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Devimistat (CPI-613) Mitochondrial Metabolism Inhibitor

Name: Devimistat (CPI-613)
SKU: S2776
Availability: InStock
Rating: 5 (25 reviews)

Cat.No.S2776

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.

Chemical Structure

Molecular Weight: 388.59

Jump to Mechanism of Action Cell Culture & Working Concentration Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.03%

99.03

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Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	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

Chemical Information, Storage & Stability

Molecular Weight	388.59	Formula	C₂₂H₂₈O₂S₂	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	95809-78-2	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	C1=CC=C(C=C1)CSCCC(CCCCC(=O)O)SCC2=CC=CC=C2

Solubility

In vitro
Batch:

DMSO : 77 mg/mL (198.15 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 77 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	3.900mg/ml (10.04mM)	Taking the 1 mL working solution as an example, add 50 μL of 78 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.650mg/ml (1.67mM)	Taking the 1 mL working solution as an example, add 50 μL of 13 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC₅₀/Ki	PDH ^[1] (NCI-H460 cells) α-ketoglutarate dehydrogenase ^[1] (NCI-H460 cells)
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. ^[1]
Kinase Assay	E1α phosphorylation
Kinase Assay	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.
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. ^[1]
References	[1] https://pubmed.ncbi.nlm.nih.gov/21769686/ [2] https://pubmed.ncbi.nlm.nih.gov/34906193/

Applications

Methods	Biomarkers	Images	PMID
Western blot	pE1α p-AMPK / AMPK		25165100

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

Tech Support

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

Frequently Asked Questions

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

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

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