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Compound Detail

CHEMBL603

ZAFIRLUKAST
💊 Approved Drug
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💊 Approved Drug
COc1cc(C(=O)NS(=O)(=O)c2ccccc2C)ccc1Cc1cn(C)c2ccc(NC(=O)OC3CCCC3)cc12

Basic Information

ChEMBL ID CHEMBL603
Name ZAFIRLUKAST
Phase Approved
Structure Type MOL
InChI Key YEEZWCHGZNKEEK-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

Accolate ICI 204,219 Ici-204,219 ICI-204219 Zafirlukast
35
Targets
66
Activities
4
Assay Types
27
PK Parameters
20
Publications
5
Known Names
5
Indications
1
Mechanisms

Molecular Properties

575.7
MW (Da)
5.70
ALogP
7
HBA
2
HBD
115.7
PSA (Ų)
0.28
QED
2
Ro5 Violations
8
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1996
Availability Prescription
Chirality Achiral

Routes of Administration

Oral

Flags

Natural Product
USAN Stem -ast
USAN Year 1995

Extended Properties

Molecular Formula C31H33N3O6S
MW 575.69
Aromatic Rings 4
Heavy Atoms 41
NP-Likeness -0.95

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Cysteinyl leukotriene receptor 1 antagonist ANTAGONIST Cysteinyl leukotriene receptor 1

Indications

Asthma Lung Diseases, Obstructive Breast Neoplasms Hypersensitivity Ovarian Neoplasms

ATC Classification

R03DC01
zafirlukast
Level 1: RESPIRATORY SYSTEM
Level 2: DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES

Activity Summary

IC50 41 meas. best 9.59
Ki 13 meas. best 9.52
EC50 9 meas. best 6.15
Kd 3 meas. best 9.5

