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-P2617
    Ac-WEHD-AFC
    Ac-WEHD-AFC is a fluorogenic caspase-1 substrate. Ac-WEHD-AFC can measure caspase-1 fluorogenic activity and can be used for the research of tumor and inflammation.
    Ac-WEHD-AFC
  • HY-168877
    FMP
    		Activator
    FMP is a Platinum(IV) complexe. FMP significantly upregulates the expression of γ-H2AX and p53. FMP increases the production of ROS. FMP markedly upregulates the expressions of Apoptosis-related proteins (DR5, Fas, caspase-8, Cyt-c, caspase-3, cleaved-PARP1, Bax). FMP shows antiproliferative activity against breast cancer.
    FMP
  • HY-RS01961
    CASP6 Rat Pre-designed siRNA Set A
    		Inhibitor

    CASP6 Rat Pre-designed siRNA Set A contains three designed siRNAs for CASP6 gene (Rat), as well as a negative control, a positive control, and a FAM-labeled negative control.
    CASP6 Rat Pre-designed siRNA Set A
    CASP6 Rat Pre-designed siRNA Set A
  • HY-N6940R
    Prosapogenin A (Standard)
    		Activator
    Prosapogenin A (Standard) is the analytical standard of Prosapogenin A. This product is intended for research and analytical applications. Prosapogenin A, a natural product from Veratrum, induces apoptosis in human cancer cells in vitro via inhibition of the STAT3 signaling pathway and glycolysis.
    Prosapogenin A (Standard)
  • HY-Y0152R
    Cinchonine (Standard)
    		Activator
    Cinchonine (Standard) is the analytical standard of Cinchonine. This product is intended for research and analytical applications. Cinchonine is a natural compound present in Cinchona bark with antimalarial, antitumor, anti-inflammatory, anti platelet-aggregation and anti-obesity properties. Cinchonine inhibits cells proliferation and autophagy and induces apoptosis through activation of Caspase-3. Cinchonine activates endoplasmic reticulum stress-induced apoptosis in human liver cancer cells.
    Cinchonine (Standard)
  • HY-117614
    WF-210
    		Activator
    WF-210 is a potent procaspase-3 activator with an EC50 value of 0.95 μM. WF-210 induces Apoptosis. WF-210 has anti-tumor activity.
    WF-210
  • HY-159891
    Microtubule destabilizing agent-2
    		Activator
    Microtubule destabilizing agent-2 (Compound 21) is an orally active and selective antitumor compound targeting microtubule protein. Microtubule destabilizing agent-2 destabilizes microtubule proteins and inhibits microtubule polymers. Microtubule destabilizing agent-2 arrests the G0/G1 phase in human tumor cells. Microtubule destabilizing agent-2 induces Apoptosis by activating the cascade pathway of caspases. Microtubule destabilizing agent-2 has anti-inflammatory activity, as inhibiting TNF-α and IL-6 in vitro. Microtubule destabilizing agent-2 reduces tumors growth in xenograft mice.
    Microtubule destabilizing agent-2
  • HY-13610B
    N1,N11-Diethylnorspermine hydrobromide
    		Activator
    N1,N11-Diethylnorspermine hydrobromide is a potent anticancer agent. N1,N11-Diethylnorspermine hydrobromide is a spermine analog that activates polyamine catabolism. N1,N11-Diethylnorspermine hydrobromide induces the release of cytochrome c from mitochondria, resulting in activation of caspase 3. N1,N11-Diethylnorspermine hydrobromide kills glioblastoma multiforme (GBM) cells through induction of SSAT (spermidine/spermine N1-acetyltransferase) coupled with H2O2 production.
    N1,N11-Diethylnorspermine hydrobromide
  • HY-172393
    TCF4/β-catenin-IN-1
    		Inducer
    TCF4/β-catenin-IN-1 (Compound 8b) is an inhibitor of TCF4/β-catenin, and induces apoptosis. TCF4/β-catenin-IN-1 up-regulates p53, caspase-3, caspase-8, caspase-9 levels and Bax protein expression as well as down-regulates Bcl-2 protein expression. TCF4/β-catenin-IN-1 can inhibit CYP3A4, CYP1A2, CYP2C19, and shows promising cytotoxic activity in cancer cells.
    TCF4/β-catenin-IN-1
  • HY-N0551R
    Wedelolactone (Standard)
    		Inhibitor
    Wedelolactone (Standard) is the analytical standard of Wedelolactone. This product is intended for research and analytical applications. Wedelolactone suppresses LPS-induced caspase-11 expression by directly inhibits the IKK Complex. Wedelolactone also inhibits 5-lipoxygenase (5-Lox) with an IC50 of 2.5 μM. Wedelolactone induces caspase-dependent apoptosis in prostate cancer cells via downregulation of PKCε without inhibiting Akt. Wedelolactone can extract from Eclipta alba, and it can be used for the research of cancer.
