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-P4449A
    Ac-VRPR-AMC TFA
    		99.60%
    Ac-VRPR-AMC TFA is a fluorogenic metacaspase substrate. Ac-VRPR-AMC TFA can be used to assay metacaspase activity.
    Ac-VRPR-AMC TFA
  • HY-W106456
    3-Methoxy-9H-Carbazole
    		Activator 99.64%
    3-Methoxy-9H-Carbazole induces caspase-3 activities and the cellular generation of eactive oxygen species. 3-Methoxy-9H-Carbazole inhibits cancer cell proliferation and induces apoptosis.
    3-Methoxy-9H-Carbazole
  • HY-N2993
    Polyporenic acid C
    		Activator ≥99.0%
    Polyporenic acid C is a lanostane-type triterpenoid. Polyporenic acid C can be isolated from Poria cocos. Polyporenic acid C causes the cleavage of caspase-8 and caspase-3, as well as the cleavage of PARP. Polyporenic acid C reduces the phosphorylation level of Akt (Ser473), increases the phosphorylation of PTEN and p53 (Ser15), and activates JNK. Polyporenic acid C induces Apoptosis. Polyporenic acid C shows anticancer activity against non-small cell lung cancer.
    Polyporenic acid C
  • HY-124113
    4'-Bromo-resveratrol
    		99.94%
    4'-Bromo-resveratrol (4′‐BR) is a dual SIRT1/SIRT3 inhibitor with an IC50 of 0.2 mM for both targets. 4'-Bromo-resveratrol induces caspase-dependent apoptosis, induces G0/G1 cell cycle arrest, and inhiibits proliferation. 4'-Bromo-resveratrol reduces lactate production, glucose uptake, and NAD+/NADH ratio, and downregulates lactate dehydrogenase A and glucose transporter 1 (GLUT1). 4'-Bromo-resveratrol can be used for the research of melanoma.
    4'-Bromo-resveratrol
  • HY-19696AS
    Tauroursodeoxycholate-d4 sodium
    		Inhibitor 99.50%
    Tauroursodeoxycholate-d4 (sodium) is the deuterium labeled Tauroursodeoxycholate sodium. Tauroursodeoxycholate (Tauroursodeoxycholic acid; TUDCA) sodium is an endoplasmic reticulum (ER) stress inhibitor. Tauroursodeoxycholate significantly reduces expression of apoptosis molecules, such as caspase-3 and caspase-12. Tauroursodeoxycholate also inhibits ERK.
    Tauroursodeoxycholate-d<sub>4</sub> sodium
  • HY-N3138
    Ombuoside
    		Inhibitor 99.68%
    Ombuoside has antioxidant properties, inhibiting ROS production and apoptosis. Ombuoside exerts neuroprotective effects through the ERK-JNK-caspase-3 system. Ombuoside promotes Dopamine biosynthesis through TH and CREB activation. Ombuoside exhibits antimicrobial activity against several Gram-positive and Gram-negative bacteria, as well as Candida albicans
    Ombuoside
  • HY-124833
    Quinalizarin
    		Modulator
    Quinalizarin is a protein kinase CK2 inhibitor with a Ki of 0.052 μM. Quinalizarin exhibits antifungal and anticancer activities. Quinalizarin induces ROS production, apoptotic signaling, mitochondrial pathway activation, cell cycle arrest, and cytotoxicity in cancer cells. Quinalizarin inhibits hyphal growth, biofilm formation, and mature biofilm integrity of Candida albicans. Quinalizarin can be used in research related to cancer and fungal infections.
