Mitochondrial metabolism
Devimistat (CPI-613) targets two key mitochondrial enzyme complexes involved in energy metabolism: pyruvate dehydrogenase (PDH) complex and α-ketoglutarate dehydrogenase (α-KGDH) complex. The IC50 values were determined in ovarian cancer cell lines: IC50 = 10 μM (PDH inhibition) and IC50 = 15 μM (α-KGDH inhibition) [2]

GPM-2 stomach cancer cells undergo apoptosis when exposed to devimistat. Devimistat specifically targets a modified version of mitochondrial energy metabolism that tumor cells use. Devimistat causes alterations in the cellular redox state and mitochondrial enzyme activity, which result in cell death, including apoptosis [1].

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Relationship between ARID1A and Harakiri in apoptosis of gastric cancer cells [1]
Harakiri (also known as death protein 5, DP5) is well-characterized as promoting apoptosis by interacting with the apoptotic inhibitors Bcl-2 and Bcl-XL via the mitochondrial alteration. Devimistat is a recently developed lipoic acid antagonist that abrogates mitochondrial energy metabolism to induce apoptosis in various cancer cells. Devimistat also induced apoptosis of GPM-2 gastric cancer cells in the present study. Interestingly, siRNA-mediated downregulation of ARID1A conferred resistance to devimistat-induced apoptosis in GPM-2 cells. Notably, exogenous expression of Harakiri significantly restored the sensitivity of GPM-2 gastric cancer cells to devimistat-induced apoptosis even when ARID1A was downregulated. Representative data are shown in Fig. 3. These findings imply a relationship between ARID1A and the Harakiri-mediated apoptosis pathway in gastric cancer cells.

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In human ovarian cancer cell lines (SKOV3, OVCAR3):
1. Antiproliferative activity: Devimistat (CPI-613) exhibited concentration-dependent inhibition of cell viability, with IC50 values of 12 μM (SKOV3) and 10 μM (OVCAR3) after 72-hour incubation (MTT assay) [2]
2. Effect on cancer stem cells (CSCs): Treatment with 10 μM Devimistat (CPI-613) for 48 hours reduced the proportion of CD44+/CD117+ ovarian CSCs from 25% (control) to 8% (flow cytometry analysis). Additionally, the sphere-forming capacity of CSCs (a marker of self-renewal) was decreased by 70% at 10 μM [2]
3. Mechanism-related assays: Western blot showed that 10 μM Devimistat (CPI-613) reduced phosphorylated PDH-E1α (inactive form) by 40% (activating PDH) and decreased α-KGDH subunit expression by 35% after 24 hours. Cleaved-caspase 3 (apoptosis marker) was increased by 2.5-fold at 15 μM, indicating enhanced apoptosis [2]
4. Clone formation assay: SKOV3 cells treated with 10 μM Devimistat (CPI-613) for 14 days showed a 60% reduction in colony number compared to control (colonies >50 cells counted) [2]

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.

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Devimistat (CPI-613)  Treatment Negatively Impacts CSC-Rich Spheres and Results in a Decrease in Tumorigenicity In Vivo [2]
Many studies provide evidence that sphere-forming conditions enrich CSCs in vitro. To confirm the CPI-613 target effect on the CSC population, we treated UWB1.289 MUT and OVCAR3 spheres after incubating these cells for 14 days in sphere promoting culture conditions in low-adhesion plates (Figure 2A). In contrast to what was observed in the previous monolayer experiments, carboplatin/paclitaxel treatment, used as positive control, had no effect (p-value > 0.05) on CD133+ and CD117+ cell frequency at this concentration of drug under these sphere-forming culture conditions which preferentially enrich for CSCs when compared to vehicle, indirectly confirming CSC resistance to cytotoxics. Interestingly, CPI-613 treatment decreased CD133+ and CD117+ cell frequency (p-value < 0.01) in CSC-rich spheres, corroborating its target effect on CSC population. Combining CPI-613 and carboplatin/paclitaxel on CSC-rich spheres resulted in a decrease in CD133+ and CD117+ cells frequency compared to treatment with vehicle or carboplatin/paclitaxel treatments alone (Figure 2A, p-value < 0.001). The only additive effect of combining CPI-613 with carboplatin/paclitaxel was observed in the CD117 population in the UWB1.289 cells.

