Home Apoptosis p53 activator Eprenetapopt (APR-246)

연구용

Eprenetapopt (APR-246) p53 activator

제품 번호: S7724

Eprenetapopt (APR-246, PRIMA-1MET) is a small organic molecule that has been shown to restore tumour-suppressor function primarily to mutant p53 and also to induce cell death in various cancer types. It induces apoptosis and autophagy.
Eprenetapopt (APR-246) p53 activator Chemical Structure

화학 구조

분자량: 199.25

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품질 관리 (Quality Control)

배치: 순도: 99.69%
99.69

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

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
NALM-6 Cell viability assay high sensitivity and cell death induction in all TP53mut leukemias, but low APR-246 sensitivity in TP53wt ALL 31073076
UoCB-6 Cell viability assay high sensitivity and cell death induction in all TP53mut leukemias, but low APR-246 sensitivity in TP53wt ALL 31073076
EU-3 Cell viability assay high sensitivity and cell death induction in all TP53mut leukemias, but low APR-246 sensitivity in TP53wt ALL 31073076
MUTZ-5 Cell viability assay high sensitivity and cell death induction in all TP53mut leukemias, but low APR-246 sensitivity in TP53wt ALL 31073076
KOPN-8 Cell viability assay high sensitivity and cell death induction in all TP53mut leukemias, but low APR-246 sensitivity in TP53wt ALL 31073076
RS4;11 Cell viability assay high sensitivity and cell death induction in all TP53mut leukemias, but low APR-246 sensitivity in TP53wt ALL 31073076
SKBR3 Cell cycle assay 5 µM 2 weeks lapatinib in combination with APR-246 caused a lower level of G1 arrest and an increase in the sub-G1 fraction 30743996
BT549 Cell viability assay IC50=3.1 μM 30196236
MDA-MB-468 Cell viability assay IC50=5 μM 30196236
MDA-MB-231 Cell viability assay IC50=4.1 μM 30196236
HCC1143 Cell viability assay IC50=6.8 μM 30196236
MDA-MB-453 Cell viability assay IC50=0.9 μM 30196236
SKBR3 Cell viability assay IC50=5.1 μM 30196236
UACC812 Cell viability assay IC50=11.3 μM 30196236
MCF7 Cell viability assay IC50=31.1 μM 30196236
MCF10A Cell viability assay IC50=5.2 μM 30196236
UMSCC10A Cell viability assay 0-50 μM 72 h suppressed cell survival and bore a modest effect on the killing of HNSCC cells 29348462
FaDu Cell viability assay 0-50 μM 72 h suppressed cell survival and bore a modest effect on the killing of HNSCC cells 29348462
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
클릭하여 더 많은 세포주 실험 데이터 보기

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

분자량 199.25 화학식

C10H17NO3

 보관 (수령일로부터)
CAS 번호 5291-32-7 SDF 다운로드 원액 보관

동의어 PRIMA-1MET Smiles COCC1(C(=O)C2CCN1CC2)CO

용해도 (Solubility)

In vitro
배치:

DMSO : 40 mg/mL (200.75 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : 40 mg/mL

Ethanol : 40 mg/mL

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
Mutant p53
시험관 내(In vitro)

Eprenetapopt (APR-246), also known as PRIMA-1MET, is the first clinical-stage compound that reactivates mutant p53 and induces apoptosis. It is a prodrug that is converted to the active compound methylene quinuclidinone (MQ), a Michael acceptor that binds to cysteine residues in mutant p53 and restores its wild-type conformation.  This compound not only reactivates p53 but also decreases intracellular glutathione levels in a dose-dependent manner. It can trigger apoptosis in a p53-independent manner by inducing ROS and endoplasmic reticulum (ER) stress and by inhibiting thioredoxin reductase 1 (TrxR1). It was also reported that APR-246 induces cell death in myeloma cells independently of p53 status by impairing the GSH/ROS balance. PRIMA-1Met/APR-246 efficiently inhibited the growth of the SCLC cell lines expressing mutant p53 in vitro and induced apoptosis, associated with increased fraction of cells with fragmented DNA, caspase-3 activation, PARP cleavage, Bax and Noxa upregulation and Bcl-2 downregulation in the cells.
생체 내(In vivo)

In a Phase I/II clinical dose-finding study on hematological malignancies and prostate cancer, Eprenetapopt (APR-246) showed a good safety profile, and both clinical and p53-dependent biological responses were observed. It is well tolerated in animal studies, and single treatment with this compound inhibits tumor growth by 21% in mice bearing the aggressively growing A2780-CP20 tumor xenografts.
참조

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot FL-PARP / Cleaved PARP p-p53
S7724-WB1
26452133
Growth inhibition assay Cell viability
S7724-viability1
26452133

임상시험 정보 (Clinical Trial Information)

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

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT04383938 Completed
Bladder Cancer|Gastric Cancer|Non Small Cell Lung Cancer|NSCLC|Urothelial Carcinoma|Advanced Solid Tumor
Aprea Therapeutics
 June 25 2020 Phase 1|Phase 2
NCT04214860 Completed
Myeloid Malignancy
Aprea Therapeutics
 December 13 2019 Phase 1
NCT03391050 Terminated
Melanoma
Aprea Therapeutics|Jules Bordet Institute
 January 18 2018 Phase 1|Phase 2
NCT02999893 Terminated
Oesophageal Carcinoma
Peter MacCallum Cancer Centre Australia
 April 11 2017 Phase 1|Phase 2