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Cysteinyl leukotriene receptor 1
CHEMBL1798
IC50 9.59 8.732 0.3 5
Cysteinyl leukotriene receptor
CHEMBL2094254
Ki 9.52 9.11 0.3 2
Cysteinyl leukotriene receptor 1
CHEMBL5645
Ki 9.52 9.1988 0.3 8
Cavia porcellus
CHEMBL369
Kd 9.5 9.5 0.3 1
Cysteinyl leukotriene receptor 1
CHEMBL5645
IC50 9.36 8.4733 0.4 3
Cysteinyl leukotriene receptor 1
CHEMBL1798
Ki 9.06 9.06 0.9 1
U-937
CHEMBL612794
IC50 9.0 9.0 1.0 3
Homo sapiens
CHEMBL372
IC50 9.0 9.0 1.0 1
Cavia porcellus
CHEMBL369
IC50 8.99 8.99 1.0 2
Cysteinyl leukotriene receptor
CHEMBL2094254
IC50 8.3 8.3 5.0 1
Liver
CHEMBL613642
IC50 7.18 7.18 66.2 1
Mitogen-activated protein kinase 14
CHEMBL260
IC50 6.45 6.45 353.0 1
Mitogen-activated protein kinase 1
CHEMBL4040
IC50 6.27 6.27 538.0 1
Nuclear receptor subfamily 1 group I member 2
CHEMBL3401
EC50 6.15 5.1325 710.0 4
Adenosine receptor A3
CHEMBL256
Ki 6.11 6.11 770.0 1
Streptococcus sp. 'group A'
CHEMBL612389
EC50 6.03 6.03 936.0 1
Multidrug and toxin extrusion protein 1
CHEMBL1743126
IC50 5.89 5.89 1300.0 1
Adenosine receptor A3
CHEMBL256
IC50 5.87 5.87 1363.0 1
Bifunctional epoxide hydrolase 2
CHEMBL2409
IC50 5.7 5.7 2000.0 2
Streptokinase A
CHEMBL1293228
EC50 5.69 5.69 2050.0 1
Cytochrome P450 2C9
CHEMBL3397
IC50 5.65 5.65 2257.5 1
Peroxisome proliferator-activated receptor gamma
CHEMBL235
EC50 5.61 5.61 2440.0 1
Cytochrome P450 2C9
CHEMBL3397
Ki 5.6 5.6 2500.0 1
Thromboxane-A synthase
CHEMBL1835
IC50 5.42 5.42 3810.0 1
Bile acid receptor
CHEMBL2047
EC50 5.41 5.41 3900.0 1
Mitogen-activated protein kinase 3
CHEMBL3385
IC50 5.36 5.36 4376.0 1
Epidermal growth factor receptor
CHEMBL203
IC50 5.24 5.24 5751.0 1
Keap1/Nrf2
CHEMBL3038498
IC50 5.23 5.23 5870.0 1
Hepatic sodium/bile acid cotransporter
CHEMBL5287
IC50 5.19 5.19 6500.0 2
Cysteinyl leukotriene receptor 2
CHEMBL4330
IC50 5.13 4.685 7397.0 2
Multidrug and toxin extrusion protein 2
CHEMBL1743127
IC50 5.12 5.12 7600.0 1
Solute carrier family 22 member 2
CHEMBL1743122
IC50 5.01 5.01 9700.0 1
Exportin-1
CHEMBL5661
Kd 5.0 5.0 10000.0 1
Bile salt export pump
CHEMBL6020
IC50 4.96 4.96 11100.0 2
ATP-binding cassette sub-family C member 4
CHEMBL1743128
IC50 4.92 4.92 12100.0 1
Prostaglandin E synthase
CHEMBL5658
IC50 4.74 4.74 18100.0 1
Unchecked
CHEMBL612545
IC50 4.5 4.5 32000.0 1
HGC-27
CHEMBL1075463
IC50 4.36 4.36 44000.0 1
Nuclear receptor subfamily 1 group I member 2
CHEMBL2146315
EC50 4.23 4.23 58400.0 1
ATP-binding cassette sub-family C member 2
CHEMBL5748
IC50 4.23 4.23 58800.0 1
Cytosolic phospholipase A2
CHEMBL3816
IC50 4.07 4.07 85000.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 2458.0 ng.hr.mL-1 Homo sapiens
AUC 2027.0 ng.hr.mL-1 Homo sapiens
AUC 1137.0 ng.hr.mL-1 Homo sapiens
AUC 2073.64 ng.hr.mL-1 Homo sapiens
CL 0.000207 mL.min-1.g-1 Homo sapiens
CL 0.207 uL/min Homo sapiens
CL/F 9.2 L/hr Homo sapiens
CL/F 11.4 L/hr Homo sapiens
CL/F 19.4 L/hr Homo sapiens
Cmax 1313.21 nM Homo sapiens
Cmax 1043.96 nM Homo sapiens
Cmax 566.28 nM Homo sapiens
Cmax 1211.0 nM Homo sapiens
F 25.0 % Rattus norvegicus
F 67.0 % Canis lupus familiaris
F 68.0 % Rattus norvegicus
PPB 99.0 % Homo sapiens
T1/2 13.3 hr Homo sapiens
T1/2 10.0 hr Homo sapiens
T1/2 8.0 hr Homo sapiens
T1/2 8.0 hr Homo sapiens
T1/2 10.0 hr Homo sapiens
Tmax 2.1 hr Homo sapiens
Tmax 2.5 hr Homo sapiens
Tmax 2.0 hr Homo sapiens
Tmax 3.0 hr Homo sapiens
Vss/F 70.0 L Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Cysteinyl leukotriene receptor 1 IC50 = 0.26 nM 9.59 Antagonist activity at human CysLT1 receptor 34767347
Cysteinyl leukotriene receptor Ki = 0.3 nM 9.52 Binding affinity against Cysteinyl leukotriene D4 receptor 8709092
Cysteinyl leukotriene receptor 1 Ki = 0.3 nM 9.52 Displacement of [3H]LTD4 on guinea pig lung parenchymal membranes 2342072
Cysteinyl leukotriene receptor 1 Ki = 0.3 nM 9.52 Binding affinity towards Cysteinyl leukotriene D4 receptor (cysLT1) was measured... 9554877
Cysteinyl leukotriene receptor 1 Ki = 0.3 nM 9.52 Compound was evaluated for its ability to displace [3H]LTD4 from Cysteinyl leuko... 1849993
Cysteinyl leukotriene receptor 1 Ki = 0.3 nM 9.52 Displacement of [3H]LTD4 from cysteinyl leukotriene receptor 1 in Hartley guinea... 28252961
Cavia porcellus Kd = 0.3162 nM 9.5 Compound was evaluated for LTD4 induced guinea pig trachea contraction 8709092
Cysteinyl leukotriene receptor 1 Ki = 0.34 nM 9.47 Inhibition constant for displacement of [3H]LTD4 on guinea pig lung parenchymal ... 8176706
Cysteinyl leukotriene receptor 1 IC50 = 0.44 nM 9.36 Concentration required for inhibition of binding of [3H]LTD4 to guinea pig lung ... -
Cysteinyl leukotriene receptor 1 Ki = 0.865 nM 9.06 DRUGMATRIX: Cysteinyl leukotriene receptor 1 radioligand binding (ligand: [3H]LT... -
U-937 IC50 = 1.0 nM 9.0 Ability to mobilize Ca+2 in LTD4 dependent Ca+2 mobilization assay in differenti... 9873560
Homo sapiens IC50 = 1.0 nM 9.0 Compound was tested for its ability to inhibit calcium influx in human U937 cell... 9934474
U-937 IC50 = 1.0 nM 9.0 Compound was evaluated for influx of calcium mobilization in human U937 cells 9873435
U-937 IC50 = 1.0 nM 9.0 In vitro blocking of extracellular calcium mobilization in human U937 cells 10509933
Cavia porcellus IC50 = 1.03 nM 8.99 In vitro effect of compound on leukotriene-D4 LTD4 (100 nM) induced contraction ... 11738562
Cavia porcellus IC50 = 1.03 nM 8.99 50% inhibitory concentration on the LTD4 (100 nM) induced contraction of guinea-... 12031336
Cysteinyl leukotriene receptor 1 IC50 = 1.731 nM 8.76 DRUGMATRIX: Cysteinyl leukotriene receptor 1 radioligand binding (ligand: [3H]LT... -
Cysteinyl leukotriene receptor 1 IC50 = 1.8 nM 8.74 Inhibition of cysteinyl leukotriene receptor 1 (unknown origin) expressed in HEK... 28252961
Cysteinyl leukotriene receptor 1 IC50 = 1.9 nM 8.72 Antagonist activity at human CysLT1 26200813
Cysteinyl leukotriene receptor Ki = 2.0 nM 8.7 Ability to antagonize LTD4 receptors isolated from guinea pig lung membranes 9873435

