CPI-613

Catalog No.S2776

CPI-613, a lipoate analog, inhibits mitochondrial enzymes pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase, disrupts tumor cell mitochondrial metabolism. Phase 2.

Price Stock Quantity  
In DMSO USD 170 In stock
USD 110 In stock
USD 770 In stock
Bulk Inquiry

Massive Discount Available

Free Overnight Delivery on all orders over $ 500.

CPI-613 Chemical Structure

CPI-613 Chemical Structure
Molecular Weight: 388.59

Validation & Quality Control

Quality Control & MSDS

Related Compound Libraries

CPI-613 is available in the following compound libraries:

Product Information

  • Compare Dehydrogenase Inhibitors
    Compare Dehydrogenase Products
  • Research Area

Product Description

Biological Activity

Description CPI-613, a lipoate analog, inhibits mitochondrial enzymes pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase, disrupts tumor cell mitochondrial metabolism. Phase 2.
Targets PDH [1] α-ketoglutarate dehydrogenase [1]
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]
Features

Protocol(Only for 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.

Animal Study: [1]

Animal Models BxPC-3 and H460 cells are injected s.c. into the dorsal flank of CD1 nu/nu mice.
Formulation CPI-613 is dissolved in DMSO and then diluted in water.
Dosages ≤25 mg/kg
Administration Administered via i.p.
Solubility 1% DMSO/30% polyethylene glycol/1% Tween 80, 30 mg/mL
* 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.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesBaboonDogMonkeyRabbitGuinea pigRatHamsterMouse
Weight (kg)121031.80.40.150.080.02
Body Surface Area (m2)0.60.50.240.150.050.0250.020.007
Km factor202012128653
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Zachar Z, et al. J Mol Med (Berl). 2011, 89(11), 1137-1148.

Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2014-12-13)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT01520805 Not yet recruiting Acute Myeloid Leukemia (AML)|Myelodysplastic Syndrome (MDS) Cornerstone Pharmaceuticals, Inc. January 2015 Phase 2
NCT01830322 Withdrawn Metastatic Pancreatic Adenocarcinoma Cornerstone Pharmaceuticals, Inc. January 2014 Phase 2
NCT01832857 Recruiting Advanced Solid Tumor Cancer|Metastatic Solid Tumor Cancer Cornerstone Pharmaceuticals, Inc. June 2013 Phase 2
NCT01768897 Recruiting Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities|Adult Acute Myeloid Leukemia With Del(5q)|Adult Acute Myeloid Leukemia With Inv(16)(p13  ...more Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities|Adult Acute Myeloid Leukemia With Del(5q)|Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)|Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)|Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)|Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)|Recurrent Adult Acute Myeloid Leukemia Comprehensive Cancer Center of Wake Forest University|Nat  ...more Comprehensive Cancer Center of Wake Forest University|National Cancer Institute (NCI) January 2013 Phase 1
NCT01034475 Completed Advanced Hematologic Malignancies Comprehensive Cancer Center of Wake Forest University March 2010 Phase 1

view more

Chemical Information

Download CPI-613 SDF
Molecular Weight (MW) 388.59
Formula

C22H28O2S2

CAS No. 95809-78-2
Storage 3 years -20℃Powder
6 months-80℃in solvent (DMSO, water, etc.)
Synonyms
Solubility (25°C) * In vitro DMSO 78 mg/mL (200.72 mM)
Water <1 mg/mL (<1 mM)
Ethanol 78 mg/mL (200.72 mM)
In vivo 1% DMSO/30% polyethylene glycol/1% Tween 80 30 mg/mL
* <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.
Chemical Name 6,8-bis(benzylthio)octanoic acid

Research Area

Tech Support & FAQs

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.

Tel: +1-832-582-8158 Ext:2

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

* Indicates a Required Field

Related Dehydrogenase Products

  • AGI-6780

    AGI-6780 is a potent and selective inhibitor of IDH2 R140Q mutant with IC50 of 23 nM.

  • LB42708

    LB42708 is an orally active farnesyltransferase (FTase) inhibitor with IC50 of 0.8, 1.2, and 2.0 nM toward H-ras, N-ras, and K-ras, respectively.

  • DMOG

    DMOG is an antagonist of α-ketoglutarate cofactor and inhibitor for HIF prolyl hydroxylase.

  • Trilostane

    Trilostane is an inhibitor of 3 β-hydroxysteroid dehydrogenase used in the treatment of Cushing’s syndrome.

  • Mycophenolate Mofetil

    Mycophenolate Mofetil is a non-competitive, selective and reversible inhibitor of inosine monophosphate dehydrogenase I/II with IC50 of 39 nM and 27 nM, respectively.

  • Gimeracil

    Gimeracil is an inhibitor of dihydropyrimidine dehydrogenase, which inhibits the early step in homologous recombination for double strand breaks repair.

  • MK-8245

    MK-8245 is an liver-targeting inhibitor of stearoyl-CoA desaturase (SCD) with IC50 of 1 nM for human SCD1 and 3 nM for both rat SCD1 and mouse SCD1, with anti-diabetic and anti-dyslipidemic efficacy. Phase 2.

    Features:A potent hepatic SCD inhibitor, and does not affect SCD enzyme in skin and eye tissues like other systemically distributed SCD inhibitors.

  • AGI-5198

    AGI-5198 is the first highly potent and selective inhibitor of IDH1 R132H/R132C mutants with IC50 of 0.07 μM/0.16 μM.

  • PluriSIn #1 (NSC 14613)

    PluriSIn #1 is an inhibitor of the stearoyl-coA desaturase 1 (SCD1), which is able to selectively eliminate hPSCs.

  • Methotrexate

    Methotrexate is an antimetabolite and antifolate drug, which acts by inhibiting the metabolism of folic acid.

Recently Viewed Items

Tags: buy CPI-613 | CPI-613 supplier | purchase CPI-613 | CPI-613 cost | CPI-613 manufacturer | order CPI-613 | CPI-613 distributor
Contact Us