Devimistat | CPI-613 | CAS#95809-78-2 | Antineoplastic

MedKoo Cat#: 200823 | Name: Devimistat

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Devimistat, also known as CPI-613, is a racemic mixture of the enantiomers of a synthetic alpha-lipoic lipoic acid analogue with potential chemopreventive and antineoplastic activities. Although the exact mechanism of action is unknown, alpha-lipoic acid analogue CPI-613 has been shown to inhibit metabolic and regulatory processes required for cell growth in solid tumors. Both enantiomers in the racemic mixture exhibit antineoplastic activity. The mechanism-of-action of CPI-613 appears distinct from the current classes of anti-cancer agents used in the clinic. CPI-613 demonstrates both in vitro and in vivo anti-tumor activity. CPI-613 was known to strongly disrupt tumor mitochondrial metabolism.

Chemical Structure

Devimistat

CAS#95809-78-2

Theoretical Analysis

MedKoo Cat#: 200823

Name: Devimistat

CAS#: 95809-78-2

Chemical Formula: C22H28O2S2

Exact Mass: 388.1531

Molecular Weight: 388.59

Elemental Analysis: C, 68.00; H, 7.26; O, 8.23; S, 16.50

Price and Availability

Size	Price	Availability
10mg	USD 90.00	Ready to ship
25mg	USD 150.00	Ready to ship
100mg	USD 250.00	Ready to ship
200mg	USD 450.00	Ready to ship
500mg	USD 950.00	Ready to ship
1g	USD 1,650.00	Ready to ship
2g	USD 2,950.00	Ready to ship

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Related CAS #

95809-78-2

Synonym

CPI613; CPI-613; CPI 613; Devimistat

IUPAC/Chemical Name

6,8-bis(benzylthio)octanoic acid

InChi Key

ZYRLHJIMTROTBO-UHFFFAOYSA-N

InChi Code

InChI=1S/C22H28O2S2/c23-22(24)14-8-7-13-21(26-18-20-11-5-2-6-12-20)15-16-25-17-19-9-3-1-4-10-19/h1-6,9-12,21H,7-8,13-18H2,(H,23,24)

SMILES Code

O=C(O)CCCCC(SCC1=CC=CC=C1)CCSCC2=CC=CC=C2

Appearance

White solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

CPI-613 disruption of tumor mitochondrial metabolism is followed by efficient commitment to cell death by multiple, apparently redundant pathways, including apoptosis, in all tested cancer cell lines. Further, CPI-613 shows strong antitumor activity in vivo against human non-small cell lung and pancreatic cancers in xenograft models with low side-effect toxicity.

Product Data

Product Data

Certificate of Analysis

View current batch of CoA, Lot#SSC20606

QC Data

View QC data, current batch, lot#SSC20606.

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Devimistat (CPI-613) is a lipoic acid analog that inhibits pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase.

In vitro activity:

To understand whether mitochondrial morphological alterations are responsive to CPI-613, the phenotype of mitochondria in AsPC-1 cells was examined in the presence or absence of CPI-613. TEM analysis showed that CPI-613 dramatically reduced mitochondrial cristae junctions and overall cristae morphology (Fig. 1a). The same phenotype of mitochondria was seen in CPI-613-treated PANC-1 cells (Fig. 1a), indicating that CPI-613 is potent to disrupt mitochondrial structure of pancreatic cancer cells. In addition, there were increased levels of cleaved PARP, cleaved Caspase 3, and Bax in both cell lines treated with CPI-613, coupled with decreased levels of Bcl-2 (Fig. 2c). These data indicate that CPI-613 can effectively induce apoptosis in pancreatic cancer cells. Reference: J Exp Clin Cancer Res. 2020 Apr 28;39(1):73. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187515/

In vivo activity:

OVCAR3 (ovarian cancer) cells were injected s.c. in NOD/SCID (NOD.CB17-Prkdcscid/NCrCrl congenic immunodeficient) mice, and once tumors reached 200 mm3 of volume, the mice were treated weekly i.p. with CPI-613 at a concentration of 12.5 mg/kg. 48 h after the second injection, flow cytometric analysis of tumor cells revealed a decrease in CD133+ and CD117+ tumor cell frequency in CPI-613-treated mice compared with vehicle-treated mice (p-value < 0.001) (Figure 3B lower panel). This effect on CD133+ and CD117+ cell populations was similar to what was observed in the in vitro analysis, confirming the ability of CPI-613 to reduce CSC frequency in the tumor. Reference: Cancers (Basel). 2019 Oct 29;11(11):1678. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896080/

	Solvent	mg/mL	mM
Solubility
	DMSO	88.5	227.75
	Ethanol	77.0	198.15

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 388.59 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Gao L, Xu Z, Huang Z, Tang Y, Yang D, Huang J, He L, Liu M, Chen Z, Teng Y. CPI-613 rewires lipid metabolism to enhance pancreatic cancer apoptosis via the AMPK-ACC signaling. J Exp Clin Cancer Res. 2020 Apr 28;39(1):73. doi: 10.1186/s13046-020-01579-x. PMID: 32345326; PMCID: PMC7187515. 2. Bellio C, DiGloria C, Spriggs DR, Foster R, Growdon WB, Rueda BR. The Metabolic Inhibitor CPI-613 Negates Treatment Enrichment of Ovarian Cancer Stem Cells. Cancers (Basel). 2019 Oct 29;11(11):1678. doi: 10.3390/cancers11111678. PMID: 31671803; PMCID: PMC6896080.