Literature References

PubMed DOI Target Context # Activities
16472241 10.2174/1570163043334794 Hepatotoxicity 18
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
15646539 10.1016/s0399-8320(04)95062-2 Unchecked 11
- 10.6019/CHEMBL4689842 HEK-293T 10
- 10.6019/CHEMBL4689842 Fibroblast 9
- 10.6019/CHEMBL4689842 U2OS 9
20966043 10.1124/dmd.110.035105 Nuclear receptor subfamily 1 group I member 2 8
15646539 10.1016/s0399-8320(04)95062-2 NON-PROTEIN TARGET 8
36622814 10.1021/acs.jmedchem.2c01772 Exportin-1 7
36622814 10.1021/acs.jmedchem.2c01772 MDA-MB-453 6
- 10.6019/CHEMBL5209801 CX3C chemokine receptor 1 5
- 10.6019/CHEMBL5209801 Alpha-2A adrenergic receptor 5
- 10.6019/CHEMBL5209801 Apelin receptor 5
- 10.6019/CHEMBL5209801 Type-1 angiotensin II receptor 5
- 10.6019/CHEMBL5209801 Adhesion G-protein coupled receptor F1 5
- 10.6019/CHEMBL5209801 Glucagon-like peptide 1 receptor 5
- 10.6019/CHEMBL5209801 N-formyl peptide receptor 2 5
- 10.6019/CHEMBL5209801 Free fatty acid receptor 4 5
- 10.6019/CHEMBL5209801 C5a anaphylatoxin chemotactic receptor 1 5
- 10.6019/CHEMBL5209801 Glucose-dependent insulinotropic receptor 5

Data from ChEMBL 36 via Core Engine