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-N2099
    Onjisaponin B
    		Inhibitor 99.10%
    Onjisaponin B is an orally active natural product derived from Polygala tenuifolia. Onjisaponin B inhibits NF-κB p65. Onjisaponin B enhances autophagy and accelerates the degradation of mutant α-synuclein and huntingtin. Onjisaponin B reduces β-amyloid (Aβ) production. Onjisaponin B reduces radiation-induced cell apoptosis. Onjisaponin B has anti-oxidant and anti-inflammatory activities. Onjisaponin B can be used for neurological disease and radiation injury study, and its metabolite tenuifolin (TF) can enter the brain through the BBB.
    Onjisaponin B
  • HY-131113
    N-Nitrosodibutylamine
    		99.96%
    N-Nitrosodibutylamine (N-Nitroso-di-n-butylamine) is a nitrosamine enriched in the drinking water. N-Nitrosodibutylamine regulates caspase pathway. N-Nitrosodibutylamine induces Apoptosis. N-Nitrosodibutylamine induces hepatocarcinoma and oxidative DNA damage.
    N-Nitrosodibutylamine
  • HY-141622
    SDZ 224-015
    		Inhibitor
    SDZ 224-015 is an orally active inhibitor of the interleukin-1 beta (IL-1β) converting enzyme and caspase-1. SDZ 224-015 possesses anti-COVID-19 activity, targeting Mpro (IC50 of 30 nM).
    SDZ 224-015
  • HY-115630
    cRIPGBM chloride
    		Activator 99.73%
    cRIPGBM chloride, an orally active, proapoptotic derivative. cRIPGBM can be generated from glioblastoma multiforme (GBM) cancer stem cells (CSCs). cRIPGBM(chloride) targets to receptor-interacting protein kinase 2 (RIPK2) to induce caspase 1-dependent apoptosis. cRIPGBM(chloride) suppresses the formation of RIPK2/TAK1 (prosurvival complex), and increases the formation of RIPK2/caspase 1 (proapoptotic complex). cRIPGBM(chloride) exerts potent anti-tumor activity in vivo in animal models.
    cRIPGBM chloride
  • HY-154795
    Magnesium isoglycyrrhizinate hydrate
    		Inhibitor 99.81%
    Magnesium isoglycyrrhizinate hydrate is the active component found in licorice plant (Glycyrrhiza glabra). Magnesium isoglycyrrhizinate hydrate exhibits anti-inflammatory activity through NLRP3 inflammasome pathway, and attenuates the chronic obstructive pulmonary disease in rats.
    Magnesium isoglycyrrhizinate hydrate
  • HY-120833
    Ac-Ile-Glu-Thr-Asp-pNA
    		99.90%
    Ac-Ile-Glu-Thr-Asp-pNA is a substrate for caspase-8. Caspase-8 binds to and cleaves the Ile-Glu-Thr-Asp (IETD) peptide sequence to release p-nitroalinide, which can be quantified by colorimetric detection at 405 nm as a measure of enzyme activity.
    Ac-Ile-Glu-Thr-Asp-pNA
  • HY-149800
    PARP-1-IN-3
    		Inducer 99.30%
    PARP-1-IN-3, a benzamide derivative, is a potent PARP-1 inhibitor with IC50 values of 0.25 nM and 2.34 nM for PARP-1 and PARP-2, respectively. PARP-1-IN-3 induces apoptosis and arrest cell cycle at G2/M phase. PARP-1-IN-3 can be used in research of cancer.
    PARP-1-IN-3
  • HY-N11774
    Euphornin
    		Modulator 98.09%
    Euphornin is a anticaner agent, that can be isolated from E. helioscopia. Euphornin induces apoptosis via caspase-mediated pathways. Euphornin induces cell cycle arrest by increasing the level of the phospho-CDK1 (Tyr15) protein.
    Euphornin
  • HY-N1931
    Epifriedelanol
    		Inducer ≥98.0%
    Epifriedelanol is a triterpenoid found in the root bark of Ulmus davidiana. Epifriedelanol induces apoptosis in DU145 cells. Epifriedelanol has antitumor and anti-inflammatory activities. Epifriedelanol inhibits cellular senescence in human primary cells.
    Epifriedelanol
  • HY-P2616A
    Mca-YVADAP-Lys(Dnp)-OH TFA
    		Chemical 99.45%
    Mca-YVADAP-Lys(Dnp)-OH TFA is a fluorogenic substrate for caspase-1 and angiotensin-converting enzyme 2 (ACE2).
    Mca-YVADAP-Lys(Dnp)-OH TFA
  • HY-B2046
    Simazine
    		99.72%
    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
  • HY-15733
    Lucidin
    		Activator 98.03%
    Lucidin (NSC 30546) is a natural component of madder and can induce mutations in bacterial and mammalian cells.
    Lucidin
  • HY-108164
    Aspidin BB
    		Activator 98.08%
    Aspidin BB is a phloroglucinol derivative, which can be isolated from the aerial part of Dryopteris championii. Aspidin BB has anticancer activity. Aspidin BB induces cell cycle arrest and apoptosis in human ovarian HO-8910 cells.
    Aspidin BB
  • HY-108312A
    AC-VEID-CHO TFA
    		Inhibitor 98.7%
    AC-VEID-CHO (TFA) is a peptide-derived caspase inhibitor and has potency of inhibition for Caspase-6, Caspase-3 and Caspase-7 with IC50 values of 16.2 nM, 13.6 nM and 162.1 nM, respectively. AC-VEID-CHO (TFA) can be used for the research of neurodegenerative conditions including Alzheimer’s and Huntington’s disease.
    AC-VEID-CHO TFA
  • 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-109076
    Tigilanol tiglate
    		Activator
    Tigilanol tiglate (EBC-46) is a protein kinase C (PKC)/C1 domain activator. Tigilanol tiglate is associated with mitochondrial/endoplasmic reticulum (ER) dysfunction, leading to activation of the unfolded protein response (UPRmt/ER) and subsequent induction of ATP depletion, organelles expansion, Caspase activation, gasdermin E cleavage, and terminal necrosis. Tigilanol tiglate, as a small anti-tumor molecule with immunomodulatory effects, can be used in the study of head and neck squamous cell carcinoma and soft tissue sarcoma.
    Tigilanol tiglate
  • HY-N6801
    Nivalenol
    		Activator 99.24%
    Nivalenol, classified as type B trichotecenes toxins produced by Fusarium graminearum, is a fungal metabolite present in agricultural product. Nivalenol induces cell death through caspase-dependent mechanisms and via the intrinsic apoptotic pathway. Nivalenol affects the immune system, causes emesis, growth retardation, reproductive disorders and has a haematotoxic/myelotoxic effect.
    Nivalenol
  • HY-120838
    Heptelidic acid
    		Inhibitor
    Heptelidic acid (Koningic acid) is a sesquiterpene antibiotic. Heptelidic acid inhibits Etoposide-induced apoptosis via downregulation of caspases. Koningic acid (KA) is a specific GAPDH inhibitor with an IC50of 90 μM.
    Heptelidic acid
  • HY-121713
    Aniline mustard
    		Activator 99.36%
    Aniline mustard (N, n-BIS (2-chloroethyl) aniline) is an anticancer agent.
    Aniline mustard
  • HY-12372
    Sanggenon G
    		Activator
    Sanggenon G is a cell-permeable and potent inhibitor of X-linked inhibitor of apoptosis protein (XIAP). Sanggenon G binds specifically to the BIR3 domain of XIAP with a binding affinity of 34.26 μM. Sanggenon G enhances caspase activation.
    Sanggenon G
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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