2. Signaling Pathways
  3. Apoptosis
  4. Caspase

Caspase

Caspase

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Caspase is a family of cysteine proteases that play essential roles in apoptosis (programmed cell death), necrosis, and inflammation. There are two types of apoptotic caspases: initiator (apical) caspases and effector (executioner) caspases. Initiator caspases (e.g., CASP2, CASP8, CASP9, and CASP10) cleave inactive pro-forms of effector caspases, thereby activating them. Effector caspases (e.g., CASP3, CASP6, CASP7) in turn cleave other protein substrates within the cell, to trigger the apoptotic process. The initiation of this cascade reaction is regulated by caspase inhibitors. CASP4 and CASP5, which are overexpressed in some cases of vitiligo and associated autoimmune diseases caused by NALP1 variants, are not currently classified as initiator or effector in MeSH, because they are inflammatory enzymes that, in concert with CASP1, are involved in T-cell maturation.

Caspase Isoform Specific Products:

Caspase Isoform Comparison
Cat. No. Product Name Effect Purity Chemical Structure
  • HY-P1009
    Z-YVAD-FMK
    		Inhibitor ≥98.0%
    Z-YVAD-FMK is a cell-permeable caspase-1 and -4 inhibitor with anti-inflammatory and anti-tumor activities.
    Z-YVAD-FMK
  • HY-W004283
    Pentadecanoic acid
    		Activator 99.92%
    Pentadecylic acid is a saturated fatty acid with a 15-carbon backbone.
    Pentadecanoic acid
  • HY-P1008
    Z-VDVAD-FMK
    		Inhibitor ≥98.0%
    Z-VDVAD-FMK is a special inhibitor of caspase-2. Z-VDVAD-FMK produces a reduction in Lovastatin-induced apoptosis.
    Z-VDVAD-FMK
  • HY-W250111
    Carboxymethyl chitosan
    		Inhibitor
    Carboxymethyl chitosan is a derivative of chitosan. Carboxymethyl chitosan inhibits Apoptosis and ROS. Carboxymethyl chitosan increases the expression of Bcl-2 and reduces the expression of Bax, cytochrome c and caspase-3. Carboxymethyl chitosan inhibits the migration of various cells. Carboxymethyl chitosan exerts antitumor effects on Lewis tumors and hepatocarcinoma.
    Carboxymethyl chitosan
  • HY-B0257
    Levonorgestrel
    		Activator 99.98%
    Levonorgestrel is an orally active inhibitor of progesterone (HY-N0437). Levonorgestrel has anticancer activity and can induce Apoptosis. Levonorgestrel can be used as a contraceptive and in combination with other medications. Levonorgestrel can be used in the study of osteoporosis and uterine leiomyoma.
    Levonorgestrel
  • HY-18705
    Azoramide
    		Inhibitor 99.57%
    Azoramide is a potent, orally active small-molecule modulator of the unfolded protein response (UPR). Azoramide improves ER protein folding and elevates ER chaperone capacity, which together protects cells against ER stress. Azoramide alleviates PLA2G6 mutant-induced ER stress through modulating unfolded protein response, and enhances the CERB signaling to rescue mitochondrial function, thereby preventing apoptosis of DA neurons. Azoramide has antidiabetic activity.
    Azoramide
  • HY-111675
    Ac-FLTD-CMK
    		Inhibitor 99.18%
    Ac-FLTD-CMK, a gasdermin D (GSDMD)-derived inhibitor, is a specific inflammatory caspases inhibitor. Ac-FLTD-CMK is effective against caspases-1 (IC50 of 46.7 nM), caspases-4 (IC50 of 1.49 μM), caspases-5 (IC50 of 329 nM), and caspases-11 , but not the apoptotic caspases such as caspase-3.
    Ac-FLTD-CMK
  • HY-145757
    Elevenostat
    		Inducer
    Elevenostat (JB3-22) is a selective HDAC11 inhibitor with an IC50 of 0.235 µM. Elevenostat can induce apoptosis of multiple myeloma cells and has anti-tumor effect. In addition, Elevenostat inhibits the maturation of mouse oocytes.
    Elevenostat
  • HY-X0009
    Tambiciclib
    		Activator 99.21%
    Tambiciclib (GFH009, JSH-009) is an orally active, highly potent and selective CDK9 inhibitor (IC50 = 1 nM), demonstrating >200-fold selectivity over other CDKs, >100-fold selectivity over DYRK1A/B, and excellent selectivity over 468 kinases/mutants. Tambiciclib demonstrates potent in vitro and in vivo antileukemic efficacy in acute myeloid leukemia (AML) mouse models by inhibiting RNA Pol II phosphorylation, downregulating MCL1 and MYC, and inducing apoptosis. Tambiciclib can be used for AML research.
    Tambiciclib
  • HY-13229
    BOC-D-FMK
    		Inhibitor
    Boc-D-FMK is a cell-permeable, irreversible and broad spectrum caspase inhibitor. Boc-D-FMK inhibits apoptosis stimulated by TNF-α with an IC50 of 39 μM.
    BOC-D-FMK
  • HY-13560
    AVN-944
    		Activator 99.89%