    Quinalizarin
  • HY-N4102
    5,7-Dihydroxy-4-methylcoumarin
    		Inhibitor 98.85%
    5,7-Dihydroxy-4-methylcoumarin is an antioxidant. 5,7-Dihydroxy-4-methylcoumarin protects mouse cochlear hair cells from Cisplatin-induced damage, enhances cell viability and inhibits apoptosis. 5,7-Dihydroxy-4-methylcoumarin downregulates phosphorylated JNK levels, increases the ratio of phosphorylated FoxO1 to total FoxO1, scavenges free radicals, reduces ROS accumulation, maintains mitochondrial membrane potential and alleviates mitochondrial dysfunction. 5,7-Dihydroxy-4-methylcoumarin downregulates the expression of caspase-3 and improves cell viability. 5,7-Dihydroxy-4-methylcoumarin can be used in studies related to ototoxicity.
    5,7-Dihydroxy-4-methylcoumarin
  • HY-N0674B
    Dehydrocorydaline (hydroxyl)
    		Activator 99.52%
    Dehydrocorydaline (13-Methylpalmatine) hydroxyl is an alkaloid that regulates protein expression of Bax, Bcl-2; activates caspase-7, caspase-8, and inactivates PARP. Dehydrocorydaline hydroxyl elevates p38 MAPK activation. Anti-inflammatory and anti-cancer activities. Dehydrocorydaline hydroxyl shows strong anti-malarial effects (IC50=38 nM), and low cytotoxicity (cell viability > 90%) using P. falciparum 3D7 strain.
    Dehydrocorydaline (hydroxyl)
  • HY-19696R
    Tauroursodeoxycholate (Standard)
    		Inhibitor
    Tauroursodeoxycholate (Standard) is the analytical standard of Tauroursodeoxycholate. This product is intended for research and analytical applications. Tauroursodeoxycholate (Tauroursodeoxycholic acid) is an endoplasmic reticulum (ER) stress inhibitor. Tauroursodeoxycholate significantly reduces expression of apoptosis molecules, such as caspase-3 and caspase-12. Tauroursodeoxycholate also inhibits ERK.
    Tauroursodeoxycholate (Standard)
  • HY-P0034
    Ac-DEVD-CMK
    		Inhibitor 98.81%
    Ac-DEVD-CMK (Caspase-3 Inhibitor III) is a selective and irreversible caspase-3 inhibitor. Ac-DEVD-CMK significantly inhibits apoptosis induced by high levels of glucose or Ingenol 3,20-dibenzoate?(HY-137295). Ac-DEVD-CMK can be used in a variety of experimental approaches to inhibit apoptosis.
    Ac-DEVD-CMK
  • HY-12412
    ML132
    		Inhibitor 98.75%
    ML132 (NCGC-00183434) is a selective caspase 1 inhibitor with an IC50 value of 0.023 nM. ML132 has good stability and can be used as a caspase 1 molecular probe. ML132 is applicable to research in the fields of anticancer and anti-inflammatory studies.
    ML132
  • HY-176860
    NEK7 degrader-1
    		Inhibitor 99.94%
    NEK7 degrader-1 is a NEK7 molecular glue degrader with a DC50 of 9  nM. NEK7 degrader-1 dose-dependently inhibits caspase-1 activity and IL-Ιβ release in macrophages in response to NLRP3 inflammasome activation. NEK7 degrader-1 can be used for autoinflammatory and autoimmune disorders like multiple sclerosis, neurodegeneraive diseases like Alzheimer's disease and cardiovascular and melabolic disorders like pericarditis and Type 2 diabetes research.
    NEK7 degrader-1
  • HY-10131
    Procaspase-3/6 activator 1
    		Activator 99.45%
    Procaspase-3/6 activator 1 (compound 1541) is a highly specific and robust activator of executioner procaspases-3 and -6, with EC50 values of 2.4 ± 0.2 and 2.8 ± 0.3 μM, respectively. Procaspase-3/6 activator 1 does not activate procaspases-1 or -7.