In vitro protocol:

In vivo protocol:

1. Bellio C, DiGloria C, Spriggs DR, Foster R, Growdon WB, Rueda BR. The Metabolic Inhibitor CPI-613 Negates Treatment Enrichment of Ovarian Cancer Stem Cells. Cancers (Basel). 2019 Oct 29;11(11):1678. doi: 10.3390/cancers11111678. PMID: 31671803; PMCID: PMC6896080.

1: Vasan K, Werner M, Chandel NS. Mitochondrial Metabolism as a Target for Cancer Therapy. Cell Metab. 2020 Sep 1;32(3):341-352. doi: 10.1016/j.cmet.2020.06.019. Epub 2020 Jul 14. PMID: 32668195; PMCID: PMC7483781. 2: Anderson R, Miller LD, Isom S, Chou JW, Pladna KM, Schramm NJ, Ellis LR, Howard DS, Bhave RR, Manuel M, Dralle S, Lyerly S, Powell BL, Pardee TS. Phase II trial of cytarabine and mitoxantrone with devimistat in acute myeloid leukemia. Nat Commun. 2022 Mar 30;13(1):1673. doi: 10.1038/s41467-022-29039-4. PMID: 35354808; PMCID: PMC8967916. 3: Mohan A, Griffith KA, Wuchu F, Zhen DB, Kumar-Sinha C, Crysler O, Hsiehchen D, Enzler T, Dippman D, Gunchick V, Achreja A, Animasahun O, Choppara S, Nenwani M, Chinnaiyan AM, Nagrath D, Zalupski MM, Sahai V. Devimistat in Combination with Gemcitabine and Cisplatin in Biliary Tract Cancer: Preclinical Evaluation and Phase Ib Multicenter Clinical Trial (BilT-04). Clin Cancer Res. 2023 Jul 5;29(13):2394-2400. doi: 10.1158/1078-0432.CCR-23-0036. PMID: 37115501; PMCID: PMC10330233. 4: Gao L, Xu Z, Huang Z, Tang Y, Yang D, Huang J, He L, Liu M, Chen Z, Teng Y. CPI-613 rewires lipid metabolism to enhance pancreatic cancer apoptosis via the AMPK-ACC signaling. J Exp Clin Cancer Res. 2020 Apr 28;39(1):73. doi: 10.1186/s13046-020-01579-x. PMID: 32345326; PMCID: PMC7187515. 5: Arnold C, Demuth P, Seiwert N, Wittmann S, Boengler K, Rasenberger B, Christmann M, Huber M, Brunner T, Linnebacher M, Fahrer J. The Mitochondrial Disruptor Devimistat (CPI-613) Synergizes with Genotoxic Anticancer Drugs in Colorectal Cancer Therapy in a Bim-Dependent Manner. Mol Cancer Ther. 2022 Jan;21(1):100-112. doi: 10.1158/1535-7163.MCT-21-0393. Epub 2021 Nov 8. PMID: 34750196. 6: Pardee TS, Luther S, Buyse M, Powell BL, Cortes J. Devimistat in combination with high dose cytarabine and mitoxantrone compared with high dose cytarabine and mitoxantrone in older patients with relapsed/refractory acute myeloid leukemia: ARMADA 2000 Phase III study. Future Oncol. 2019 Oct;15(28):3197-3208. doi: 10.2217/fon-2019-0201. Epub 2019 Sep 12. PMID: 31512500. 7: Anderson R, Pladna KM, Schramm NJ, Wheeler FB, Kridel S, Pardee TS. Pyruvate Dehydrogenase Inhibition Leads to Decreased Glycolysis, Increased Reliance on Gluconeogenesis and Alternative Sources of Acetyl-CoA in Acute Myeloid Leukemia. Cancers (Basel). 2023 Jan 12;15(2):484. doi: 10.3390/cancers15020484. PMID: 36672433; PMCID: PMC9857304. 8: Philip PA, Buyse ME, Alistar AT, Rocha Lima CM, Luther S, Pardee TS, Van Cutsem E. A Phase III open-label trial to evaluate efficacy and safety of CPI-613 plus modified FOLFIRINOX (mFFX) versus FOLFIRINOX (FFX) in patients with metastatic adenocarcinoma of the pancreas. Future Oncol. 2019 Oct;15(28):3189-3196. doi: 10.2217/fon-2019-0209. Epub 2019 Sep 12. PMID: 31512497; PMCID: PMC6854438. 9: Khan HY, Kamgar M, Aboukameel A, Bannoura S, Chung BY, Li Y, Hallak MNA, Philip PA, Tsai S, Luther S, Hall WA, Azmi AS. Targeting Cellular Metabolism With CPI-613 Sensitizes Pancreatic Cancer Cells to Radiation Therapy. Adv Radiat Oncol. 