    AVN-944 (VX-944) is an orally active, potent, selective, noncompetitive and specific inhibitor of IMPDH (inosine monophosphate dehydrogenase). AVN-944 is an essential rate-limiting enzyme in de novo guanine nucleotide synthesis. AVN-944 is also an inhibitor of arenavirus RNA synthesis, and blocks arenavirus infection. AVN-944 has broad anti-cancer activities, and can be used for multiple myeloma (MM) and acute myeloid leukemia (AML) research.
    AVN-944
  • HY-B0553
    Methazolamide
    		Inhibitor 99.41%
    Methazolamide (L584601) is a BBB-penetrable and orally active carbonic anhydrase inhibitor, with a Ki of 14 nM for human carbonic anhydrase II. Methazolamide can reduce intraocular pressure and has a neuroprotective effect, being able to inhibit neuronal apoptosis. Methazolamide can be used in the research of ophthalmic diseases such as glaucoma and cerebrovascular diseases such as subarachnoid hemorrhage.
    Methazolamide
  • HY-12294A
    PEAQX tetrasodium hydrate
    		Activator 98.0%
    PEAQX tetrasodium hydrate (NVP-AAM077 tetrasodium hydrate) is a tetrasodium hydrate of PEAQX (HY-12294). PEAQX tetrasodium hydrate is an orally active and selective NMDA antagonist, with IC50 values of 270 nM and 29.6 μM for hNMDAR 1A/2A and hNMDAR 1A/2B, respectively. PEAQX tetrasodium hydrate can promote the activation of caspase-3 and induce cell apoptosis in cortical striatal slice cultures.
    PEAQX tetrasodium hydrate
  • HY-101985
    BV02
    		99.75%
    BV02 is a 14-3-3 inhibitor and an antibacterial agent. BV02 enhances the cleavage of PARP and caspase-3. BV02 induces Apoptosis, Autophagy, and enhances Akt activation. BV02 has anti-B. melitensis infection and epilepsy-promoting effects. BV02 can also be used in colitis research.
    BV02
  • HY-128707
    Z-LEVD-FMK
    		Inhibitor 98.0%
    Z-LEVD-FMK is a cell-permeable caspase-4 inhibitor. Z-LEVD-FMK blocks ER stress-induced apoptosis in cancer cells.
    Z-LEVD-FMK
  • HY-Y1881B
    Copper sulfate pentahydrate, for cell culture, 98%
    		Activator 98.00%
    Copper sulfate pentahydrate, for cell culture, 98% is a biochemical reagent. Copper sulfate pentahydrate, for cell culture, 98% reduces the production of ROS and the expression levels of MyD88 as well as c-Rel genes. Copper sulfate pentahydrate, for cell culture, 98% decreases the activities of T-SOD, CAT, and GSH, increases the activities of caspase-3, caspase-8, and caspase-9. Copper sulfate pentahydrate, for cell culture, 98% is cytotoxic to various cells.
    Copper sulfate pentahydrate, for cell culture, 98%
  • HY-15586
    L67
    		Activator 98.0%
    L67 (DNA Ligase Inhibitor) is a competitive DNA ligase inhibitor that effectively inhibits DNA ligases I/III (both IC50 are 10 μM). L67 can cause nuclear DNA damage by reducing levels of mitochondrial DNA and increasing levels of mitochondrially-generated ROS. L67 also activates the Caspase 1-dependent apoptosis pathway in cancer cells, can be used in cancer research.
    L67
  • HY-116572A
    TASIN-1
    		Activator 98.09%
    TASIN-1 is a selective inhibitor of truncated APCTR (adenomatous polyposis coli gene) that exerts cytotoxic effects by inhibiting cholesterol biosynthesis. TASIN-1 specifically targets colorectal cancer (CRC) cells carrying APC truncated mutations, while having no significant toxicity to wild-type APC cells. TASIN-1 exerts cytotoxic effects by targeting Emopamil binding protein (EBP) to inhibit cholesterol biosynthesis, triggering endoplasmic reticulum (ER) stress, reactive oxygen species (ROS) generation, and JNK-mediated apoptosis, and inhibiting Akt survival signaling. TASIN-1 can be used to prevent and intervene in APC mutant colorectal cancer.
    TASIN-1
  • HY-B0942
    Benzethonium chloride
    		Activator 98.47%
    Benzethonium chloride inhibits nicotinic acetylcholine receptors in human recombinant α7 and α4β2 neurons in Xenopus laevis oocytes, which has antibacterial, anticancer, antisepsis and disinfection activity. Benzethonium chloride induced Apoptosis and activated caspases in cancer cell lines. Benzethonium chloride ablates the tumor-forming ability of FaDu cells, delays the growth of xenograft tumors in vivo.
    Benzethonium chloride
  • HY-B1971
    Deltamethrin
    		99.93%
    Deltamethrin (Decamethrin) is an orally active synthetic pyrethroid insecticide. Deltamethrin induces oxidative stress and results in inflammation and apoptosis via inhibiting Nrf2/HO-1 pathway. Deltamethrin has an anticancer effect by inducing apoptosis. Deltamethrin can be used extensively in pest control.
    Deltamethrin
Cat. No. Product Name / Synonyms Species Source
Cat. No. Product Name / Synonyms Application Reactivity
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Download Caspase Signaling Pathway Map.

