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-N0716A
    Berberine hemisulfate
    		Inhibitor 99.63%
    Berberine hemisulfate is the hemisulfate form of Berberine (HY-N0716). Berberine hemisulfate is an alkaloid isolated from the Chinese herbal medicine Huanglian. Berberine hemisulfate exhibits anti-inflammatory, antibiobic, antitumor, cardiovascular protective and neuroprotective activity.
    Berberine hemisulfate
  • HY-10805
    Almorexant
    		Activator 99.96%
    Almorexant (ACT 078573) is an orally active, potent and competitive dual orexin receptor antagonist, with Kd values of 1.3 nM (OX1) and 0.17 nM (OX2), respectively. Almorexant reversibly blocks signaling of orexin-A and orexin-B peptides. Almorexant totally blocked the intracellular Ca2+ signal pathway. Almorexant stimulates caspase-3 activity in AsPC-1 cells and induces apoptosis.
    Almorexant
  • HY-P99053
    Tralokinumab
    		Inhibitor 99.12%
    Tralokinumab (CAT354) is a humanized IgG4 monoclonal antibody that specifically binds to and neutralizes IL-13. Tralokinumab can be used in the research of diseases such as asthma, atopic dermatitis, and pulmonary fibrosis.
    Tralokinumab
  • HY-17583
    Griseofulvin
    		99.07%
    Griseofulvin is an orally active antifungal antibiotic with antitumor activity. Griseofulvin induces apoptosis and G2/M cell cycle arrest in cancer cells. Griseofulvin also has cardiovascular modulatory activity, reducing angina pectoris, relieving hand artery spasm associated with onychomycosis, and peripheral vascular diseases such as shoulder-hand syndrome.
    Griseofulvin
  • HY-N0281
    Daphnetin
    		Inducer 99.77%
    Daphnetin (7,8-dihydroxycoumarin), one coumarin derivative can be found in plants of the Genus Daphne, is a potent, oral active protein kinase inhibitor, with IC50s of 7.67 μM, 9.33 μM and 25.01 μM for EGFR, PKA and PKC in vitro, respectively. Daphnetin triggers ROS-induced cell apoptosis and induces cytoprotective autophagy by modulating the AMPK/Akt/mTOR pathway. Daphnetin has anti-inflammation activitity and inhibits TNF-α, IL-1β, ROS, and MDA production. Daphnetin has schizontocidal activity against malaria parasites. Daphnetin can be used for rheumatoid arthritis , cancer and anti-malarian research.
    Daphnetin
  • 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
  • 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-W269593
    Perfluorodecanoic acid
    		Inhibitor 98.0%
    Perfluorodecanoic acid (PFDA) is an orally active perfluoroalkyl substance. Perfluorodecanoic acid causes dysfunction of rat fetal Leydig cells via endoplasmic reticulum stress-mediated changes in lipid components. Perfluorodecanoic acid reduces testosterone biosynthesis in rat R2C Leydig cells by inducing endoplasmic reticulum stress. Perfluorodecanoic acid can be used in studies related to fetal Leydig cell dysfunction.
    Perfluorodecanoic acid
  • 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-129960
    L-Selenocystine
    		Inhibitor 98.0%
    L-Selenocystine is a selenium-containing amino acid. L-Selenocystine has redox properties. L-Selenocystine is cytotoxic to various tumor cells and can induce the production of ROS and apoptosis. L-Selenocystine can block the Nrf2 and autophagy pathways. L-Selenocystine has anti-tumor activity.
    L-Selenocystine
  • HY-145765
    JQAD1
    		Inducer 98.24%
    JQAD1 is a CRBN-dependent PROTAC that selectively targets EP300 for degradation. JQAD1 suppresses EP300 expression and the H3K27ac modification. JQAD1 induces apoptosis. JQAD1 can be used in research of cancer.
    JQAD1
  • HY-126741
    Azadirachtin
    		Activator 99.06%
    Azadirachtin is an oral active triterpenoid compound with anticancer, antimalarial, anti-inflammatory, and insecticidal activities. Azadirachtin induces cell apoptosis through the mitochondrial pathway (by inhibiting Bcl-2/Bax ratio or activating Apaf-1 and caspase-3) or through death receptors (by inhibiting TNFR activation). Additionally, Azadirachtin exerts its anti-inflammatory effects by inhibiting NF-кB signaling pathway activation, and it exhibits insecticidal activity by inducing apoptosis in insect cells.
