Home Apoptosis Bcl-2 inhibitor ABT-199 (Venetoclax)

연구용

ABT-199 (Venetoclax) Bcl-2 inhibitor

제품 번호: S8048

Venetoclax (ABT-199, GDC-0199) is a Bcl-2-selective inhibitor with Ki of <0.01 nM in cell-free assays, >4800-fold more selective versus Bcl-xL and Bcl-w, and no activity to Mcl-1. Venetoclax is reported to induce cell growth suppression, apoptosis, cell cycle arrest, and autophagy in triple negative breast cancer MDA-MB-231 cells. Phase 3.
ABT-199 (Venetoclax) Bcl-2 inhibitor Chemical Structure

화학 구조

분자량: 868.44

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품질 관리 (Quality Control)

배치: 순도: 99.97%
99.97

함께 자주 사용되는 제품 ABT-199 (Venetoclax)

A-1210477

This compound and A-1210477 increase MCL1 expression and synergistically induce apoptosis in acute myeloid leukemia (AML) cells, MOLM13/MV4-11/SKM1/OCI-AML5.

Navitoclax (ABT-263)

It, Navitoclax and chemotherapy show promising efficacy and tolerability in patients with relapsed/refractory acute lymphoblastic leukemia.

S63845

It and S63845 significantly delay the time to viral rebound by 4-fold after antiretroviral therapy (ART) cessation in a humanized mouse model of HIV-1 infection.

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

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
CS-THL1 Growth Inhibition Assay 20 nM 72 h DMSO Inhibits cell growth assessed by cell viability 25916698
CS-THL1 Apoptotic Assay 25 nM DMSO Induces apoptosis 25916698
DoGKiT Apoptotic Assay 50 nM DMSO Induces apoptosis 25916698
RS4-11 Growth Inhibition Assay 72 h IC50=0.0402 μM 25649768
NALM-6 Growth Inhibition Assay 72 h IC50>3 μM 25649768
SU-DHL-6 Growth Inhibition Assay 0.8 μM Inhibits cell growth assessed by cell viability 25590803
OCI-Ly19 Growth Inhibition Assay 1 μM Inhibits cell growth assessed by cell viability 25590803
SU-DHL-6 Function Assay 0.75 μM 18 h Increases pro-survival protein MCL-1 expression 25590803
KCL22 Function Assay 2 μM 48 h DMSO Increases DNA fragamentation 25333252
LOUCY Growth Inhibition Assay 10 μM 48 h DMSO IC50=0.0139 μM 25301704
ALL-SIL Growth Inhibition Assay 10 μM 48 h DMSO IC50=0.1803 μM 25301704
CUTLL1 Growth Inhibition Assay 10 μM 48 h DMSO IC50=0.3823 μM 25301704
KOPTK1 Growth Inhibition Assay 10 μM 48 h DMSO IC50=0.6432 μM 25301704
DND-41 Growth Inhibition Assay 10 μM 48 h DMSO IC50=1.9695 μM 25301704
PF-382 Growth Inhibition Assay 10 μM 48 h DMSO IC50=2.1824 μM 25301704
KARPAS-45 Growth Inhibition Assay 10 μM 48 h DMSO IC50=3.2225 μM 25301704
PEER Growth Inhibition Assay 10 μM 48 h DMSO IC50=4.6403 μM 25301704
CX-1 Growth Inhibition Assay 100 μM 72 h IC50=6.7 μM 25208882
LS147T Growth Inhibition Assay 100 μM 72 h IC50=29.5 μM 25208882
HL-60 Growth Inhibition Assay 48 h IC50<1 μM 24346116
MOLM-13 Growth Inhibition Assay 48 h IC50<1 μM 24346116
OCI-AML2 Growth Inhibition Assay 48 h IC50<1 μM 24346116
Kasumi-1 Growth Inhibition Assay 48 h IC50<1 μM 24346116
KG-1 Growth Inhibition Assay 48 h IC50<1 μM 24346116
THP-1 Growth Inhibition Assay 48 h IC50<1 μM 24346116
MOLM-14 Growth Inhibition Assay 48 h IC50<1 μM 24346116
MOLM-13 Apoptotic Assay 50 nM 24 h Apoptosis induction 24346116
HSB Growth Inhibition Assay 10 μM 48 h DMSO IC50=4.448 μM 24342948
MOLT4 Growth Inhibition Assay 10 μM 48 h DMSO IC50=4.154 μM 24342948
SKW-3/KE-37 Growth Inhibition Assay 10 μM 48 h DMSO IC50=0.712 μM 24342948
SUPT-11 Growth Inhibition Assay 10 μM 48 h DMSO IC50=4.473 μM 24342948
JURKAT Growth Inhibition Assay 10 μM 48 h DMSO IC50=4.893 μM 24342948
CCRF-CEM Growth Inhibition Assay 10 μM 48 h DMSO IC50=1.360 μM 24342948
LOUCY Apoptotic Assay 2 μM 48 h DMSO Apoptosis induction 24342948
RS4:11 Cytotoxicity assay 29407973
RS4:11 MTS assay 72 h 30278333
RS4:11 MTS assay 28926247
Toledo MTS assay 72 h 30278333
NCI60 SRB assay 48 h 27994761
RS4:11 MTT assay 24 h 29453135
melanoma SRB assay 48 h 27994761
leukemia SRB assay 48 h 27994761
renal cancer SRB assay 48 h 27994761
non-small cell lung cancer SRB assay 48 h 27994761
breast cancer SRB assay 48 h 27994761
colon cancer SRB assay 48 h 27994761
ovarian cancer SRB assay 48 h 27994761
CNS cancer SRB assay 48 h 27994761
prostate cancer SRB assay 48 h 27994761
Remb1 MTT assay 24 h 29453135
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화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 868.44 화학식

