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-178351
    HDAC6-IN-67
    		Inhibitor
    HDAC6-IN-67 is a selective HDAC6 inhibitor (IC50 = 17.15 nM) that exhibits 19-fold selectivity over HDAC1. HDAC6-IN-67 selectively inhibits HDAC6 by interacting with Ser531 and His614. HDAC6-IN-67 induces apoptosis by inducing the cleavage of caspases 9, 8, 3, and PARP, upregulating Bax expression, and downregulating Bcl-2 expression. HDAC6-IN-67 effectively induces the acetylation of α-tubulin, without affecting histone H3 acetylation in MCF-7/ADR cells. HDAC6-IN-67 can be used for the study of breast cancer.
    HDAC6-IN-67
  • HY-170967
    IPH10
    IPH10 is an anti-cancer agent that exhibits a strong anti-tumor effect in vivo without hepatic and renal toxicity. IPH10 can significantly increase the content of ROS, decrease the mitochondrial membrane potential, and induce apoptosis in tumor cells.
    IPH10
  • HY-N7569
    Demethoxyfumitremorgin C
    		Activator
    Demethoxyfumitremorgin C is a secondary metabolite of the marine fungus, Aspergillus fumigatus. Demethoxyfumitremorgin C induces prostate cancer cell apoptosis. Demethoxyfumitremorgin C activates caspase-3, -8, and -9, leading to PARP/ cleavage.
    Demethoxyfumitremorgin C
  • HY-W011254
    Ac-VAD-CHO
    		Inhibitor
    Ac-VAD-CHO (Ac-Val-Ala-Asp-CHO) is a pan-caspase inhibitor. Ac-VAD-CHO inhibits dissipation of MMP and cytochrome c release in hypoxia-exposed cells.
    Ac-VAD-CHO
  • HY-RS01950
    Casp2 Mouse Pre-designed siRNA Set A
    		Inhibitor

    Casp2 Mouse Pre-designed siRNA Set A contains three designed siRNAs for Casp2 gene (Mouse), as well as a negative control, a positive control, and a FAM-labeled negative control.
    Casp2 Mouse Pre-designed siRNA Set A
  • HY-N11643
    Ganoderic acid Mk
    		Activator
    Ganoderic acid Mk (GA-Mk) is a triterpenoid acid, that can be isolated from the mycelia of Ganoderma lucidum. Ganoderic acid Mk is efficiently anti-proliferative and can induce apoptosis of HeLa cells by mitochondria-mediated pathway. Ganoderic acid Mk can be used for cervical cancer research.
    Ganoderic acid Mk
  • HY-N0361S
    Dihydrocapsaicin-d3
    		Inhibitor
    Dihydrocapsaicin-d3 is the deuterium labeled Dihydrocapsaicin (HY-N0361). Dihydrocapsaicin, a capsaicin, is a potent and selective TRPV1 (transient receptor potential vanilloid channel 1) agonist. Dihydrocapsaicin reduces AIF, Bax, and Caspase-3 expressions, and increased Bcl-2, Bcl-xL and p-Akt levels. Dihydrocapsaicin enhances the hypothermia-induced neuroprotection following ischemic stroke via PI3K/Akt regulation in rat.
    Dihydrocapsaicin-d<sub>3</sub>
  • HY-P3476
    Mca-VDQVDGW-Lys(Dnp)-NH2
    		Substrate
    Mca-VDQVDGW-Lys(Dnp)-NH2 is a fluorogenic substrate of caspase-7. Mca-VDQVDGW-K(Dnp)-NH2 can be used to quantify caspase-7 activity.
    Mca-VDQVDGW-Lys(Dnp)-NH2
  • HY-RS01955
    CASP4 Human Pre-designed siRNA Set A
    		Inhibitor

    CASP4 Human Pre-designed siRNA Set A contains three designed siRNAs for CASP4 gene (Human), as well as a negative control, a positive control, and a FAM-labeled negative control.
    CASP4 Human Pre-designed siRNA Set A
  • HY-P10452
    Ac-LEVDGWK(Dnp)-NH2
    Ac-LEVDGWK(Dnp)-NH2 is a substrate for Caspase-3, and can be used to detect Caspase-3 activity.