    Procaspase-3/6 activator 1
  • HY-N2736
    3′,4′,7-Trihydroxyflavone
    		Inhibitor 99.04%
    3′,4′,7-Trihydroxyflavone is an orally active inhibitor of OXA-48 (IC50 = 1.89 μM) and COX-1 (IC50 = 36.37 μM). 3′,4′,7-Trihydroxyflavone exhibits antioxidant and anti-inflammatory properties, inhibiting the release of inflammatory cytokines such as IL-6, IL-8, and TNF-α. 3′,4′,7-Trihydroxyflavone inhibits H2O2-induced neuronal apoptosis and ROS accumulation, and exerts anti-neuroinflammatory effects by suppressing the JNK-STAT1 pathway. 3′,4′,7-Trihydroxyflavone exhibits antimicrobial and antibiotic-modifying activities against multidrug-resistant Gram-negative enteric bacteria. 3′,4′,7-Trihydroxyflavone inhibits RANKL-induced osteoclast formation via NFATc1. 3′,4′,7-Trihydroxyflavone activates the CREB-BDNF axis and restores scopolamine (HY-N0296)-induced memory deficits in mice.
    3′,4′,7-Trihydroxyflavone
  • HY-153161
    CASP8-IN-1
    		Inhibitor 98.97%
    CASP8-IN-1 (Compound 63-R) is a selective inhibitor for caspase 8 (CASP8), with an IC50 of 0.7 μM. CASP8-IN-1 inhibits FasL-induced apoptosis in cell Jurkat.
    CASP8-IN-1
  • HY-101997
    BEPP hydrochloride
    		Activator 99.62%
    BEPP hydrochloride is a double-stranded RNA-dependent protein kinase (PKR) modulator. BEPP hydrochloride enhances the phosphorylation levels of PKR and eIF2α, activates caspase-3, upregulates the pro-apoptotic protein BAX, and downregulates the anti-apoptotic protein Bcl-2. BEPP hydrochloride inhibits vaccinia virus replication and exhibits selective cytotoxicity in cells expressing PKR. BEPP hydrochloride can be used in research related to cancer and viral infections.
    BEPP hydrochloride
  • HY-N6017
    Bakkenolide A
    		Activator 99.99%
    Bakkenolide A is an anticancer agent. Bakkenolide A reduces the viability of leukemia cells, inhibits cell colony formation and invasion, and downregulates the expression of HDAC3 in cells. Bakkenolide A downregulates the expression of pro-inflammatory cytokines including TNF-α, interleukins such as IL-1β, TGF-β1 and IFN-γ, as well as the expression of PI3K, PDK and PKC in leukemia cells. Bakkenolide A downregulates activated Akt, GSK and Bad, while upregulates Cyto-c, cleaved Caspase3 and cleaved Caspase7, induces apoptosis (apoptosis) in leukemia cells and thereby inhibits inflammatory responses in leukemia cells. Bakkenolide A significantly slows the growth of subcutaneous leukemia tumors in nude mice. Bakkenolide A is applicable to leukemia-related research.
    Bakkenolide A
  • HY-103349
    PETCM
    		Activator 99.68%
    PETCM is an activator of caspase-3 and acts as an cytochrome c (cyto c)-dependent manner. PETCM promotes Apaf-1 oligomerization and induces cell apoptosis in HeLa cells.
    PETCM
  • HY-N2135
    Puerarin 6''-O-Xyloside
    		99.81%
    Puerarin 6''-O-Xyloside is one of the major iso-flavones found in P. lobata. Puerarin 6''-O-Xyloside inhibits cancer cells proliferation, induces apoptosis by upregulating cleaved caspase-3, 7, 9, Bax and downregulating Bcl-2 levles and inhibits tumor growth in mice. Puerarin 6''-O-Xyloside has anti-osteoporotic activity in ovariectomized mice. Puerarin 6''-O-Xyloside inhibits mushroom tyrosinase with an IC50 of 513.8 μM. Puerarin 6''-O-Xyloside can be used for the research of human lung carcinoma, osteoporosis, melanosis and melanomar.
    Puerarin 6''-O-Xyloside
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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