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Compound Detail

CHEMBL1471

APREPITANT
💊 Approved Drug
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💊 Approved Drug
C[C@@H](O[C@H]1OCCN(Cc2n[nH]c(=O)[nH]2)[C@H]1c1ccc(F)cc1)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID CHEMBL1471
Name APREPITANT
Phase Approved
Structure Type MOL
InChI Key ATALOFNDEOCMKK-OITMNORJSA-N
Therapeutic ✓ Yes

Known Names

Aponvie Aprepitant Cinvanti Emend L-754,030 MK-0869 MK-869 NSC-748825 Ono-7436
11
Targets
31
Activities
3
Assay Types
25
PK Parameters
20
Publications
9
Known Names
20
Indications
1
Mechanisms

Molecular Properties

534.4
MW (Da)
4.95
ALogP
5
HBA
2
HBD
83.2
PSA (Ų)
0.44
QED
1
Ro5 Violations
6
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2003
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral Parenteral

Flags

First in Class Chemical Probe
USAN Stem -tant
USAN Year 2000

Extended Properties

Molecular Formula C23H21F7N4O3
MW 534.43
Aromatic Rings 3
Heavy Atoms 37
NP-Likeness -0.94

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Neurokinin 1 receptor antagonist ANTAGONIST Substance-P receptor ✓ ✓

Indications

Nausea Nausea Neoplasms Postoperative Nausea and Vomiting Postoperative Nausea and Vomiting Postoperative Nausea and Vomiting Vomiting Carcinoma, Hepatocellular Carcinoma, Non-Small-Cell Lung Depressive Disorder, Major Dysmenorrhea Multiple Myeloma Neoplasms, Germ Cell and Embryonal Alcoholism Cocaine-Related Disorders Gastroparesis Leukemia, Myeloid, Acute Marijuana Abuse Pain Pruritus

ATC Classification

A04AD12
aprepitant
Level 1: ALIMENTARY TRACT AND METABOLISM
Level 2: ANTIEMETICS AND ANTINAUSEANTS

