Devimistat (CPI-613)

Catalog No.S2776 Batch:S277603

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Technical Data

Formula

C22H28O2S2
Molecular Weight 388.59 CAS No. 95809-78-2
Solubility (25°C)* In vitro DMSO 78 mg/mL (200.72 mM)
Ethanol 78 mg/mL (200.72 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
3.9mg/ml 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 95% Corn oil
0.65mg/ml 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. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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, 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]
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]

Protocol (from reference)

Kinase Assay:

[1]
  • 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 Assay:

[2]
  • 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.
Animal Study:

[1]
  • 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.

Selleck's Devimistat (CPI-613) has been cited by 25 publications

Small molecules targeting selective PCK1 and PGC-1α lysine acetylation cause anti-diabetic action through increased lactate oxidation [ Cell Chem Biol, 2024, 31(10):1772-1786.e5] PubMed: 39341205
The Fe-S cluster assembly protein IscU2 increases α-ketoglutarate catabolism and DNA 5mC to promote tumor growth [ Cell Discov, 2023, 9(1):76] PubMed: 37488138
Maternal vitamin B1 is a determinant for the fate of primordial follicle formation in offspring [ Nat Commun, 2023, 10.1038/s41467-023-43261-8] PubMed: 37973927
Induction of functional neutrophils from mouse fibroblasts by thymidine through enhancement of Tet3 activity [ Cell Mol Immunol, 2022, 10.1038/s41423-022-00842-9] PubMed: 35301470
Microglial hexokinase 2 deficiency increases ATP generation through lipid metabolism leading to β-amyloid clearance [ Nat Metab, 2022, 4(10):1287-1305] PubMed: 36203054
Lactate is an epigenetic metabolite that drives survival in model systems of glioblastoma [ Mol Cell, 2022, 82(16):3061-3076.e6] PubMed: 35948010
Chronic activation of pDCs in autoimmunity is linked to dysregulated ER stress and metabolic responses [ J Exp Med, 2022, 219(11)e20221085] PubMed: 36053251
SHP2 regulates adipose maintenance and adipocyte-pancreatic cancer cell crosstalk via PDHA1 [ J Cell Commun Signal, 2022, 10.1007/s12079-022-00691-1] PubMed: 36074246
Blockade of glutamine-dependent cell survival augments antitumor efficacy of CPI-613 in head and neck cancer [ J Exp Clin Cancer Res, 2021, 40(1):393] PubMed: 34906193
TaurineReprograms Mammary-Gland Metabolism and Alleviates Inflammation Induced byStreptococcus uberisin Mice [ Front. Immunol, 2021, Volume 12] PubMed: None

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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