Home Metabolism Dehydrogenase inhibitor Vorasidenib (AG-881)

연구용

Vorasidenib (AG-881) mIDH1/2 inhibitor

제품 번호: S8611

Vorasidenib (AG-881) is an orally available inhibitor of mutated forms of both isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2).
Vorasidenib (AG-881) Dehydrogenase inhibitor Chemical Structure

화학 구조

분자량: 414.74

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품질 관리 (Quality Control)

배치: 순도: 99.99%
99.99

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

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
U87MG Antiproliferative assay 72 hrs Antiproliferative activity against human U87MG cells expressing pLVX-IDH2 R140Q mutant after 72 hrs by celltiterglo reagent based assay, IC50<0.05μM 29847930
TS603 Antiproliferative assay 72 hrs Antiproliferative activity against human TS603 cells harboring IDH2 R140Q mutant after 72 hrs by celltiterglo reagent based assay, IC50<0.05μM 29847930
HT1080 Antiproliferative assay 72 hrs Antiproliferative activity against human HT1080 cells after 72 hrs by celltiterglo reagent based assay, IC50<0.05μM 29847930
Sf9 Function assay 1 hr Inhibition of His-tagged wild type IDH1 (unknown origin)/FLAG-tagged IDH1 R132H mutant heterodimer expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by diaphorase and resazurin addition and measured after 5 mins in presenc, IC50<0.05μM ChEMBL
Sf9 Function assay 1 hr Inhibition of His-tagged wild type IDH1 (unknown origin)/FLAG-tagged IDH1 R132C mutant heterodimer expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by diaphorase and resazurin addition and measured after 5 mins in presenc, IC50<0.05μM ChEMBL
Sf9 Function assay 1 hr Inhibition of DH1 R132H mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 60 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry, IC50<0.05μM ChEMBL
Sf9 Function assay 1 hr Inhibition of DH1 R132C mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 60 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry, IC50<0.05μM ChEMBL
Sf9 Function assay 1 hr Inhibition of IDH2 R140Q mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 16 hrs incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry based cofa, IC50<0.05μM ChEMBL
HT1080 Function assay 48 hrs Inhibition of IDH1 R132H/R132C mutant in human HT1080 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method, IC50<0.05μM ChEMBL
U87MG Function assay 48 hrs Inhibition of IDH1 R132C mutant (unknown origin) expressed in human U87MG cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method, IC50<0.05μM ChEMBL
TS603 Function assay 48 hrs Inhibition of DH1 R132H mutant in human TS603 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method, IC50<0.05μM ChEMBL
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화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 414.74 화학식

C14H13ClF6N6

 보관 (수령일로부터)
CAS 번호 1644545-52-7 SDF 다운로드 원액 보관

동의어 N/A Smiles CC(C(F)(F)F)NC1=NC(=NC(=N1)C2=NC(=CC=C2)Cl)NC(C)C(F)(F)F

용해도 (Solubility)

In vitro
배치:

DMSO : 82 mg/mL (197.71 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Ethanol : 82 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
IDH1
IDH2
시험관 내(In vitro)
Vorasidenib (AG-881) is a pan-IDH1/2 inhibitor that selectively inhibits mutant IDH protein and induces cell differentiation in in vitro and in vivo models. Upon administration, this compound specifically inhibits mutant forms of IDH1 and IDH2, thereby inhibiting the formation of the oncometabolite 2-hydroxyglutarate (2HG) from alpha-ketoglutarate (a-KG). This prevents 2HG-mediated signaling and leads to both an induction of cellular differentiation and an inhibition of cellular proliferation in tumor cells expressing IDH mutations.
생체 내(In vivo)
Vorasidenib (AG-881), which fully penetrates the blood-brain barrier, has been developed and is in early phase I testing for patients with IDH mutation-positive hematologic malignancies and solid tumors, including glioma.
참조

임상시험 정보 (Clinical Trial Information)

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

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT05609994 Not yet recruiting
Low Grade Glioma of Brain
Katy Peters MD PhD|Servier|Duke University
 June 2024 Phase 1
NCT05674474 Completed
Hepatic Impairment
Institut de Recherches Internationales Servier|Servier
 March 14 2023 Phase 1
NCT05484622 Recruiting
Astrocytoma
Institut de Recherches Internationales Servier|Merck Sharp & Dohme LLC|Servier
 January 20 2023 Phase 1
NCT04145128 Completed
Healthy Volunteers
Agios Pharmaceuticals Inc.
 October 2 2019 Phase 1