Home Proteases Secretase inhibitor Avagacestat (BMS-708163)

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Avagacestat (BMS-708163) Secretase inhibitor

제품 번호: S1262

Avagacestat (BMS-708163) is a potent, selective, and orally bioavailable γ-secretase inhibitor of Aβ40 and Aβ42 with IC50 values of 0.3 nM and 0.27 nM, respectively. This compound demonstrates a 193-fold selectivity against Notch and has reached Phase 2 clinical trials.
Avagacestat (BMS-708163) Secretase inhibitor Chemical Structure

화학 구조

분자량: 520.88

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품질 관리 (Quality Control)

배치: 순도: 99.63%
99.63

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

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
human IMR32 cell Function assay 2 h Inhibition of gamma-secretase in human IMR32 cell membrane using APP as substrate after 2 hrs by ELISA, IC50=0.13 nM
human H4 cells Function assay Inhibition of gamma secretase-mediated amyloid beta42 production in human H4 cells expressing human APP swedish mutant, IC50=0.225 μM
HEK293 cells Function assay Inhibition of gamma-secretase in HEK293 cells after overnight incubation by Western blotting analysis, IC50=1.2 nM
CHO cells Function assay Inhibition of gamma-secretase in CHO cells assessed expressing APPSw assessed as inhibition of amyloid beta(1 to x) secretion after overnight incubation by ELISA, ED50=1.2 nM
human IMR32 cell Function assay 2 h Inhibition of gamma-secretase in human IMR32 cell membrane using Notch as substrate after 2 hrs by ELISA, IC50=1.5 nM
human 786-0 cell Growth inhibition assay Inhibition of human 786-0 cell growth in a cell viability assay, IC50=0.32173 μM
human NCI-H810 cell Growth inhibition assay Inhibition of human NCI-H810 cell growth in a cell viability assay, IC50=0.42598 μM
human IGR-1 cell Growth inhibition assay Inhibition of human IGR-1 cell growth in a cell viability assay, IC50=1.04778 μM
human SK-MEL-3 cell Growth inhibition assay Inhibition of human SK-MEL-3 cell growth in a cell viability assay, IC50=1.49922 μM
human HT-1080 cell Growth inhibition assay Inhibition of human HT-1080 cell growth in a cell viability assay, IC50=2.48764 μM
human NCI-H23 cell Growth inhibition assay Inhibition of human NCI-H23 cell growth in a cell viability assay, IC50=3.9322 μM
human Calu-6 cell Growth inhibition assay Inhibition of human Calu-6 cell growth in a cell viability assay, IC50=4.96014 μM
human CAPAN-1 cell Growth inhibition assay Inhibition of human CAPAN-1 cell growth in a cell viability assay, IC50=5.17886 μM
human COLO-668 cell Growth inhibition assay Inhibition of human COLO-668 cell growth in a cell viability assay, IC50=5.40221 μM
human TE-6 cell Growth inhibition assay Inhibition of human TE-6 cell growth in a cell viability assay, IC50=6.19082 μM
human LCLC-97TM1 cell Growth inhibition assay Inhibition of human LCLC-97TM1 cell growth in a cell viability assay, IC50=10.0886 μM
human CAS-1 cell Growth inhibition assay Inhibition of human CAS-1 cell growth in a cell viability assay, IC50=13.671 μM
human RPMI-2650 cell Growth inhibition assay Inhibition of human RPMI-2650 cell growth in a cell viability assay, IC50=13.8124 μM
human MDA-MB-157 cell Growth inhibition assay Inhibition of human MDA-MB-157 cell growth in a cell viability assay, IC50=14.2431 μM
human KINGS-1 cell Growth inhibition assay Inhibition of human KINGS-1 cell growth in a cell viability assay, IC50=14.3762 μM
human BB49-HNC cell Growth inhibition assay Inhibition of human BB49-HNC cell growth in a cell viability assay, IC50=14.4138 μM
human SK-UT-1 cell Growth inhibition assay Inhibition of human SK-UT-1 cell growth in a cell viability assay, IC50=14.6882 μM
human EW-11 cell Growth inhibition assay Inhibition of human EW-11 cell growth in a cell viability assay, IC50=14.8832 μM
human D-502MG cell Growth inhibition assay Inhibition of human D-502MG cell growth in a cell viability assay, IC50=14.9034 μM
human MMAC-SF cell Growth inhibition assay Inhibition of human MMAC-SF cell growth in a cell viability assay, IC50=15.0833 μM
human NCI-H1648 cell Growth inhibition assay Inhibition of human NCI-H1648 cell growth in a cell viability assay, IC50=15.778 μM
human NCI-H292 cell Growth inhibition assay Inhibition of human NCI-H292 cell growth in a cell viability assay, IC50=15.8806 μM
human NMC-G1 cell Growth inhibition assay Inhibition of human NMC-G1 cell growth in a cell viability assay, IC50=16.6293 μM
human SAS cell Growth inhibition assay Inhibition of human SAS cell growth in a cell viability assay, IC50=17.7812 μM
human HCT-116 cell Growth inhibition assay Inhibition of human HCT-116 cell growth in a cell viability assay, IC50=18.7965 μM
human SBC-5 cell Growth inhibition assay Inhibition of human SBC-5 cell growth in a cell viability assay, IC50=19.03 μM
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화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 520.88 화학식

C20H17ClF4N4O4S

 보관 (수령일로부터)
CAS 번호 1146699-66-2 SDF 다운로드 원액 보관

동의어 N/A Smiles C1=CC(=CC=C1S(=O)(=O)N(CC2=C(C=C(C=C2)C3=NOC=N3)F)C(CCC(F)(F)F)C(=O)N)Cl

용해도 (Solubility)

In vitro
배치:

DMSO : 104 mg/mL (199.66 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : Insoluble

Ethanol : 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)

특징
Appears to be more “notch sparing” than semagacestat (LY450139).
Targets/IC50/Ki
Aβ42
(in H4-8Sw cells)
0.27 nM
Aβ40
(in H4-8Sw cells)
0.3 nM
시험관 내(In vitro)
Avagacestat (BMS-708163) exhibits weaker selectivity for inhibition of Notch processing with 193-fold IC50 value.
생체 내(In vivo)
Avagacestat (BMS-708163) significantly reduces Aβ40 levels for sustained periods in brain, plasma, and cerebrospinal fluid in rats and dogs following oral administration. It has no dose-limiting effects in dogs (3 mg/kg during 6 months), with a high brain to plasma ratio (2.4).
참조

임상시험 정보 (Clinical Trial Information)

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

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT01002079 Completed
Alzheimer Disease
Bristol-Myers Squibb|PRA Health Sciences
 August 2010 Phase 1
NCT01057030 Completed
Alzheimer Disease
Bristol-Myers Squibb
 March 2010 Phase 1
NCT01042314 Completed
Alzheimer Disease
Bristol-Myers Squibb
 January 2010 Phase 1
NCT01039194 Completed
Alzheimer Disease
Bristol-Myers Squibb
 January 2010 Phase 1
NCT00979316 Completed
Alzheimer Disease
Bristol-Myers Squibb
 September 2009 Phase 1
NCT00890890 Terminated
Alzheimer''s Disease
Bristol-Myers Squibb
 May 2009 Phase 2