Activity Summary

IC50 26 meas. best 10.05
Ki 4 meas. best 10.1
Kd 1 meas. best 8.08

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Substance-P receptor
CHEMBL249
 Ki 10.1 9.24 0.1 3
Substance-P receptor
CHEMBL1764942
 IC50 10.05 10.05 0.1 1
Substance-P receptor
CHEMBL249
 IC50 10.05 9.9458 0.1 12
Substance-P receptor
CHEMBL249
 Kd 8.08 8.08 8.3 1
Cytochrome P450 3A4
CHEMBL340
 IC50 7.7 7.61 20.0 4
Neuromedin-K receptor
CHEMBL4429
 Ki 6.34 6.34 454.1 1
Psychosine receptor
CHEMBL3714081
 IC50 5.73 5.73 1873.6 1
G-protein coupled receptor 183
CHEMBL3259470
 IC50 5.35 5.35 4512.7 1
G-protein coupled receptor 35
CHEMBL1293267
 IC50 5.21 5.21 6238.5 1
fMet-Leu-Phe receptor
CHEMBL3359
 IC50 4.94 4.94 11590.1 1
Unchecked
CHEMBL612545
 IC50 4.82 4.82 15100.0 1
A549
CHEMBL392
 IC50 4.74 4.74 18300.0 2
MRC5
CHEMBL614181
 IC50 4.54 4.54 28900.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 570.0 ng.hr.mL-1 Rattus norvegicus
AUC 6300.0 ng.hr.mL-1 Rattus norvegicus
AUC 22000.0 ng.hr.mL-1 Rattus norvegicus
AUC 2700.0 ng.hr.mL-1 Rattus norvegicus
AUC 6400.0 ng.hr.mL-1 Rattus norvegicus
AUC 1100.0 ng.hr.mL-1 Canis lupus familiaris
AUC 8900.0 ng.hr.mL-1 Canis lupus familiaris
AUC 370000.0 ng.hr.mL-1 Canis lupus familiaris
AUC 3800.0 ng.hr.mL-1 Canis lupus familiaris
AUC 38000.0 ng.hr.mL-1 Canis lupus familiaris
CL 1.0 mL.min-1.kg-1 Homo sapiens
F 53.0 % Rattus norvegicus
F 40.0 % Canis lupus familiaris
F 62.5 % Homo sapiens
Fu 0.05 - Homo sapiens
Fu 0.001 - Homo sapiens
Fu 0.002 - Macaca fascicularis
Fu 0.001 - Canis lupus familiaris
Fu 0.001 - Cavia porcellus
Fu 0.002 - Mus musculus
Fu 0.001 - Rattus norvegicus
Fu 0.001 - Rattus norvegicus
MRT 16.0 hr Homo sapiens
T1/2 13.0 hr Homo sapiens
T1/2 2.567 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Substance-P receptor Ki = 0.07943 nM 10.1 Binding affinity to NK1 receptor (unknown origin) 24374277
Substance-P receptor IC50 = 0.09 nM 10.05 In vitro inhibition of binding of [125I]-substance P to tachykinin receptor 1 11708932
Substance-P receptor IC50 = 0.09 nM 10.05 Displacement of [125I]-labeled SP from the human Tachykinin receptor 1 expressed... 9804700
Substance-P receptor IC50 = 0.09 nM 10.05 Displacement of [125I]-labeled SP from human NK-1 receptor expressed in CHO cell... 34213340
Substance-P receptor IC50 = 0.09 nM 10.05 Antagonist activity at human neurokinin receptor 1 assessed as inhibition of 125... 30243589
Substance-P receptor IC50 = 0.09 nM 10.05 Displacement of [125I]-substance P from gerbil NK1 receptor expressed in HEK293 ... 26048800
Substance-P receptor IC50 = 0.09 nM 10.05 Antagonist activity at NK1 receptor (unknown origin) 24075145
Substance-P receptor IC50 = 0.09 nM 10.05 Inhibition of NK1 receptor 18570365
Substance-P receptor IC50 = 0.09 nM 10.05 Displacement of [125I]SP from human NK1 receptor expressed in CHO cells 17723300
Substance-P receptor IC50 = 0.09 nM 10.05 Displacement of [125I]SP from human cloned NK1 receptor expressed in CHO cells 16831551
Substance-P receptor IC50 = 0.09 nM 10.05 Displacement of [125I]SP from human cloned NK1 receptor expressed in CHO cells 16824752
Substance-P receptor IC50 = 0.09 nM 10.05 compounds were evaluated for inhibitory activity against human Tachykinin recept... 10737756
Substance-P receptor IC50 = 0.1 nM 10.0 Binding affinity against human Tachykinin receptor 1 expressed in CHO cells usin... 12372532
Substance-P receptor Ki = 0.8 nM 9.1 Displacement of radioligand [3H]SP from human NK1 F264Y6.51 mutant expressed in ... 22574973
Substance-P receptor IC50 = 1.41 nM 8.85 Antagonist activity at NK1R (unknown origin) in presence of endogenous SP ligand... 34236855
Substance-P receptor Ki = 3.0 nM 8.52 Displacement of radioligand [3H]SP from wild type human NK1 receptor expressed i... 22574973
Substance-P receptor Kd = 8.318 nM 8.08 Competitive inhibition of human NK1 F264Y6.51 mutant expressed in HEK293 cells a... 22574973
Cytochrome P450 3A4 IC50 = 20.0 nM 7.7 Inhibition Assay: A dimethyl sulfoxide (DMSO) solution of a test compound with a... -
Cytochrome P450 3A4 IC50 = 20.0 nM 7.7 Inhibitory Effect on CYP3A4: A dimethyl sulfoxide (DMSO) solution of a test comp... -
Cytochrome P450 3A4 IC50 = 20.0 nM 7.7 CYP3A4 Inhibition Assay: A dimethyl sulfoxide (DMSO) solution of a test compound... -

Literature References

PubMed DOI Target Context # Activities
9804700 10.1021/jm980299k Mustela putorius furo 16
10737756 10.1021/jm990617v Homo sapiens 15
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
10737756 10.1021/jm990617v Rattus norvegicus 10
10737756 10.1021/jm990617v Canis familiaris 10
- 10.6019/CHEMBL5058564 Fibroblast 8
- 10.6019/CHEMBL5058564 U2OS 8
- 10.6019/CHEMBL5058564 HEK-293T 7
10737756 10.1021/jm990617v Mustela putorius furo 7
- 10.6019/CHEMBL5209801 Sphingosine 1-phosphate receptor 1 5
- 10.6019/CHEMBL5209801 CX3C chemokine receptor 1 5
- 10.6019/CHEMBL5209801 N-formyl peptide receptor 2 5
21474681 10.1124/dmd.111.038778 Brain 5
- 10.6019/CHEMBL5209801 Apelin receptor 5
22574973 10.1021/jm2017072 Substance-P receptor 5
- 10.6019/CHEMBL5209801 Type-1 angiotensin II receptor 5
- 10.6019/CHEMBL5209801 Free fatty acid receptor 4 5
- 10.6019/CHEMBL5209801 Alpha-2A adrenergic receptor 5
- 10.6019/CHEMBL5209801 Beta-2 adrenergic receptor 5
- 10.6019/CHEMBL5209801 Glucagon-like peptide 1 receptor 5

Data from ChEMBL 36 via Core Engine