APREPITANT

APREPITANT : Antagonist of TACR1

Structure

SERP Rating

In Cells

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In Model Organisms

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Information

TACR1

Antagonist

up to 10 nM

Probe Availability:

In Vitro Validations

Uniprot ID: P25103

Target Class: GPCR

Target SubClass: NK-1 Receptor

Potency: Kd

Potency Value: 0.2 nM

Potency Assay: Saturation binding analysis with increasing concentrations of [3H]-Aprepitant using Sf9 membranes

PDB ID for probe-target interaction (3D structure): --

Target aliases:

Substance-P receptor, TAC1R, NK1R, TACR1, NK1R_HUM ...

DOI Reference: 10.1021/jm980299k

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): Selectivity within target family (DOI: 10.1016/S0028-3908(99)00172-0) hNK2 IC50 4500 nM hNK3 IC50 300 nM MK-0869 retained > 50000-fold selectivity for the human cloned NK1 receptor. MK-0869 was inactive in human monoamine oxidase A and B assays and at human serotonin 5-HT1A, 5-HT2A, 5-HT2C, 5-HT3, 5-HT4, 5-HT6 and 5-HT7 (IC50 > 3 µM) Outside target family: Ca2+ IC50 8000 nM Na+ IC50 > 10000 nM

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

Aprepitant is a marketed potent NK1 inhibitor (IC50 = 0.1 nM, human) with good selectivity against NK2 (IC50 = 4.5 µM, human) and NK3 (IC50 = 300 nM, human) determined in a Substance P displacement assay in CHO cells. Ferret and rat NK1 IC50 values were reported to be 0.7 nM and 4 nM respectively. In addition, high selectivity versus several serotonin receptors, L-type calcium channel and monoamine oxidase was reported. Additional selectivity data of aprepitant in a full GPCR panel would further increase the confidence in aprepitant as a selective chemical probe for the NK1 receptor. Aprepitant dose-dependently inhibited substance P-induced IP1 synthesis in hNK1/CHO cells. In vivo PK data is available for several species (ferret, rat, dog). Efficacy was demonstrated in several anti-emetic in vivo models in ferrets.

(last updated: 15 Aug 2024 )