Home Neuronal Signaling Neurokinin Receptor antagonist Aprepitant

연구용

Aprepitant Neurokinin Receptor antagonist

제품 번호S1189

Aprepitant is a potent and selective neurokinin-1 receptor antagonist with IC50 of 0.1 nM. This compound reduces levels of pro-inflammatory cytokines including G-CSF, IL-6, IL-8 and TNFα. It inhibits HIV infection of human macrophages.
Aprepitant Neurokinin Receptor antagonist Chemical Structure

화학 구조

분자량: 534.43

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품질 관리 (Quality Control)

배치: 순도: 99.91%
99.91

세포 배양, 처리 및 작업 농도
(Cell Culture, Treatment & Working Concentration)

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
CHO cells Function assay Displacement of [125I]SP from human NK1 receptor expressed in CHO cells, IC50=9e-05 μM
HEK293 cell Function assay Displacement of [125I]-substance P from gerbil NK1 receptor expressed in HEK293 cell membranes incubated for 30 mins by liquid scintillation counting method, IC50=9e-05 μM
HEK293 cell Function assay Noncompetitive inhibition of wild type human NK1 receptor expressed in HEK293 cells assessed as decrease in SP1-induced [3H]IP accumulation after 20 mins
클릭하여 더 많은 세포주 실험 데이터 보기

화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 534.43 화학식

C23H21F7N4O3

 보관 (수령일로부터)
CAS 번호 170729-80-3 SDF 다운로드 원액 보관

동의어 MK-0869, L-754030 Smiles CC(C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)OC2C(N(CCO2)CC3=NNC(=O)N3)C4=CC=C(C=C4)F

용해도 (Solubility)

In vitro
배치:

DMSO : 107 mg/mL (200.21 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Ethanol : 15 mg/mL

Water : Insoluble

몰농도 계산기

질량 농도 부피 분자량
희석 계산기 분자량 계산기

In vivo
배치:

생체 내 제형 계산기 (투명한 용액)

1단계: 아래 정보 입력 (권장: 실험 중 손실을 고려하여 추가 동물 포함)

mg/kg g μL

2단계: 생체 내 제형 입력 (이것은 계산기일 뿐 제형이 아닙니다. 용해도 섹션에 생체 내 제형이 없는 경우 먼저 당사에 문의하십시오.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

계산 결과:

작업 농도: mg/ml;

DMSO 원액 준비 방법: mg 약물 사전 용해 μL DMSO ( 원액 농도 mg/mL, 농도가 해당 약물 배치의 DMSO 용해도를 초과하는 경우 먼저 당사에 문의하십시오. )

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가μL PEG300, 혼합하고 투명하게 한 다음 추가μL Tween 80, 혼합하고 투명하게 한 다음 추가 μL ddH2O, 혼합하고 투명하게 합니다.

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가 μL 옥수수 기름, 혼합하고 투명하게 합니다.

참고: 1. 다음 용매를 추가하기 전에 액체가 투명한지 확인하십시오.
2. 용매를 순서대로 추가해야 합니다. 다음 용매를 추가하기 전에 이전 추가에서 얻은 용액이 투명한 용액인지 확인해야 합니다. 와동, 초음파 또는 뜨거운 물 중탕과 같은 물리적 방법을 사용하여 용해를 도울 수 있습니다.

작용 메커니즘 (Mechanism of Action)

Targets/IC50/Ki
G-CSF
IL-6
IL-8
TNFα
Neurokinin-1 receptor
(Cell-free assay)
0.1 nM
시험관 내(In vitro)

Aprepitant antagonizes the effects of substance P by binding to NK-1 receptors primarily in the CNS, but also in the periphery. This compound, at concentrations of 0.1 nM displaces 50% of substance P from hNK1 receptors transfected in CHO or COS cells. In radioligand binding assays, it is 3000-fold selective for the human cloned NK1 receptor versus the human cloned NK3 receptor and >50,000-fold selective over the human cloned NK2 receptor. In a range of assays at other human cloned G–protein coupled receptors, this chemical retains >50,000-fold selectivity for the human cloned NK1 receptor. It is inactive in human monoamine oxidase A and B assays and at human serotonin 5–HT1A, 5–HT2A, 5–HT2c, 5–HT3, 5–HT5, 5–HT6, and 5–HT7 receptors (IC50>3 μM). In the PANLABS panel of radioligand binding screens using native animal tissues, this compound inhibits [3H]substance P binding to native NK1 receptors in rat submaxillary gland; there are no significant interactions of it with any other native animal G–protein coupled receptors or ion channels examined in the PANLABS screen. It is inactive in monoamine uptake site (NE, 5–HT, DA) counterscreens using human and animal tissues (IC50> 3 μM)

생체 내(In vivo)

Aprepitant crosses the blood–brain barrier and occupied NK-1 receptors in the brain. This compound has been shown to inhibit both acute and delayed emesis induced by cytotoxic chemotherapeutic such as cisplatin by blocking substance P. It (3 mg/kg i.v. or p.o.) inhibits the emetic response to cisplatin (10 mg/kg i.v.). The anti-emetic protection afforded by this chemical (0.1 mg/kg i.v.) is enhanced by combined treatment with either dexamethasone (20 mg/kg i.v.) or the 5–HT3 receptor antagonist ondansetron (0.1 mg/kg i.v.). In a model of acute and delayed emesis, ferrets are dosed with cisplatin (5 mg/kg i.p.) and the retching and vomiting response recorded for 72 h. Pretreatment with it (4–16 mg/kg p.o.) dose-dependently inhibits the emetic response to cisplatin. Once daily treatment with this compound (2 and 4 mg/kg p.o.) completely prevents retching and vomiting in all ferrets tested. Further when daily dosing began at 24 h after cisplatin injection, when the acute phase of emesis had already become established, it (4 mg/kg p.o. at 24 and 48 h after cisplatin) prevents retching and vomiting in three out of four ferrets.

This chemical also plays a key part in transmission of pain impulses from the peripheral receptors to the CNS and is involved in various behavioural, neurochemical and cardiovascular responses to stress.

참조

임상시험 정보 (Clinical Trial Information)

(데이터 출처 https://clinicaltrials.gov, 업데이트 날짜 2024-05-22)

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT05755659 Recruiting
Neoplasms
Xijing Hospital
 July 15 2022 Not Applicable
NCT04075955 Completed
Chemotherapy-induced Nausea and Vomiting
CR-CSSS Champlain-Charles-Le Moyne
 April 29 2019 Phase 3
NCT03683225 Active not recruiting
Idiopathic Parkinson Disease
Chase Therapeutics Corporation
 April 1 2019 Phase 2
NCT03889366 Completed
Healthy
Nuformix Technologies Limited
 March 20 2019 Phase 1