    Ac-LEVDGWK(Dnp)-NH2
  • HY-P4401A
    Z-VEID-AFC TFA
    Z-VEID-AFC TFA is the trifluoroacetate salt of Z-VEID-AFC (HY-P4401). Z-VEID-AFC TFA is a fluorescent substrate for caspase-6. When Z-VEID-AFC TFA is cleaved by caspase-6, 7-amino-4-trifluoromethylcoumarin (AFC) is released, and its fluorescence can be used to quantify caspase-6 activity (Ex/Em: 400/505 nm) .
    Z-VEID-AFC TFA
  • HY-P10832
    ATWLPPRAANLLMAAS
    		Activator
    ATWLPPRAANLLMAAS is a chimeric peptide with anti-angiogenic and potent anti-tumor effects. ATWLPPRAANLLMAAS can inhibit the proliferation, viability, migration, and invasion of human hepatocellular carcinoma cells, and induce apoptosis..
    ATWLPPRAANLLMAAS
  • HY-130476
    Satratoxin G
    		Activator
    Satratoxin G is a large cyclic mucor toxin. Satratoxin G induces apoptosis by activation of caspase .
    Satratoxin G
  • HY-P4392
    Z-VAD-AMC
    Z-VAD-AMC is a substrate of caspase-9.
    Z-VAD-AMC
  • HY-P10241
    Ac-LEHD-CHO
    		Inhibitor
    Ac-LEHD-CHO is an inhibitor for caspase 8/9. Ac-LEHD-CHO prevents GalN/TNF-α-induced hepatotoxicity and hepatocyte apoptosis.
    Ac-LEHD-CHO
  • HY-19696S2
    Tauroursodeoxycholate-d4-1
    		Inhibitor
    Tauroursodeoxycholate-d4-1 is the deuterium labeled Tauroursodeoxycholate. Tauroursodeoxycholate (Tauroursodeoxycholic acid) 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.
    Tauroursodeoxycholate-d<sub>4</sub>-1
  • HY-P1094
    AZ-10417808
    		Inhibitor
    AZ-10417808 is a selective caspase-3 inhibitor. AZ-10417808 blocks apoptosis signaling pathway by inhibiting caspase-3 activity. AZ-10417808 can be used to study the effect of nicotine on plasmacytoid dendritic cell migration.
    AZ-10417808
  • HY-178133
    Pim-1 kinase-IN-14
    		Activator
    Pim-1 kinase-IN-14 is a PIM-1 kinase inhibitor with an IC50 value of 94 nM. Pim-1 kinase-IN-14 shows broad-spectrum and high-efficiency anticancer activity against multiple human cancer cell lines, including liver cancer (HepG-2), colon cancer (Caco-2), myeloid leukemia (NFS-60), and prostate cancer (PC-3) cells. Pim-1 kinase-IN-14exerts its anticancer effects by inducing apoptosis and activating caspase 3/7. Pim-1 kinase-IN-14 can be used for the study of cancers associated with PIM-1 kinase overexpression.
    Pim-1 kinase-IN-14
  • HY-178380
    HDAC8-IN-14
    		Activator
    HDAC8-IN-14, a curcuminoid derivative, is a selective HDAC8 inhibitor with a Ki of 9 nM. HDAC8-IN-14 induces the production of reactive oxygen species (ROS), disrupts mitochondrial membrane potential, and promotes apoptosis. HDAC8-IN-14 can significantly promote the accumulation of cells in the sub-G0/G1 phase, consistent with apoptotic or necrotic cell death. HDAC8-IN-14 induces upregulation of cytochrome c, cleaved caspase-3, and the pro-apoptotic protein Bak while leaving the anti-apoptotic Bcl-2 levels unaltered. HDAC8-IN-14 can be used for the study of leukemia.
    HDAC8-IN-14
  • HY-P5938
    Ac-AAVALLPAVLLALLAP-YVAD-CHO
    		Inhibitor
    Ac-AAVALLPAVLLALLAP-YVAD-CHO is a cell-permeable caspase-1 inhibitor that has antitumor activity.
    Ac-AAVALLPAVLLALLAP-YVAD-CHO
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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