Home Metabolism Dehydrogenase inhibitor CPI-613 (Devimistat)

연구용

CPI-613 (Devimistat) Mitochondrial Metabolism Inhibitor

제품 번호S2776

Devimistat (CPI-613), a lipoate analog, inhibits mitochondrial enzymes pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase in NCI-H460 cell line, disrupts tumor cell mitochondrial metabolism. CPI-613 induces apoptosis in pancreatic cancer cells. Phase 2.
CPI-613 (Devimistat) Dehydrogenase inhibitor Chemical Structure

화학 구조

분자량: 388.59

바로가기

품질 관리 (Quality Control)

배치: 순도: 99.03%
99.03

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

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY 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
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
클릭하여 더 많은 세포주 실험 데이터 보기

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

분자량 388.59 화학식

C22H28O2S2

 보관 (수령일로부터)
CAS 번호 95809-78-2 SDF 다운로드 원액 보관

동의어 N/A Smiles C1=CC=C(C=C1)CSCCC(CCCCC(=O)O)SCC2=CC=CC=C2

용해도 (Solubility)

In vitro
배치:

DMSO : 77 mg/mL (198.15 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Ethanol : 77 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
PDH
(NCI-H460 cells)
α-ketoglutarate dehydrogenase
(NCI-H460 cells)
시험관 내(In vitro)

Devimistat (CPI-613) produces selective toxicity in vitro against several tumor cell lines, including H460 human lung cancer cells and Saos-2 human sarcoma cells, with EC50 values of 120 μM and 120 μM, respectively. It disrupts H460 cancer cell mitochondrial metabolism, including inhibition of PDH complex activity and loss of mitochondrial membrane potential in a time- and drug dose-dependent fashion. In addition, this compound (240 μM) also induces both apoptotic and non-apoptotic cell death in H460 human lung cancer and Saos-2 human sarcoma cells.

키나아제 분석
E1α phosphorylation
Cells are seeded and grown overnight. Five dishes per test group are treated with Devimistat (CPI-613) or solvent. Cells are lysed in situ with 150 μL lysis buffer A [455 μL Zoom 2D protein solubilizer 1, 2.5μL 1M Tris base, 5μL 100X protease inhibitor cocktail; 5μL 2M DTT] and lysates from all five dishes are pooled in a 1.5 mL microfuge tube and sonicated on ice for 15 passes at 50% power. After a 10-minute incubation at room temperature, 2.5μL of dimethylacrylamide (DMA) are added and lysates are incubated for an additional 10 minutes. 5μL of 2 M DTT are added to neutralize excess DMA. Lysates are centrifuged for 15 minutes and the supernatant is recovered. Then, 40μL of lysate are mixed with 0.8μL pH 3-10 ampholytes, 0.75 μL 2 M DTT and brought up to 150μL with Zoom 2D protein solubilizer 1. 150μL of sample is loaded into IPG runner, and pH 3-10NL IPG strips are added. Strips are soaked overnight at room temperature. A step protocol is used for isoelectric focusing (250V, 20min.; 450V 15min; 750 V 15 min 2000V 30 minutes). For the second dimension, strips are treated for 15 minutes in 1X loading buffer, followed by 15 minutes in 1X loading buffer plus 160 mM iodoacetatic acid. Strips are electrophoresed on NuPAGE 4-12% Bis Tris ZOOM gels. Proteins are blotted onto PVDF 4.5μm membranes. Serines 232, 293 and 300 are targets of the three well-characterized PDK phosphorylation events controlling E1 activity. Equal amounts of protein from treated and mock-treated cells are loaded on gels and western transfers are probed with anti-E1α Ab as an internal matching control or one of the three anti-phospho-E1α Abs.
생체 내(In vivo)

Devimistat (CPI-613) has potent anticancer activity in a human tumor xenograft model of a pancreatic tumor cell (BxPC-3) at 25 mg/kg. Similarly, this compound (10 mg/kg) also produces significant tumor growth inhibition of H460 human non-small cell lung carcinoma in a mouse model. Besides, it produces little or no side-effect toxicity in expected therapeutic dose ranges in large animal models and has the maximum tolerated dose of 100 mg/kg in mice.

참조

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot pE1α p-AMPK / AMPK
S2776-WB1
25165100

임상시험 정보 (Clinical Trial Information)

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

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT05926206 Withdrawn
Metastatic Pancreatic Adenocarcinoma
University of Michigan Rogel Cancer Center
 July 2023 Phase 1|Phase 2
NCT03793140 Active not recruiting
Lymphoma|Leukemia
Memorial Sloan Kettering Cancer Center|City of Hope Medical Center|Massachusetts General Hospital|M.D. Anderson Cancer Center|George Washington University
 December 31 2018 Phase 2

자주 묻는 질문 (Frequently Asked Questions)

질문 1:
How to dissolve it for in vivo applications?

답변:
It is a suspension in 1% DMSO+30% polyethylene glycol+1% Tween 80 at 30mg/ml, and is for oral gavage.