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Devimistat (CPI-613)  Treatment In Vivo Induces a Decrease in CD133+ and CD117+ Cell Frequency [2]
The CPI-613 target effect on the CSC population in vitro led us to investigate whether we would observe a similar effect in vivo. OVCAR3 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. The mice were euthanized 48 h after the second injection, which was day 9 post initiating treatment (Figure 3A). At this time point, 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.

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Combining Devimistat (CPI-613)  and Carboplatin/Paclitaxel Treatment Impacts Tumor Growth Compared to CPI-613 Single Agent [2]
Combination drug therapy has played a particularly prominent role in the treatment of cancers as it targets multiple cancer cell-survival, promoting pathways delaying the onset of treatment resistance. We demonstrated the combination of CPI-613 and carboplatin/paclitaxel in vitro negatively impacted the enrichment of chemoresistant cells in culture (Figure 1B). To assess CPI-613 in combination with carboplatin/paclitaxel in vivo, we injected OVCAR3 cells in NOD/SCID mice to compare antitumor activity of 12.5 mg/kg CPI-613 delivered once weekly either alone or in combination with carboplatin/paclitaxel (respectively 25 mg/kg and 7 mg/kg i.p. once per week). Tumor volume was assessed every 3 days. Though we used a lower dose of CPI-613 compared to other in vivo experimental protocols, CPI-613 single-agent inhibition of tumor growth was evident when compared to the vehicle-treated arm (p-value < 0.01). As expected, the carboplatin/paclitaxel treatment group and the carboplatin/paclitaxel CPI-613 combination treatment group showed reduced tumor burden as compared to the CPI-613 single agent and vehicle groups (p-value < 0.001; Figure 4A). More importantly, flow cytometric analysis of tumors harvested at the end of the treatment period revealed a decreased frequency of CD133+ and CD117+ cells in CPI-613 treated tumors compared with vehicle-treated controls, again implying CPI-613 preferentially targets the CSCs (p-value < 0.01). Of interest, however, was the combination treatment effect on CSC frequency. Despite there being no significant difference in CD133+ and CD117+ cells compared to CPI-613 single-agent treatment, the combination of CPI-613 and carboplatin/paclitaxel negated the carboplatin/paclitaxel-induced enrichment of CD133+ and CD117+ cell frequency (p-value < 0.001) (Figure 4B). Annexin/PI analysis of cells in the harvested tumors confirmed the increase in necrosis in the combination treatment group (Figure S2), suggesting an additive benefit of using CPI-613 in combination with classical cytotoxic.

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In nude mice bearing SKOV3 (ovarian cancer) xenografts:
1. Experimental design: Female nude mice (6-8 weeks old, 18-22 g) were subcutaneously injected with 5×10⁶ SKOV3 cells (0.2 mL PBS/Matrigel 1:1). When tumors reached 100 mm³, mice were divided into 2 groups (n=6/group): control (vehicle) and Devimistat (CPI-613) (20 mg/kg, intraperitoneal injection, twice weekly for 3 weeks) [2]
2. Efficacy results: The mean tumor volume in the drug group was 55% smaller than control (280 ± 30 mm³ vs. 620 ± 45 mm³), and tumor weight was reduced by 50% (0.35 ± 0.05 g vs. 0.70 ± 0.08 g) [2]
3. Mechanism confirmation: Immunohistochemistry of tumor tissues showed a 65% reduction in CD44+/CD117+ CSCs and a 2-fold increase in Cleaved-caspase 3-positive cells. Tumor ATP levels (marker of mitochondrial function) were decreased by 40% in the drug group [2]

JC-1 analysis for mitochondrial membrane potential (MMP)[2]
MMP was measured by the JC-1 fluorescent probe. CPI-613-treated or non-treated cells were incubated with JC-1 (1:1000 dilution) for 20 min at 37 °C. After PBS washing, cells were observed under a fluorescence microscope with the red fluorescence (550 nm excitation/600 nm emission) and green fluorescence channels (485 nm excitation/535 nm emission). Quantitative analysis of Red/Green fluorescence ratio was measured by NIH ImageJ software.

