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Emricasan is an irreversible pan-caspase inhibitor. A key small molecule component of the published CEPT cocktail, enhances cell survival, clonogenicity, and cytoprotection of hPSCs.
Emricasan is a potent caspase inhibitor, demonstrating irreversible inhibition and a significant first-pass effect2. Emricasan acts in synergy with Chroman 1, a potent and selective ROCK inhibitor to improve survival of human pluripotent stem cells (hPSCs). The combination of Chroman 1 and Emricasan was found to be superior and improving cell survival and viability than using either Chroman 1 or Y27632 alone1.
Emricasan promotes survival of hPSCs in culture when used in combination with Chroman 1, Trans-ISRIB and polyamines, a small molecule combination known as CEPT. When used as part of the CEPT cocktail, Emricasan’s synergistic effects improves single-cell clonogenicity and gene editing, EB and organoid formation, and survival of pluripotent and differentiated cells following cryopreservation1.
Emricasan has been found to directly improve hepatocytes phenotype in primary rat cirrhotic hepatocytes and has hepatoprotective effects in human liver cells3. Emricasan, formerly known as IDN-6556, in combination with birinapan, has been used to treat acute myeloid leukemia4.
Emricasan has been used in clinical trials for the treatment of non-alcoholic steatohepatitis (NASH) with advanced fibrosis (scarring) and cirrhosis. Emricasan has also been shown to inhibit Zika virus (ZIKV)-induced increases in caspase-3 activity and protect infected astrocytes from ZIKV-induced cell death. Emricasan preserves cell viability after infection with several strains of Zika5. Emricasan is a component of Captivate Bio's CET Cocktail.
Alternative names: PF 03491390; IDN-6556 Applications: Stem Cell Survival; DEPT Cocktail; Pluripotent Stem Cell Culture; Single-Cell Cloning; Gene Editing; Cryopreservation & Cell Banking; Tissue Engineering; Biomanufacturing; Regenerative Medicine; Zika virus; Influenza virus; NASH research Cell types: Pluripotent Stem Cells, iPSCs, ESCs
The data provided herein may relate to products or workflows that have not been fully validated by Captivate Bio and is subject to change without notice.
References and sample data are from publications that support the biological activity of the product. This data reference is from Chen et al. 2021 Nat Methods.
Figure 1. When the small molecule combination of Chroman 1 (50 nM) and Emricasan (5 µM) (C+E) was applied to hPSCs for the first 24 hours after single-cell dissociation, improved cells survival and a decreased number of apoptotic cells were seen, observed by a clear reduction in caspase activity.
Figure 2. Dissociated hPSC cultures supplemented with Emricasan and Chroman 1 (C+E), showed increased viability and cell survival compared to supplementation with a ROCK inhibitor alone.
Keywords: Emricasan, emricasan supplier, IDN6556, caspases, inhibitors, pluripotent stem cells, CEPT, cryopreservation, differentiation, zika, self-renewal, NASH, stem cell proliferation stem, cells, organoids, induced, pluripotent, ROCKI, ROCK1, ROCKII, ROCK2, proliferation, reprogramming, cryopreservation, differentiation, cell, freezing, media, cryogenesis, self-renewal, neural
When used to enhance hPSC survival and clonal expansion during passaging, Emricasan is used at a final concentration of 5 µM in cell culture media. Emricasan is generally added to culture media at passaging and is removed during the first feeding the following day, and is used in combination with synergistic small molecule compounds (Chroman 1 and Trans-ISRIB) and a polyamine solution, known as the CEPT cocktail, to improve survival of dissociated cells. See Chen et al. 2021 for more information on CEPT application and dosing for improved hPSC survival.
Yes. Emricasan (dosed at 5 µM for 24 hours at each passage in combination with Chroman 1) was shown to be safe for use in routine passaging of hPSCs dissociated as single cells. After application for 40 passages in culture, cells maintained normal karyotypes, expressed expected pluripotency markers, and were capable of multii-lineage differentiation through directed differentiation protocols and embryoid body formation. (Chen et al. Nature Methods 2021)
Emricasan is a clinical-stage drug, pan-caspase inhibitor. As part of the CEPT cocktail, Emricasam acts in synergy as a cytoprotectant for plurpotent stem cells under stress.
Emricasan is a potent and irriversible pan-caspase inhibitor. Emricasan acts in synergy with Chroman 1, a potent and selective ROCK inhibitor, to improve survival and viability of dissociated human pluripotent stem cells (hPSCs). When used in combination with Chroman 1, Trans-ISRIB, and polyamines (a combination known as CEPT), Emricasan’s synergistic effects improves single-cell clonogenicity and gene editing, EB and organoid formation, and survival of pluripotent and differentiated cells following cryopreservation. (Chen et al. Nature Methods 2021).
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This research spotlight highlights the superior cryoprotective capacity of the CEPT method and the survival and functionality of preserved hPSCs.
