Caspase Inhibitor

Z-VAD-FMK is a pan-caspase inhibitor and also an ICE-like protease inhibitor, which inhibits apoptosis by preventing the processing of CPP32 to its active form. Z-VAD-FMK sensitivity varies primarily due to differential expression of receptor-interacting protein 1 (RIP1). Z-VAD-FMK limits the cryopreservation-induced apoptosis by reducing caspase-3 activity of in vitro produced bovine embryos. Z-VAD-FMK is immunosuppressive in vitro and inhibits T cell proliferation without blocking the processing of caspase-8 and caspase-3. Z-VAD-FMK leads to a decrease in intracellular glutathione (GSH) with a concomitant increase in reactive oxygen species (ROS) levels in activated T cells. Z-VAD-FMK is due to oxidative stress via the depletion of GSH. Z-VAD-FMK can be used for the study of acute pancreatitis.

Q-VD-OPh is an irreversible pan-caspase inhibitor with potent antiapoptotic properties; inhibits caspase 7 with an IC₅₀ of 48 nM and 25-400 nM for other caspases including caspase 1, 3, 8, 9, 10, and 12. Q-VD-OPh can inhibits HIV infection. Q-VD-OPh is able to cross the blood-brain barrier.

Sulforaphane is an orally active inducer of the Keap1/Nrf2/ARE pathway. Sulforaphane promotes the transcription of tumor-suppressing proteins and effectively inhibits the activity of HDACs. Through the activation of the Keap1/Nrf2/ARE pathway and further induction of HO-1 expression, Sulforaphane protects the heart. Sulforaphane suppresses high glucose-induced pancreatic cancer through AMPK-dependent signal transmission. Sulforaphane exhibits both anticancer and anti-inflammatory properties.

Belnacasan (VX-765) is an orally bioactive proagent of VRT-043198, which is a potent and selective inhibitor of IL-converting enzyme (ICE)/caspase-1 with K_is of 0.8 nM and less than 0.6 nM for caspase-1 and caspase-4, respectively. Belnacasan (VX-765) inhibits the release of LPS-induced IL-1β and IL-18 by human PBMCs with an IC₅₀ of ~0.7 μM.

Caspase-4-IN-1 (compound 35) is a selective allosteric caspase-4 inhibitor that spares caspase-1, and in embodiments acts as a dual caspase-4/5 inhibitor.

Tauroursodeoxycholate (Tauroursodeoxycholic acid) is an orally active endoplasmic reticulum (ER) stress inhibitor. Tauroursodeoxycholate significantly reduces expression of apoptosis molecules, such as caspase-3 and caspase-12. Tauroursodeoxycholate also inhibits ERK.

Z-VAD(OMe)-FMK (Z-Val-Ala-Asp(OMe)-FMK) is a cell-permeable and irreversible pan-caspase inhibitor. Z-VAD(OMe)-FMK is an ubiquitin carboxy-terminal hydrolase L1 (UCHL1) inhibitor. Z-VAD(OMe)-FMK irreversibly modifies UCHL1 by targeting the active site of UCHL1.

Necrosulfonamide is a MLKL and Gasdermin D (GSDMD) inhibitor, capable of separately inhibiting necroptosis and pyroptosis of cells. Necrosulfonamide does not affect the activation of upstream signals, but specifically inhibits the downstream executor oligomerization step. Necrosulfonamide reduces the expression of the key kinases NLRP3 and caspase-1 involved in necroptosis and pyroptosis, activate the Nrf2 pathway and the downstream antioxidant enzymes, and also downregulates a variety of inflammatory factors. Necrosulfonamide plays significant roles in various diseases such as neurodegenerative diseases (such as Parkinson’s disease), tissue damage and ischemia-reperfusion injury, inflammatory bowel disease, osteoarthritis and fracture repair, and hair loss by regulating two important programmed necrosis pathways.

Z-DEVD-FMK is a specific and irreversible caspase-3 inhibitor with an IC₅₀ of 18 μM.