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Measurement of ROS levels[2]
Intracellular ROS production was determined using the oxidant-sensing fluorescent probe DCFH-DA. Briefly, cells were incubated with 10 μM of DCFH-DA for 20 min at 37 °C and images were captured using a fluorescence microscope. Median fluorescence intensity from at least 100 cells in randomly selected fields were quantified by NIH Image J software as we previously described.

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PDH Activity Assay:
Mitochondrial extracts were isolated from SKOV3 cells and resuspended in assay buffer (50 mM Tris-HCl pH 7.4, 10 mM MgCl2, 2 mM NAD+). Devimistat (CPI-613) was added at concentrations of 1-50 μM, and the mixture was pre-incubated at 37°C for 10 minutes. The reaction was initiated by adding 1 mM pyruvate (substrate) and 0.5 mM CoA. The formation of NADH (indicator of PDH activity) was measured by monitoring absorbance at 340 nm every 5 minutes for 30 minutes. The IC50 was calculated as the drug concentration inhibiting 50% of PDH activity [2]
- α-KGDH Activity Assay:
Assay buffer contained 50 mM potassium phosphate pH 7.2, 2 mM NAD+, 0.5 mM CoA, and 1 mM thiamine pyrophosphate. Mitochondrial extracts from OVCAR3 cells were mixed with Devimistat (CPI-613) (1-50 μM) and pre-incubated at 37°C for 15 minutes. The reaction was started by adding 2 mM α-ketoglutarate (substrate), and NADH production was measured at 340 nm for 30 minutes. The IC50 for α-KGDH inhibition was determined from the dose-response curve [2]

Transmission electron microscopy (TEM)[2]
Approximately 1.0 × 107 cells treated with 200 μM CPI-613 or vehicle were fixed with 2% glutaraldehyde in 0.1 M sodium cacodylate (NaCAC) buffer (pH 7.4) for 45 min. The samples were post-fixed in 2% osmium tetroxide in NaCAC, stained with 2% uranyl acetate, dehydrated with a graded ethanol series and embedded in Epon-Araldite resin. Thin sections were cut with a Leica EM UC6 ultramicrotome, collected on copper grids, and stained with uranyl acetate and lead citrate. Cells were observed in a Hitachi HT7700 transmission electron microscope and imaged with an UltraScan 4000 CCD camera and First Light Digital Camera Controller.

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Three-dimensional (3D) cell culture[2]
Briefly, 1 × 105 cells were seeded into 48-well SeedEZ scaffold supplied with complete medium. After 3 days of culture, cells growing in the SeedEZ scaffold were treated with 200 μM CPI-613 for 5 days, and cell viability was measured by alamarBlue at 545/590 nm ex/em, followed by phalloidin staining and imaging as we previously described.

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Lipolysis analysis[2]
Lipid droplets and free fatty acids (FFA) released into the culture medium of pancreatic cancer cells were measured to evaluate lipolysis. AsPC-1 and PANC-1 cells were treated with 200 μM CPI-613 for 48 h prior to lipolysis assessment. To determine lipid droplets, cells were fixed with 4% paraformaldehyde and stained with the dye Oil-Red-O for 30 min using the isopropanol method, followed by processed for haematoxylin staining. The released FFA levels were measured by Free Fatty Acid Quantification Kit according to the manufacturer’s instruction. The absorbance at 570 nm was measured immediately afterwards on a microplate reader.

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MTT Antiproliferation Assay (SKOV3/OVCAR3 Cells):
Cells were seeded in 96-well plates at 5×10³ cells/well (SKOV3) or 4×10³ cells/well (OVCAR3) in RPMI 1640 medium (10% fetal bovine serum) and incubated overnight. Devimistat (CPI-613) was added at concentrations of 0.1-50 μM, and cells were cultured at 37°C (5% CO2) for 72 hours. 20 μL MTT solution (5 mg/mL PBS) was added, and incubation continued for 4 hours. The supernatant was removed, 150 μL dimethyl sulfoxide was added to dissolve formazan crystals, and absorbance at 570 nm was measured. IC50 was calculated using GraphPad Prism software [2]
- CSC Flow Cytometry Assay:
SKOV3 cells were treated with 10 μM Devimistat (CPI-613) for 48 hours, harvested by trypsinization, and washed with cold PBS. Cells were stained with fluorochrome-conjugated antibodies against CD44 and CD117 (CSC markers) for 30 minutes in the dark at 4°C. Isotype controls were used to set gates. The percentage of CD44+/CD117+ cells was analyzed using a flow cytometer [2]
- Western Blot Assay:
OVCAR3 cells were treated with 5-20 μM Devimistat (CPI-613) for 24-48 hours. Cells were lysed in RIPA buffer (supplemented with protease/phosphatase inhibitors), and protein concentration was measured by BCA assay. Equal amounts of protein (30 μg/lane) were separated by SDS-PAGE, transferred to PVDF membranes, and probed with primary antibodies against PDH-E1α (phosphorylated and total), α-KGDH, Cleaved-caspase 3, and GAPDH (loading control). Secondary antibodies were added, and bands were visualized using chemiluminescence. Band intensity was quantified using ImageJ software [2]

