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-RS01969
    CASP9 Human Pre-designed siRNA Set A
    		Inhibitor

    CASP9 Human Pre-designed siRNA Set A contains three designed siRNAs for CASP9 gene (Human), as well as a negative control, a positive control, and a FAM-labeled negative control.
    CASP9 Human Pre-designed siRNA Set A
    CASP9 Human Pre-designed siRNA Set A
  • HY-P5834
    Boc-AEVD-CHO
    		Inhibitor
    Boc-AEVD-CHO is a Caspase 8 inhibitor useful in the study of apoptosis and immune and inflammatory diseases.
    Boc-AEVD-CHO
  • HY-P5974
    Z-YVAD-pNA
    Z-YVAD-pNA (Z-Tyr-Val-Ala-Asp-pNA) is a caspase-1 substrate.
    Z-YVAD-pNA
  • HY-13559A
    Atiprimod dimaleate
    		Activator
    Atiprimod (Azaspirane) (dimaleate) is an anti-proliferative and anti-angiogenic agent that inhibits proliferation of cancer cell lines. Atiprimod (dimaleate) also induces Apoptosis and activates both caspase-9 and caspase-3 in T84 colon carcinoma cells. Atiprimod (dimaleate) inhibits both bFGF and VEGF induced proliferation and migration of human umbilical vein endothelial cells, resulting in disruption of cord formation. Atiprimod (dimaleate) reduces production of IL-6, VEGF and inhibits activation of Stat3.
    Atiprimod dimaleate
  • HY-N11648
    Ganoderic acid T1
    		Activator
    Ganoderic acid T1 is a deacetylated derivative of Ganoderic acid T. Ganoderic acid T1 attenuates antioxidant defense system and induces apoptosis of cancer cells. Ganoderic acid T1 decreases mitochondrial membrane potential and activates caspase-9 and caspase-3, to trigger apoptosis. Ganoderic acid T1 also increases the generation of intracellular ROS to produce pro-oxidant activities and cytotoxicity.
    Ganoderic acid T1
  • HY-117249
    Sanazole
    		Agonist
    Sanazole (AK-2123) is a hypoxic cell radiosensitizer. Sanazole enhances radiation-induced DNA strand breaks. In mouse fibroblast tumors, Sanazole increases nuclear condensation and fragmentation, as well as elevates caspase-3 activity, thereby enhancing radiation-induced apoptosis. These characteristics make Sanazole a promising candidate for research in tumor therapy.
    Sanazole
  • HY-P10084
    Ac-VAD-pNA
    Ac-VAD-pNA is a caspase-1 substrate. Ac-VAD-pNA can be used to detect caspase-1 activity.
    Ac-VAD-pNA
  • HY-W040329S
    2'-Deoxyadenosine-13C10,15N5
    		Activator
    2'-Deoxyadenosine-13C10,15N5 is 13C and 15N-labeled 2'-Deoxyadenosine (HY-W040329). 2′-Deoxyadenosine is an adenine nucleoside that inhibits glucose-stimulated insulin release. 2′-Deoxyadenosine inhibits glucose-stimulated increases seen in islet cyclic AMP (cAMP) accumulation. 2'-Deoxyadenosine activates caspase-3 and promotes apoptosis. 2'-Deoxyadenosine inhibits the activity of S-adenosyl-L-homocysteine hydrolase (SAHH). 2'-Deoxyadenosine inhibits the growth of various cells. 2'-Deoxyadenosine has an anticancer effect on colon cancer.
    2'-Deoxyadenosine-<sup>13</sup>C<sub>10</sub>,<sup>15</sup>N<sub>5</sub>
  • HY-155570
    Anticancer agent 137
    		Inducer
    Anticancer agent 137 (8q) is a potent PI3k inhibitor. Anticancer agent 137 has broad-spectrum anticancer activity. Anticancer agent 137 induces G2/M cell cycle arrest and apoptosis. Anticancer agent 137 increases cleaved PARP, caspase 3, and 7. Anticancer agent 137 can be used in research of cancer.
    Anticancer agent 137
  • HY-P2614
    Mca-DEVDAP-K(Dnp)-OH
    		Chemical
    Mca-DEVDAP-K(Dnp)-OH is a fluorogenic substrate for caspase-3.
    Mca-DEVDAP-K(Dnp)-OH
  • HY-N2071R
    Cedrol (Standard)
    		Activator
    Cedrol (Standard) is the analytical standard of Cedrol. This product is intended for research and analytical applications. Cedrol is a potent competitive inhibitor of cytochrome P-450(CYP) enzyme. Cedrol plays an anticancer role by inducing cell cycle arrest and Caspase-dependent apoptosis. Cedrol acts as a neutrophil agonist that can desensitize cells to subsequent stimulation of N-formyl peptides. Cedrol prevents neuropathic pain caused by chronic contractile injury by inhibiting oxidative stress and inflammation. In addition, Cedrol has antibacterial, hair loss prevention and anti-anxiety properties.
    Cedrol (Standard)
  • HY-168338
    CB2 receptor agonist 8
    		Activator
    CB2 receptor agonist 8 (Compound 17) is an agonist for cannabinoid receptor 2 (CB2 receptor). CB2 receptor agonist 8 exhibits cytotoxicity in cells U87, RPMI 8226, HL-60, and L929 with IC50s of 91.03, 16.29, 23.51 and 564.6 μM, respectively. CB2 receptor agonist 8 activates caspase 3/7, increases the expressions of pro-apoptotic genes BAX, BAD, BIM and tumor suppressor genes p53, and induces apoptosis in U87. CB2 receptor agonist 8 inhibits the migration of U87.
    CB2 receptor agonist 8
  • HY-N10018
    Cimiside E
    		Inhibitor
    Cimiside E (25-Anhydrocimigenol xyloside) is a triterpene xyloside, Cimiside E possesses apoptotic action on gastric cancer cells, with an IC50 value of 14.58 μM. Cimiside E induces cell cycle arrest at G2/M phase, and mediates apoptosis through the induction of the caspase cascade for both the extrinsic and intrinsic pathways.
    Cimiside E
  • HY-P5830
    Biotin-DEVD-CHO
    Biotin-DEVD-CHO can be used for affinity labeling of Caspase-8 following in vitro caspase cleavage.
    Biotin-DEVD-CHO
  • HY-RS01964
    Casp7 Rat Pre-designed siRNA Set A
    		Inhibitor

