Home Metabolism Dehydrogenase inhibitor - Apoptosis related activator Devimistat (CPI-613) For research use only.

Devimistat (CPI-613)

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.

Devimistat (CPI-613) Chemical Structure

Devimistat (CPI-613) Chemical Structure

CAS No. 95809-78-2

Purity & Quality Control

Devimistat (CPI-613) Related Products

Signaling Pathway

Dehydrogenase Signaling Pathways

Dehydrogenase Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description 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
Click to View More Cell Line Experimental Data

Biological Activity

Description 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.
Targets
PDH [1]
(NCI-H460 cells)		 α-ketoglutarate dehydrogenase [1]
(NCI-H460 cells)
In vitro
In vitro

In vitro, CPI-613 produces the selective toxicity against several tumor cell lines including H460 human lung cancer cells and Saos-2 human sarcoma cells with EC50 of 120 μM and 120 μM, respectively. CPI-613 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, CPI-613 (240 μM) also induces both apoptotic and non-apoptotic cell death in H460 human lung cancer and Saos-2 human sarcoma cells. [1]
Kinase Assay E1α phosphorylation
Cells are seeded and grown overnight. Five dishes per test group are treated with CPI-613or solven. 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.
Cell Research Cell lines HN6 cells
Concentrations 100 μM
Incubation Time 24 h
Method

Cells were treated with or without 100 μM CPI-613 for 24 h.
Experimental Result Images Methods Biomarkers Images PMID
Western blot pE1α p-AMPK / AMPK 25165100
In Vivo
In vivo

CPI-613 (25 mg/kg) has potent anticancer activity in a human tumor xenograft model of of a pancreatic tumor cell (BxPC-3). Similarly, CPI-613 (10 mg/kg) also produces significant tumor growth inhibition of H460 human non-small cell lung carcinoma in mouse model. Besides, CPI-613 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. [1]
Animal Research Animal Models BxPC-3 and H460 cells are injected s.c. into the dorsal flank of CD1 nu/nu mice.
Dosages ≤25 mg/kg
Administration Administered via i.p.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
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

Chemical Information & Solubility

Molecular Weight 388.59 Formula

C22H28O2S2
CAS No. 95809-78-2 SDF Download Devimistat (CPI-613) SDF
Smiles C1=CC=C(C=C1)CSCCC(CCCCC(=O)O)SCC2=CC=CC=C2
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 77 mg/mL ( (198.15 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 77 mg/mL

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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Frequently Asked Questions

Question 1:
How to dissolve the compund for in vivo applications?

Answer:
CPI-613 in 1% DMSO+30% polyethylene glycol+1% Tween 80 at 30mg/ml is a suspension, and it is for oral gavage.

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