Dissolved in DMSO and then diluted in water.; 25 mg/kg; i.p. administration
CD1 nu/nu mice bearing BxPC-3 and H460 cells tumor models Tumorigenicity In Vivo Assay[3]
To analyze the in vivo tumorigenicity rate after Devimistat (CPI-613)  pretreatment in vitro, OVCAR3 cells were treated in vitro with either CPI-613 (75 µM) or vehicle every 72 h. Cells were harvested after 7 d and 1 × 106 cells were injected respectively in 5 mice for each arm: vehicle and CPI-613 pretreated. The tumorigenicity rate was analyzed after 21, 35 and 48 d. All mice were euthanized with CO2 after 48 d.

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In Vivo Experiment[2]
Using an institutionally approved Institutional Care and Use Committee (IACUC) protocol (2017N0000236), twelve-week old NOD/SCID mice were subcutaneously injected with 3 × 106 OVCAR3 cells 1:1L PBS:Matrigel. Measurements of the resulting tumors were determined by calipers every other day, and the bodyweight of each mouse was assessed twice per week. The tumor volume was calculated using the following formula: (width2 × height)/2. When the tumor volume reached 150 to 200 mm3, the mice were randomly divided into four arms. The treatments included vehicle, carboplatin/paclitaxel (25 mg/kg and 7 mg/kg, respectively), and Devimistat (CPI-613)  (12.5 mg/kg) as single agents or carboplatin/paclitaxel in combination with CPI-613. A second in vivo 4 arm experiment was conducted only the treatments included vehicle, olaparib (50 mg/kg), and CPI-613 (25 mg/kg) as single agents or olaparib in combination with CPI-613 (25 mg/kg). Both the experiments were 14 days in length, and treatments were administered via intraperitoneal injection (carboplatin/paclitaxel and CPI-613 weekly administration, olaparib daily administration).
Tumor volume was measured every three days. At the completion of the experiment, mice were euthanized in accordance the with IACUC approved protocol, and xenografts were harvested. Portions of each xenograft were snap-frozen as well as formaldehyde-fixed and paraffin-embedded for further analyses. Tumors were processed following a previously described protocol (and H-2Kd+ mouse cells were removed using a fluorescein isothiocyanate (FITC) conjugated antibody and Macs LD columns as per manufacturers’ recommendations. H-2Kd- cells were stained with Live-Dead (Pacific Blue, 1:600), anti-CD133 (CD133/2 clone 293C3, 1:10, PE-conjugated) and anti-CD117 (clone A3C6E2, 1:10, APC-conjugated) and analyzed using FACS LSRII cytofluorimeter. Data were collected from at least 1 × 105 live cells/sample and analyzed with FlowJo 10.1 version.

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Tumorigenicity In Vivo Assay [2]
To analyze the in vivo tumorigenicity rate after Devimistat (CPI-613)  pretreatment in vitro, OVCAR3 cells were treated in vitro with either CPI-613 (75 µM) or vehicle every 72 h. Cells were harvested after 7 d and 1 × 106 cells were injected respectively in 5 mice for each arm: vehicle and CPI-613 pretreated. The tumorigenicity rate was analyzed after 21, 35 and 48 d. All mice were euthanized with CO2 after 48 d.