    Azadirachtin
  • HY-N0591
    Dehydrocostus Lactone
    		99.98%
    Dehydrocostus Lactone ((-)-Dehydrocostus lactone) is a natural sesquiterpene that can be isolated from Saussurea lappa. Dehydrocostus Lactone has multiple activities such as anti-inflammatory, antibacterial, anti-tumor, and immunomodulatory effects. Dehydrocostus Lactone has an MIC of 2 µg/mL against Mycobacterium tuberculosis. Dehydrocostus Lactone can also inhibit the killing activity of cytotoxic T lymphocytes and induce apoptosis in tumor cells.
    Dehydrocostus Lactone
  • HY-112137
    Trehalose-6,6'-dibehenate
    		99.92%
    Trehalose-6,6'-dibehenate is an orally active glycolipid. Trehalose-6,6'-dibehenate activates Mincle and inflammasome, inducing IL-1β secretion in a caspase activity-dependent manner. Trehalose-6,6'-dibehenate exerts a Myd88-dependent adjuvant activity. Trehalose-6,6'-dibehenate induces Th-1/Th-17 immune responses.
    Trehalose-6,6'-dibehenate
  • 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-136241
    OT-82
    		Activator 99.95%
    OT-82 is a potent, selective and orally active inhibitor of NAMPT. OT-82 is selectively toxic to cells of hematopoietic origin and?induces cell death in a NAD+ dependent manner. OT-82 is a promising antineoplastic agent for the study of hematological malignancies.
    OT-82
  • 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-W020050
    Cystamine dihydrochloride
    		Inhibitor 99.92%
    Cystamine (dihydrochloride) is the disulfide form of the free thiol, cysteamine. Cystamine is an orally active transglutaminase (Tgase) inhibitor. Cystamine also has inhibition activity for caspase-3 with an IC50 value of 23.6 μM. Cystamine can be used for the research of severals diseases including Huntington's disease (HD) .
    Cystamine dihydrochloride
  • HY-160229
    ssRNA40 sodium
    		Activator 98.34%
    ssRNA40 sodium (R-1075 sodium) is a single-stranded RNA40 derived from HIV-1. ssRNA40 sodium activates the TLR7, TLR8, TLR2, RIG-I, MDA5, MyD88, Caspase-3, IRE1α, NLRP3 inflammasome and IRF7 signaling pathways. ssRNA40 sodium alters mRNA expression in neutrophils, induces pro-inflammatory cytokines, ROS, autophagy (autophagy), pyroptosis (pyroptosis), neuronal death, neurodegeneration, aggregate formation and NK cell activation. ssRNA40 sodium activates the expression of CD62L, CD11b, CD69, MX1, OAS1, ATG7, LC3B and XBP1 in immune cell and neuronal populations. ssRNA40 sodium causes cortical neuron loss and axonal damage in mice in a TLR7-dependent manner. ssRNA40 sodium can be used in research on HIV-1 infection, neurodegeneration, COVID-19 and HIV-associated neurological disorders.
    ssRNA40 sodium
  • HY-B1302
    Quinidine hydrochloride monohydrate
    		Activator 99.97%
    Quinidine hydrochloride monohydrate is an orally active antiarrhythmic agent. Quinidine hydrochloride monohydrate reduces the expression level of P-gp, inhibits P-gp-mediated efflux, increases the intracellular accumulation of P-gp substrates, induces PARP cleavage and Caspase-3 activation, and elevates the proportion of Apoptotic cells at the sub-G1 phase. Quinidine hydrochloride monohydrate exerts sustained block and open-channel block effects on IK(f). Quinidine hydrochloride monohydrate alters the urinary metabolic ratio of Amphetamine, modulates the Pentylenetetrazol-induced seizure threshold, and regulates the anticonvulsant effect of Dextromethorphan. Quinidine hydrochloride monohydrate can be used in studies related to uterine sarcoma and seizures.
    Quinidine hydrochloride monohydrate
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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