    Wedelolactone (Standard)
  • HY-P10103
    Smac-N7 peptide
    Smac-N7 peptide, the seven N-terminal amino acid of the mitochondrial protein Smac (second mitochondria-derived activator of caspase), cannot pass through the cell membrane.
    Smac-N7 peptide
  • HY-P2012
    TRP-601
    		Inhibitor
    TRP-601 is a caspase inhibitor. TRP-601 reversed the increased expression of active caspase-2, the activation of endogenous apoptotic pathway and the up-regulation of key protein triggered by hyperoxia.
    TRP-601
  • HY-N2802
    Euptox A
    		Inducer
    Euptox A (9-Oxo-10, 11-dehydroageraphorone), a cadenine sesquiterpene, is the main toxin that can be isolated from Eupatorium adenophorum. Euptox A induces apoptosis by improving the gene expression level of apoptotic proteases such as caspase-10 in HeLa cells.
    Euptox A
  • HY-116204
    SKLB70326
    		Activator
    SKLB70326 is a small molecule inhibitor of cell cycle progression that induces cell cycle arrest and apoptosis in human hepatocellular carcinoma cells. SKLB70326 is involved in downregulating cyclin-dependent kinase (CDK) 2, CDK4, and CDK6, while also activating PARP, caspase-3, caspase-9, and Bax, and downregulating Bcl-2.
    SKLB70326
  • HY-152756
    Caspase-3/7 activator 2
    		Activator
    Caspase-3/7 activator 2 is an effective activator of Caspase-3/7. Caspase-3/7 activator 2 has tumor selectivity, anti-proliferative activity and high Apoptosis-inducing ability.
    Caspase-3/7 activator 2
  • HY-N12235
    Sarglaroids F
    		Inhibitor
    Sarglaroids F (compound 6) is an anti-inflammatory agent isolated from the roots of Grass Coral. Sarglaroids F inhibits LPS/ATP-induced IL-1β release by affecting K+ efflux and reducing Caspase-1(P20) levels. Sarglaroids F is not cytotoxic to RAW264.7 cells.
    Sarglaroids F
  • HY-143235
    BRD4 Inhibitor-15
    		Activator
    BRD4 Inhibitor-15 (compound 13) is a potent BRD4 inhibitor, with an IC50 of 18 nM. BRD4 Inhibitor-15 induces apoptosis of 22RV1 cells by regulating Bcl-2/Bax proteins and activating caspase-3 signaling pathway. BRD4 Inhibitor-15 down-regulates the c-Myc level in 22RV1 cells. BRD4 Inhibitor-15 can be used for prostate cancer research.
    BRD4 Inhibitor-15
  • HY-W041489R
    Chelidonic acid (Standard)
    		Inhibitor
    Chelidonic acid (Standard) is the analytical standard of Chelidonic acid. This product is intended for research and analytical applications. Chelidonic acid is a component of Chelidonium majus L., used as an antimicrobial. Chelidonic acid also shows anti-inflammatory activity. Chelidonic acid has potential to inhibit IL-6 production by blocking NF-κB and caspase-1. Chelidonic acid is a glutamate decarboxylase inhibitor, with a Ki of 1.2 μM.
    Chelidonic acid (Standard)
  • HY-N0716R
    Berberine (Standard)
    		Inhibitor
    Berberine (Standard) is the analytical standard of Berberine. This product is intended for research and analytical applications. Berberine (Natural Yellow 18) is an alkaloid isolated from the Chinese herbal medicine Huanglian, as an antibiotic. Berberine (Natural Yellow 18) induces reactive oxygen species (ROS) generation and inhibits DNA topoisomerase. Berberine (Natural Yellow 18) has antineoplastic properties. The sulfate form (HY-N0716B) improves bioavailability.
    Berberine (Standard)
  • HY-149517
    EGFR/BRAFV600E-IN-2
    		Activator
    EGFR/BRAFV600E-IN-2 (compound 3g) is a potential multi-target inhibitor of EGFR, BRAFV600E, and EGFRT790M, and an inducer of apoptosis. EGFR/BRAFV600E-IN-2 can activate caspase-3, 8, and Bax, and downregulate the anti-apoptotic protein Bcl2, inducing apoptosis. EGFR/BRAF V600E-IN-2 also has antioxidant activity and DPPH free radical scavenging potency.
    EGFR/BRAFV600E-IN-2
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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