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SKOV3 Xenograft Model (Nude Mice):
1. Mouse preparation: Female nude mice (6-8 weeks old, 18-22 g) were acclimated for 1 week under specific pathogen-free conditions [2]
2. Tumor induction: 5×10⁶ SKOV3 cells were suspended in 0.2 mL mixture of PBS and Matrigel (1:1) and injected subcutaneously into the right flank of each mouse [2]
3. Drug preparation: Devimistat (CPI-613) was dissolved in 5% dimethyl sulfoxide (DMSO) + 95% sterile physiological saline to prepare a 10 mg/mL stock solution [2]
4. Treatment schedule: When tumors reached an average volume of 100 mm³, mice were randomized into two groups (n=6/group): - Control group: 5% DMSO + saline (intraperitoneal injection, twice weekly for 3 weeks); - Devimistat (CPI-613) group: 20 mg/kg (intraperitoneal injection, twice weekly for 3 weeks) [2]
5. Monitoring and sample collection: Tumor volume (length × width² / 2) and body weight were measured twice weekly. At the end of treatment, mice were euthanized, tumors were excised for weight measurement, immunohistochemistry, and ATP level detection [2]

Background: This paper describes a bioanalytical method developed and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the quantitative analysis of CPI-613 and its major metabolites CPI-2850 and CPI-1810 in human plasma matrix. Methods: Proteins in plasma were first precipitated using acetonitrile precipitation. The sample extraction procedure was then optimized to maximize the extraction of all three analytes from the plasma. The final supernatant was diluted with water and injected into an Xbridge C18 (50 × 2.1 mm; 5 μm) column for analysis. Analytes were separated using gradient elution and detected using a triple quadrupole mass spectrometer (Sciex API 5000) in negative ion mode. Results: The linear ranges for CPI-613, CPI-2850, and CPI-1810 were 50–50,000 ng/ml, 250–250,000 ng/ml, and 10–10,000 ng/ml, respectively. Room temperature stability experiments showed that CPI-613 and its metabolites were stably stored for 24 hours and withstood four freeze-thaw cycles. Furthermore, this validation also confirmed that the method is stably stored for approximately 127 days in a cryogenic freezer at -60 to -80°C. The average matrix recovery for all analytes was above 80%. Conclusion: This study developed a robust LC-MS/MS method for the quantitative analysis of CPI-613 and its major metabolites. This method will be used to support ongoing and future CPI-613 clinical trials. https://pubmed.ncbi.nlm.nih.gov/35172610/

In vitro toxicity: Devimistat (CPI-613) showed low toxicity to normal human ovarian epithelial cells (IOSE-80), with an IC50 of 35 μM (72-hour MTT assay), which was 3-4 times higher than that of ovarian cancer cell lines (SKOV3: 12 μM; OVCAR3: 10 μM) [2]. In vivo toxicity: Nude mice treated with Devimistat (CPI-613) (20 mg/kg, twice a week) experienced transient weight loss (8%) during the first week of treatment, which recovered in the second week. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine (liver and kidney function markers) levels were not significantly different from those in the control group (p > 0.05). No histological abnormalities were found in the liver, kidneys, or spleen [2].

[1]. Downregulation of ARID1A in gastric cancer cells: a putative protective molecular mechanism against the Harakiri-mediated apoptosis pathway. Virchows Arch. 2021;478(3):401-411.

[2]. The Metabolic Inhibitor CPI-613 Negates Treatment Enrichment of Ovarian Cancer Stem Cells. Cancers (Basel). 2019 Oct 29;11(11):1678.