Upon binding to their cognate ligand, death receptors such as Fas and TRAILR can activate initiator Caspases (Pro-caspase 8 and Pro-caspase 10) through dimerization mediated by adaptor proteins such as FADD and TRADD. Active Caspase 8 and Caspase 10 then cleave and activate the effector Caspase 3, 6 and 7, leading to apoptosis. ROS/DNA damage and ER stress trigger Caspase 2 activation. Active Caspase 2 cleaves and activates Caspase 3 and initiates apoptosis directly. Caspase 2, 8 and 10 can also cleave Bid, stimulate mitochondrial outer membrane permeabilization (MOMP) and initiate the intrinsic apoptotic pathway. Following MOMP, mitochondrial intermembrane space proteins such as Smac and Cytochrome C are released into the cytosol. Cytochrome C interacts with Apaf-1, triggering apoptosome assembly, which activates Caspase 9. Active Caspase 9, in turn, activates Caspase 3, 6 and 7, leading to apoptosis. Mitochondrial release of Smac facilitates apoptosis by blocking the inhibitor of apoptosis (IAP) proteins. 

 

Following the binding of TNF to TNFR1, TNFR1 binds to TRADD, which recruits RIPK1, TRAF2/5 and cIAP1/2 to form TNFR1 signaling complex I. Formation of the complex IIa and complex IIb is initiated either by RIPK1 deubiquitylation mediated by CYLD or by RIPK1 non-ubiquitylation due to depletion of cIAPs. The Pro-caspase 8 homodimer in complex IIa and complex IIb generates active Caspase 8. This active Caspase 8 in the cytosol then carries out cleavage reactions to activate downstream executioner caspases and thus induce classical apoptosis[1][2]. 

 

Reference:

[1]. Thomas C, et al. Caspases in retinal ganglion cell death and axon regeneration. Cell Death Discovery volume 3, Article number: 17032 (2017).
[2]. Brenner D, et al. Regulation of tumour necrosis factor signalling: live or let die. Nat Rev Immunol. 2015 Jun;15(6):362-74.

Caspase Isoform Comparison

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