C45H50ClN7O7S

 보관 (수령일로부터)
CAS 번호 1257044-40-8 SDF 다운로드 원액 보관

동의어 GDC-0199 Smiles CC1(CCC(=C(C1)C2=CC=C(C=C2)Cl)CN3CCN(CC3)C4=CC(=C(C=C4)C(=O)NS(=O)(=O)C5=CC(=C(C=C5)NCC6CCOCC6)[N+](=O)[O-])OC7=CN=C8C(=C7)C=CN8)C

용해도 (Solubility)

In vitro
배치:

DMSO : 100 mg/mL (115.14 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
Re-engineered version of ABT-263 (Navitoclax).
Targets/IC50/Ki
Bcl-2
(Cell-free assay)
<0.01 nM(Ki)
시험관 내(In vitro)
Venetoclax (ABT-199) shows less sensitivity to Bcl-xL, Mcl-1 and Bcl-w with Ki of 48 nM, > 444 nM and 245 nM, respectively. It potently inhibits FL5.12-Bcl-2 cells, RS4;11 cells with EC50 of 4 nM and 8 nM, while shows low activity against FL5.12-Bcl-xL cells with EC50 of 261 nM. This compound induces a rapid apoptosis in RS4;11 cells with cytochrome c release, caspase activation, the externalization of phosphatidylserine and the accumulation of sub-G0/G1 DNA. Quantitative immunoblotting reveals that sensitivity to it correlated strongly with the expression of Bcl-2, including NHL, DLBCL, MCL, AML and ALL cell lines. It also induces apoptosis in CLL with an average EC50 of 3.0 nM.
키나아제 분석
Binding affinity assays
Binding affinities (Ki or IC50) of Venetoclax (ABT-199) against different isoforms of Bcl-2 family are determined with competitive fluorescence polarization assays. The following peptide probe/protein pairs are used: f-bad (1 nM) and Bcl-xL (6 nM), f-Bax (1 nM) and Bcl-2 (10 nM), f-Bax (1 nM) and Bcl-w (40 nM), f-Noxa (2 nM) and Mcl-1 (40 nM), and f-Bax (1 nM) and Bcl-2-A1 (15 nM). Its binding affinities for Bcl-xL are also determined using a time-resolved fluorescence resonance energy transfer assay. In this assay, Bcl-xL (1 nM, His tagged) is mixed with 200 nM f-Bak, 1 nM Tb-labeled anti-His antibody, and the compound at room temperature for 30 min. Fluorescence is measured on an Envision plate reader using a 340/35 nm excitation filter and 520/525 (f-Bak) and 495/510 nm (Tb-labeled anti-His antibody) emission filters.
생체 내(In vivo)
Venetoclax (ABT-199) causes a maximal tumor growth inhibition of 95% and tumor growth delay of 152% in RS4;11 xenografts. It also inhibits xenograft growth (DoHH2, Granta-519) as a single agent or in combination with SDX-105 and other agents.
참조

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot Mcl-1 / Bcl-xl / Bcl-2 / Bak / NOXA / Bim PARP / Cleaved PARP / Caspase 3 / Cleaved caspase3 / p-S6(Ser236/236)
S8048-WB1
30663221
Growth inhibition assay Cell death Cell viability
S8048-Growth1
28714472
Immunofluorescence Bcl-2 / Mcl-1
S8048-IF1
28767232

임상시험 정보 (Clinical Trial Information)

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

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT06382168 Not yet recruiting
Leukemia Myeloid Acute
Delta-Fly Pharma Inc.
 May 31 2024 Phase 1|Phase 2
NCT06263387 Not yet recruiting
AML Adult
French Innovative Leukemia Organisation|Acute Leukemia French Association
 April 29 2024 --

자주 묻는 질문 (Frequently Asked Questions)

질문 1:
Could you please offer some advice on the half-life of it ?

답변:
According to the reference (https://www.ncbi.nlm.nih.gov/pubmed/24212376), its half-life in dogs is 12.9 hr.