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-N0716
    Berberine
    		Inhibitor
    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
  • HY-N2013R
    Aristolactam I (Standard)
    		Inhibitor
    Aristolactam I (Standard) is the analytical standard of Aristolactam I. This product is intended for research and analytical applications. Aristolactam I is an AQP1 inhibitor and Aristolochic acid I metabolite. Aristolactam I can be isolated from Aristolochia plants. Aristolactam I downregulates Twist1 expression, increases E-cadherin expression, and activates the TGF-β/Smad signaling pathway. Aristolactam I has anticancer activity against breast cancer. Aristolactam I is nephrotoxic. Aristolactam I is mainly used in the study of breast cancer and kidney diseases such as renal interstitial fibrosis.
    Aristolactam I (Standard)
  • HY-W415273
    Caspase-3-IN-2
    		Inhibitor
    Caspase-3-IN-2 (Compound 4d) is the inhibitor for α-Chymotrypsin. Caspase-3-IN-2 also exhibits inhibitory activity against HIV protease and caspase 3 with an inhibition rate of 57% and 51% at 100 μM.
    Caspase-3-IN-2
  • HY-B2046R
    Simazine (Standard)
    Simazine (Standard) is the analytical standard of Simazine (HY-B2046). This product is intended for research and analytical applications. Simazine is a triazine herbicide. Simazine is widely used in agriculture, potted plant and tree production. In addition, Simazine can induce the apoptosis of immune cells in the spleen of mice and inhibit the proliferation of B cells and T cells in mice.
    Simazine (Standard)
  • HY-N0758R
    Barlerin (Standard)
    Barlerin (Standard) is the analytical standard of Barlerin. This product is intended for research and analytical applications. Barlerin (8-O-Acetyl shanzhiside methyl ester) is an iridoid glucoside isolated from the leaves of Lamiophlomis rotata Kudo, a Chinese folk medicinal plant in Xi-zang. Barlerin (8-O-Acetyl shanzhiside methyl ester) could inhibt NF-κB.
    Barlerin (Standard)
  • HY-111523
    Isomahanine
    		Activator
    Isomahanine, carbazole alkaloid, is an antioxidative agent. Isomahanine has DPPH radical scavenging activity with an IC50 value of 24 μM.
    Isomahanine
  • HY-N0534R
    Vitexin-2"-O-rhamnoside (Standard)
    		Inhibitor
    Vitexin-2"-O-rhamnoside (Standard) is the analytical standard of Vitexin-2"-O-rhamnoside (HY-N0534). This product is intended for research and analytical applications. Vitexin-2"-O-rhamnoside is an orally active flavonoid glycoside. Vitexin-2"-O-rhamnoside inhibits Apoptosis, increases the phosphorylation levels of PI3K/Akt, inhibits caspase-3, SOD activity, and promotes cytokine (IL-2, IL-6, and IL-12) secretion. Vitexin-2"-O-rhamnoside strongly inhibits DNA synthesis in MCF-7 cells with an IC50 of 17.5 μM. Vitexin-2"-O-rhamnoside enhances immune function and improves the absorption of active compounds. Vitexin-2"-O-rhamnoside has antioxidant activity. Vitexin-2"-O-rhamnoside is used in the study of cardiovascular disease and immune-related diseases.
    Vitexin-2
  • HY-B0553R
    Methazolamide (Standard)
    		Inhibitor
    Methazolamide (Standard) is the analytical standard of Methazolamide. This product is intended for research and analytical applications. 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 (Standard)
  • HY-10396R
    Emricasan (Standard)
    		Inhibitor
    Emricasan (Standard) is the analytical standard of Emricasan. This product is intended for research and analytical applications. Emricasan (PF 03491390) is an orally active and irreversible pan-caspase inhibitor. Emricasan inhibits Zika virus (ZIKV)-induced increases in caspase-3 activity and protected human cortical neural progenitors.
    Emricasan (Standard)
  • HY-124083
    MPT0B214
    		Modulator
    MPT0B214 is a microtubule inhibitor that strongly binds to the colchicine binding site of tubulin, preventing tubulin polymerization. MPT0B214 induces apoptosis through a mitochondrial/caspase 9 dependent pathway and shows cytotoxicity across various human tumor cell lines. MPT0B214 can be used for cancer research.
    MPT0B214
  • HY-B1839R
    Fluazinam (Standard)
    		Activator
    Fluazinam (Standard) is the analytical standard of Fluazinam (HY-B1839). This product is intended for research and analytical applications. Fluazinam is a broad spectrum pyridinamine fungal inhibitor. Fluazinam is an orally active dinitroaniline fungicide. Fluazinam induces phosphorylation of JNK, activates p38 pathway, decreases Bcl-2, activates caspase-3, decreases complex I activity, increases Autophagy and Apoptosis. Fluazinam has strong antifungal activity against F. fujikuroi and B. maydis. Fluazinam has a negative impact on Brachydanio rerio and worker bees.
    Fluazinam (Standard)
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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