Emricasan (PF 03491390) is an orally active and irreversible pan-caspase inhibitor. Emricasan inhibits Zika virus (ZIKV)-induced increases in caspase-3 activity and protected human cortical neural progenitors.

Z-IETD-FMK (Z-IE(OMe)TD(OMe)-FMK) is a selective and cell permeable caspase-8 inhibitor. Z-IETD-FMK is also a granzyme B inhibitor.

Ac-YVAD-cmk (Caspase-1 Inhibitor II) is a selective caspase-1 (IL-1beta converting enzyme, ICE)) inhibitor with neuroprotective and anti-inflammatory effects. Ac-YVAD-cmk effectively suppresses the expression of IL-1β and IL-18. Ac-YVAD-cmk inhibits pyroptosis in many diseases.

Glycochenodeoxycholic acid (Chenodeoxycholylglycine) is a relatively toxic bile salt generated in the liver from chenodeoxycholic acid and glycine. Glycochenodeoxycholic acid inhibits Autophagosome formation and impairs lysosomal function by inhibiting lysosomal proteolysis and increasing lysosomal pH in human normal liver cells, leading to the Apoptosis of human hepatocyte cells. Glycochenodeoxycholic acid induces stemness and chemoresistance via activating STAT3 signaling pathway in hepatocellular carcinoma cells (HCC). Glycochenodeoxycholic acid is promising for research in the field of cholestasis desease, hepatocellular carcinoma and primary sclerosing cholangitis (PSC).

Tauroursodeoxycholate (Tauroursodeoxycholic acid; TUDCA) sodium is an endoplasmic reticulum (ER) stress inhibitor. Tauroursodeoxycholate significantly reduces expression of apoptosis molecules, such as caspase-3 and caspase-12. Tauroursodeoxycholate also inhibits ERK.

Z-VAD is an irreversible, broad-spectrum pan-caspase inhibitor that can inhibit a variety of caspases including caspase-3, -6, -7, -8, -9, etc. (with a weaker inhibitory effect on caspase-2). Z-VAD can block apoptosis signaling pathways, induce autophagy and necrosis in tumor cells, and has anti-angiogenic activity. Z-VAD can enhance the sensitivity of breast cancer and lung cancer cells to radiotherapy in vitro and in vivo, and prolong the growth delay of tumor xenograft models. Z-VAD is well tolerated and is mainly used in research related to cancer radiosensitization and cell death pathway regulation.

(-)-Isoproterenol (Levisoprenalinel) hydrochloride is the R-isomer of Isoproterenol. (-)-Isoproterenol hydrochloride can reduce the cleavage of caspase 3 and TNFα levels in retinal endothelial cells (REC). (-)-Isoproterenol hydrochloride can be used for the study of diabetic retinopathy.

Ac-DEVD-CHO is a Caspase-3 inhibitor with a K_i value of 230 pM.

Berberine sulfate is an alkaloid isolated from the Chinese herbal medicine Huanglian, as an antibiotic. Berberine sulfate induces reactive oxygen species (ROS) generation and inhibits DNA topoisomerase. Berberine sulfate has antineoplastic properties. The sulfate form improves bioavailability.

Crustecdysone (20-Hydroxyecdysone) is a naturally occurring ecdysteroid hormone isolated from Serratula coronata which controls the ecdysis (moulting) and metamorphosis of arthropods, it inhibits caspase activity and induces autophagy via the 20E nuclear receptor complex, EcR-USP. Crustecdysone exhibits regulatory or protective roles in the cardiovascular system. Crustecdysone is an active metabolite of Ecdysone (HY-N0179).

Inclisiran sodium is a double-stranded small interfering RNA (siRNA) molecule. Inclisiran sodium inhibits the transcription of PCSK9. Inclisiran sodium inhibits Pyroptosis, activates PPARγ, and reduces NLRP3, cleaved caspase-1, IL-1β, and IL-18. Inclisiran sodium has anti-inflammatory, lipid-regulating and anti-atherosclerotic activities. Inclisiran sodium can be used in researches of hyperlipidemia and cardiovascular disease (CVD).