    Casp7 Rat Pre-designed siRNA Set A contains three designed siRNAs for Casp7 gene (Rat), as well as a negative control, a positive control, and a FAM-labeled negative control.
    Casp7 Rat Pre-designed siRNA Set A
    Casp7 Rat Pre-designed siRNA Set A
  • HY-169412
    MAPK-IN-3
    		Activator
    MAPK-IN-3 (Compound 4a) is an anti-proliferative agent that shows particularly strong inhibitory effects on KYSE 30, HCT 116, and HGC 27, with IC50 values of 0.57 μM, 3.27 μM, and 2.28 μM, respectively. MAPK-IN-3 blocks the cell cycle via a p53-dependent mechanism and induces cell apoptosis through a p53-independent mechanism. MAPK-IN-3 downregulates the expression of cell cycle-related proteins like Cyclin D1 and cyclin B1, upregulates pro-apoptotic proteins such as cleaved PARP, cleaved caspase-7, and cleaved caspase-9, and reduces the expression of anti-apoptotic proteins like Bcl-2. Additionally, MAPK-IN-3 increases the intracellular level of ROS in KYSE 30 cells and upregulates the expression of members of the MAPK signaling pathway associated with ROS, such as p-ERK, p-p38 and p-JNK.
    MAPK-IN-3
  • HY-P4222
    IETD-CHO
    		Inhibitor
    IETD-CHO (Caspase-8-IN-1) is a potent caspase-8 inhibitor.
    IETD-CHO
  • HY-RS01967
    Casp8 Rat Pre-designed siRNA Set A
    		Inhibitor

    Casp8 Rat Pre-designed siRNA Set A contains three designed siRNAs for Casp8 gene (Rat), as well as a negative control, a positive control, and a FAM-labeled negative control.
    Casp8 Rat Pre-designed siRNA Set A
    Casp8 Rat Pre-designed siRNA Set A
  • HY-155390
    Caspase-3 activator 3
    		Activator
    Caspase-3 activator 3 (compound 2h) induces apoptosis in HL-60 and K562 cells via significant caspase 3 activation. Caspase-3 activator 3 shows antileukemic acticity against HL-60 and K562 cells, with IC50 values of 42.89 and 33.61 μM, respectively.
    Caspase-3 activator 3
  • HY-101997
    BEPP hydrochloride
    		Activator
    BEPP hydrochloride is a double-stranded RNA-dependent protein kinase (PKR) inducer and antiviral agent. BEPP hydrochloride effectively inhibits the growth of human lung cancer cell lines overexpressing PKR and induces apoptosis and activates caspase-3 in sensitive cells. In addition, BEPP hydrochloride can also significantly inhibit vaccinia virus replication.
    BEPP hydrochloride
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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