1. Signaling Pathways
  2. Apoptosis
  3. Caspase

Caspase

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.

Cat. No. Product Name Effect Purity Chemical Structure
  • HY-137038
    N-a-Tosyl-L-lysinyl-chloromethylketone hydrochloride
    Inhibitor
    N-a-Tosyl-L-lysinyl-chloromethylketone hydrochloride (TLCK hydrochloride) is an irreversible inhibitor for serine protease, which inhibits trypsin and trypsin-like protease by alkylating histidine residues in their active site. N-a-Tosyl-L-lysinyl-chloromethylketone hydrochloride inhibits caspase-3, caspase-6 and caspase-7, with IC50s of 12.0, 54.5 and 19.3 μM, respectively. N-a-Tosyl-L-lysinyl-chloromethylketone hydrochloride induces apoptosis in cell HL-60, and inhibits the decrease in mitochondrial transmembrane potential during apoptosis.
    N-a-Tosyl-L-lysinyl-chloromethylketone hydrochloride
  • HY-158820A
    Cosdosiran sodium
    98.48%
    Cosdosiran sodium is a chemically modified siRNA designed to temporarily inhibit expression of the caspase 2 protein and can be used for the study of nonarteritic anterior ischemic optic neuropathy and other optic neuropathies such as glaucoma that result in the death of retinal ganglion cells.?
    Cosdosiran sodium
  • 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-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-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-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-penatrable 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-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
Cat. No. Product Name / Synonyms Species Source
Cat. No. Product Name / Synonyms Application Reactivity

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.

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