2022 Nov 9;8(1):101122. doi: 10.1016/j.adro.2022.101122. PMID: 36479231; PMCID: PMC9720358. 10: Hu G, Lv M, Guo B, Huang Y, Su Z, Qian Y, Xue X, Liu HK. Immunostimulation with chemotherapy of a ruthenium-arene complex via blockading CD47 signal in chronic myelogenous leukemia cells. J Inorg Biochem. 2023 Jun;243:112195. doi: 10.1016/j.jinorgbio.2023.112195. Epub 2023 Mar 22. PMID: 36996696. 11: Sakuratani T, Takeuchi T, Yasufuku I, Iwata Y, Saigo C, Kito Y, Yoshida K. Downregulation of ARID1A in gastric cancer cells: a putative protective molecular mechanism against the Harakiri-mediated apoptosis pathway. Virchows Arch. 2021 Mar;478(3):401-411. doi: 10.1007/s00428-020-02899-1. Epub 2020 Aug 13. PMID: 32789692. 12: Guardado Rivas MO, Stuart SD, Thach D, Dahan M, Shorr R, Zachar Z, Bingham PM. Evidence for a novel, effective approach to targeting carcinoma catabolism exploiting the first-in-class, anti-cancer mitochondrial drug, CPI-613. PLoS One. 2022 Jun 8;17(6):e0269620. doi: 10.1371/journal.pone.0269620. PMID: 35675354; PMCID: PMC9176802. 13: Gampala S, Shah F, Lu X, Moon HR, Babb O, Umesh Ganesh N, Sandusky G, Hulsey E, Armstrong L, Mosely AL, Han B, Ivan M, Yeh JJ, Kelley MR, Zhang C, Fishel ML. Ref-1 redox activity alters cancer cell metabolism in pancreatic cancer: exploiting this novel finding as a potential target. J Exp Clin Cancer Res. 2021 Aug 10;40(1):251. doi: 10.1186/s13046-021-02046-x. PMID: 34376225; PMCID: PMC8353735. 14: Dörsam B, Fahrer J. The disulfide compound α-lipoic acid and its derivatives: A novel class of anticancer agents targeting mitochondria. Cancer Lett. 2016 Feb 1;371(1):12-9. doi: 10.1016/j.canlet.2015.11.019. Epub 2015 Nov 18. PMID: 26604131. 15: Bellio C, DiGloria C, Spriggs DR, Foster R, Growdon WB, Rueda BR. The Metabolic Inhibitor CPI-613 Negates Treatment Enrichment of Ovarian Cancer Stem Cells. Cancers (Basel). 2019 Oct 29;11(11):1678. doi: 10.3390/cancers11111678. PMID: 31671803; PMCID: PMC6896080. 16: Koncošová M, Vrzáčková N, Křížová I, Tomášová P, Rimpelová S, Dvořák A, Vítek L, Rumlová M, Ruml T, Zelenka J. Inhibition of Mitochondrial Metabolism Leads to Selective Eradication of Cells Adapted to Acidic Microenvironment. Int J Mol Sci. 2021 Oct 6;22(19):10790. doi: 10.3390/ijms221910790. PMID: 34639130; PMCID: PMC8509312. 17: Smith ER, Hewitson TD. TGF-β1 is a regulator of the pyruvate dehydrogenase complex in fibroblasts. Sci Rep. 2020 Oct 21;10(1):17914. doi: 10.1038/s41598-020-74919-8. PMID: 33087819; PMCID: PMC7578649. 18: Kumstel S, Schreiber T, Goldstein L, Stenzel J, Lindner T, Joksch M, Zhang X, Wendt EHU, Schönrogge M, Krause B, Vollmar B, Zechner D. Targeting pancreatic cancer with combinatorial treatment of CPI-613 and inhibitors of lactate metabolism. PLoS One. 2022 Apr 22;17(4):e0266601. doi: 10.1371/journal.pone.0266601. PMID: 35452495; PMCID: PMC9032382. 19: Inoue J, Kishikawa M, Tsuda H, Nakajima Y, Asakage T, Inazawa J. Identification of PDHX as a metabolic target for esophageal squamous cell carcinoma. Cancer Sci. 2021 Jul;112(7):2792-2802. doi: 10.1111/cas.14938. Epub 2021 May 24. PMID: 33964039; PMCID: PMC8253269. 20: Li Y, Zhao Z, Liu H, Fetse JP, Jain A, Lin CY, Cheng K. Development of a Tumor-Responsive Nanopolyplex Targeting Pancreatic Cancer Cells and Stroma. ACS Appl Mater Interfaces. 2019 Dec 11;11(49):45390-45403. doi: 10.1021/acsami.9b15116. Epub 2019 Nov 26. PMID: 31769963; PMCID: PMC7372733.