 Brain 5
21098647 10.1124/dmd.110.036988 ADMET 5
8709132 10.1021/jm9600205 Adenosine receptor A3 4
18426954 10.1124/dmd.108.020479 ADMET 4
14521410 10.1021/jm030191r Beta-lactamase 4

Data from ChEMBL 36 via Core Engine