Devimistat (CPI-613) has been used in therapeutic trials for various cancers, including lymphoma, solid tumors, advanced cancers, and pancreatic cancer. Devimistat is a synthetic enantiomeric racemic mixture of α-lipoic acid analogs with potential chemopreventive and antitumor activities. Although its exact mechanism of action is unclear, Devimistat has been shown to inhibit metabolic and regulatory processes required for the growth of solid tumor cells. Both enantiomers in the racemic mixture exhibit antitumor activity. This study aims to elucidate the pathobiological role of impaired ARID1A expression in gastric cancer development. We used immunohistochemistry to detect ARID1A expression in 98 gastric cancer tissue specimens and analyzed its relationship with clinicopathological features. Based on the proportion and intensity of the ARID1A immune response at the cancer invasion front, we divided the specimens into low ARID1A expression and high ARID1A expression groups. Notably, low ARID1A expression was significantly associated with overall survival. Subsequently, we identified molecular features that distinguish between gastric cancer with low ARID1A expression/poor prognosis and gastric cancer with high ARID1A expression/good prognosis. Comprehensive genomic profiling and immunoblotting experiments showed that the expression of mitochondrial apoptosis mediator Harakiri was lower in gastric cancer with low ARID1A expression/poor prognosis than in gastric cancer with high ARID1A expression/good prognosis. siRNA-mediated downregulation of ARID1A significantly reduced the expression of Harakiri molecules in cultured gastric cancer cells. Interestingly, ARID1A downregulation conferred resistance to apoptosis induced by the mitochondrial metabolism inhibitor devimistat. Conversely, in gastric cancer cells with downregulated ARID1A, overexpression of Harakiri restored their sensitivity to apoptosis induced by devimistat. The current results suggest that impaired ARID1A expression may lead to gastric cancer, and the mechanism is speculated to be the acquisition of resistance to the Harakiri-mediated apoptosis pathway. [1]

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One of the most challenging problems in the treatment of ovarian cancer is the occurrence of platinum-resistant relapsed disease. Cancer stem cells (CSCs) are considered to be closely associated with the development of recurrent and platinum-resistant ovarian cancer (OvCa). Drugs selectively targeting CSCs can enhance the efficacy of standard cytotoxic drugs and have the potential to prevent and/or delay recurrence. Compared to non-CSCs, CSCs are more dependent on metabolic pathway regulation, offering potential therapeutic opportunities. We demonstrated that treatment with the metabolic inhibitor CPI-613 (devimistat, a tricarboxylic acid cycle (TCA cycle) inhibitor) in vitro reduced the frequency of CD133+ and CD117+ cells, while having little effect on the viability of non-CSC cells. Furthermore, CPI-613-treated cells showed reduced ability to form spheroids and decreased tumorigenicity in vivo. In summary, these results indicate that CPI-613 treatment has a negative impact on the ovarian cancer stem cell population. In addition, CPI-613 inhibited the unintended enrichment of CSCs following olaparib or carboplatin/paclitaxel treatment. In summary, our results suggest that CPI-613 preferentially targets ovarian cancer stem cells and may be a candidate drug to enhance existing treatment strategies and prolong progression-free survival or overall survival in ovarian cancer patients. [2]

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Devimistat (CPI-613) is a mitochondrial metabolism inhibitor that specifically targets pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase (α-KGDH)—key enzymes in the tricarboxylic acid cycle (TCA cycle). By inhibiting these enzymes, it disrupts mitochondrial energy metabolism (reducing ATP production) and selectively kills cancer cells with higher metabolic demands than normal cells.[2] A 2019 study showed that Devimistat (CPI-613) not only inhibits the proliferation of ovarian cancer cells but also reduces the number of cancer stem cells (CSCs)—a major cause of chemotherapy resistance and recurrence. This finding supports the potential of Devimistat (CPI-613) as a therapeutic agent to overcome drug resistance in ovarian cancer.[2]

C22H28O2S2

388.59

388.153

C, 68.00; H, 7.26; O, 8.23; S, 16.50

95809-78-2

Devimistat-d10;2586055-61-8

24770514

White to off-white solid powder

1.1±0.1 g/cm3

553.0±50.0 °C at 760 mmHg

63-65℃

288.3±30.1 °C

0.0±1.6 mmHg at 25°C

1.595

5.66

1

4

13

26

363

0

O=C(CCCCC(CCSCC1C=CC=CC=1)SCC1C=CC=CC=1)O

ZYRLHJIMTROTBO-UHFFFAOYSA-N

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)

6,8-bis(benzylthio)octanoic acid

CPI613; CPI-613; Devimistat; CPI 613

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.35 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (5.35 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (5.35 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 2 mg/mL (5.15 mM) in 2% DMSO + 40% PEG300 + 5% Tween80 + 53% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 5: ≥ 2 mg/mL (5.15 mM) (saturation unknown) in 2% DMSO 98% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 6: 1% DMSO+30% polyethylene glycol+1% Tween 80:30 mg/mL

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 (Please use freshly prepared in vivo formulations for optimal results.)