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-16658B
    Z-VAD-FMK
    		Inhibitor 99.78%
    Z-VAD-FMK (Z-VAD(OH)-FMK) is a well-know pan caspase inhibitor, which does not inhibit ubiquitin carboxy-terminal hydrolase L1 (UCHL1) activity even at concentrations as high as 440 μM.
    Z-VAD-FMK
  • HY-12305
    Q-VD-OPh
    		Inhibitor 99.92%
    Q-VD-OPh is an irreversible pan-caspase inhibitor with potent antiapoptotic properties; inhibits caspase 7 with an IC50 of 48 nM and 25-400 nM for other caspases including caspase 1, 3, 8, 9, 10, and 12. Q-VD-OPh can inhibits HIV infection. Q-VD-OPh is able to cross the blood-brain barrier.
    Q-VD-OPh
  • HY-13755
    Sulforaphane
    		Inhibitor 99.75%
    Sulforaphane is an orally active inducer of the Keap1/Nrf2/ARE pathway. Sulforaphane promotes the transcription of tumor-suppressing proteins and effectively inhibits the activity of HDACs. Through the activation of the Keap1/Nrf2/ARE pathway and further induction of HO-1 expression, Sulforaphane protects the heart. Sulforaphane suppresses high glucose-induced pancreatic cancer through AMPK-dependent signal transmission. Sulforaphane exhibits both anticancer and anti-inflammatory properties.
    Sulforaphane
  • HY-13205
    Belnacasan
    		Inhibitor 99.99%
    Belnacasan (VX-765) is an orally bioactive proagent of VRT-043198, which is a potent and selective inhibitor of IL-converting enzyme (ICE)/caspase-1 with Kis of 0.8 nM and less than 0.6 nM for caspase-1 and caspase-4, respectively. Belnacasan (VX-765) inhibits the release of LPS-induced IL-1β and IL-18 by human PBMCs with an IC50 of ~0.7 μM.
    Belnacasan
  • HY-16658
    Z-VAD(OMe)-FMK
    		Inhibitor 98.20%
    Z-VAD(OMe)-FMK (Z-Val-Ala-Asp(OMe)-FMK) is a cell-permeable and irreversible pan-caspase inhibitor. Z-VAD(OMe)-FMK is an ubiquitin carboxy-terminal hydrolase L1 (UCHL1) inhibitor. Z-VAD(OMe)-FMK irreversibly modifies UCHL1 by targeting the active site of UCHL1.
    Z-VAD(OMe)-FMK
  • HY-W269593
    Perfluorodecanoic acid
    		Inhibitor ≥98.0%
    Perfluorodecanoic acid (PFDA) is a perfluoroalkyl substance (PFAS). Perfluorodecanoic acid induces weight loss and increases liver weight and lipid content in mice. Perfluorodecanoic acid also reduces mRNA expression of the genes encoding IL-1β, IL-18, and cellular inhibitor of apoptosis 2 (cIAP2), as well as caspase-1, -3, and -7 in mouse liver.
    Perfluorodecanoic acid
  • HY-171767
    SK2188
    		Inducer
    SK2188 is a highly efficient and selective PROTAC degrader targeting AURKA (DC50 = 3.9 nM). SK2188 induces DNA damage and cell apoptosis. SK2188 indirectly degrades MYCN, inhibits tumor cell proliferation, and provides insights into the study of MYCN-amplified neuroblastoma (Pink: AURKA ligand: MK-5108 (HY-13252); Blue: Thalidomide (HY-14658); Black: Linker: Amino-PEG4-alcohol (HY-W008005)).
    SK2188
  • HY-W750342
    Tryptophol-d4
    		Inhibitor 99.97%
    Tryptophol-d4 (Indole-3-ethanol-d4) is the deuterium labeled Tryptophol (HY-W010155). Tryptophol is an aromatic alcohol and secondary metabolite produced by microorganisms. Tryptophol induces apoptosis and cleavage of caspase-8. Tryptophol inhibits Cunninghamella blakesleeana biofilm. Tryptophol has anti-phage infection, biofilm formation regulation, anti-inflammatory, hemolytic, sleep induction, temperature change, seizure susceptibility and immune regulation activities. Tryptophol is used in the research of African trypanosomiasis, sleep disorders, epilepsy.
    Tryptophol-d<sub>4</sub>
  • HY-B1081A
    Oxidopamine hydrobromide
    		Activator 98.14%
    Oxidopamine (6-OHDA) hydrobromide is an antagonist of the neurotransmitter dopamine. Oxidopamine hydrobromide is a widely used neurotoxin and selectively destroys dopaminergic neurons. Oxidopamine hydrobromide promotes COX-2 activation, leading to PGE2 synthesis and pro-inflammatory cytokine IL-1β secretion. Oxidopamine hydrobromide can be used for the research of Parkinson’s disease (PD), attention-deficit hyperactivity disorder (ADHD), and Lesch-Nyhan syndrome.
    Oxidopamine hydrobromide
  • HY-100573
    Necrosulfonamide
    		Inhibitor 99.47%
    Necrosulfonamide is a MLKL and Gasdermin D (GSDMD) inhibitor, capable of separately inhibiting necroptosis and pyroptosis of cells. Necrosulfonamide does not affect the activation of upstream signals, but specifically inhibits the downstream executor oligomerization step. Necrosulfonamide reduces the expression of the key kinases NLRP3 and caspase-1 involved in necroptosis and pyroptosis, activate the Nrf2 pathway and the downstream antioxidant enzymes, and also downregulates a variety of inflammatory factors. Necrosulfonamide plays significant roles in various diseases such as neurodegenerative diseases (such as Parkinson’s disease), tissue damage and ischemia-reperfusion injury, inflammatory bowel disease, osteoarthritis and fracture repair, and hair loss by regulating two important programmed necrosis pathways.
    Necrosulfonamide
  • HY-12466
    Z-DEVD-FMK
    		Inhibitor ≥98.0%
    Z-DEVD-FMK is a specific and irreversible caspase-3 inhibitor with an IC50 of 18 μM.
    Z-DEVD-FMK
  • HY-19696
    Tauroursodeoxycholate
    		Inhibitor 99.93%
    Tauroursodeoxycholate (Tauroursodeoxycholic acid) is an orally active endoplasmic reticulum (ER) stress inhibitor. Tauroursodeoxycholate significantly reduces expression of apoptosis molecules, such as caspase-3 and caspase-12. Tauroursodeoxycholate also inhibits ERK.
    Tauroursodeoxycholate
  • HY-14654
    Aspirin
    		Activator 99.90%
    Aspirin (Acetylsalicylic acid) is an orally active, potent and irreversible inhibitor of cyclooxygenase COX-1 and COX-2, with IC50 values of 5 and 210 μg/mL, respectively. Aspirin induces apoptosis. Aspirin inhibits the activation of NF-κB. Aspirin also inhibits platelet prostaglandin synthetase, and can prevent coronary artery and cerebrovascular thrombosis.
    Aspirin
  • HY-10396
    Emricasan
    		Inhibitor 99.81%
    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
  • HY-B1081
    Oxidopamine hydrochloride
    		Activator 99.91%
    Oxidopamine (6-OHDA) hydrochloride is an antagonist of the neurotransmitter dopamine. Oxidopamine hydrochloride is a widely used neurotoxin and selectively destroys dopaminergic neurons. Oxidopamine hydrochloride promotes COX-2 activation, leading to PGE2 synthesis and pro-inflammatory cytokine IL-1β secretion. Oxidopamine hydrochloride can be used for the research of Parkinson’s disease (PD), attention-deficit hyperactivity disorder (ADHD), and Lesch-Nyhan syndrome.
    Oxidopamine hydrochloride
  • HY-N0171A
    Beta-Sitosterol (purity>98%)
    		99.74%
    Beta-Sitosterol (purity>98%) is orally active. Beta-Sitosterol exhibits multiple activities, including anti-inflammatory, anticancer, antioxidant, antimicrobial, antidiabetic, antioxidant enzyme, and analgesic. Beta-Sitosterol inhibits inflammation and impaired adipogenesis in bovine mammary epithelial cells by reducing levels of ROS, TNF-α, IL-1β, and NF-κB p65 and restoring the activity of the HIF-1α/mTOR signaling pathway. Beta-Sitosterol induces apoptosis in cancer cells through ROS-mediated mitochondrial dysregulation and p53 activation. Beta-Sitosterol exerts its anticancer effects in cancer cells by activating caspase-3, caspase-8, and caspase-9, mediating PARP inactivation, MMP loss, altered Bcl-2-Bax ratio, and cytochrome c release. Beta-Sitosterol modulates macrophage polarization and reduces rheumatoid inflammation in mice. Beta-Sitosterol inhibits tumor growth in multiple mouse cancer models. Beta-Sitosterol can be used in the research of arthritis, lung cancer, breast cancer and other cancers, diabetes, etc.
    Beta-Sitosterol (purity>98%)
  • HY-101297
    Z-IETD-FMK
    		Inhibitor ≥98.0%
    Z-IETD-FMK (Z-IE(OMe)TD(OMe)-FMK) is a selective and cell permeable caspase-8 inhibitor. Z-IETD-FMK is also a granzyme B inhibitor.
    Z-IETD-FMK
  • HY-16990
    Ac-YVAD-cmk
    		Inhibitor 98.94%
    Ac-YVAD-cmk (Caspase-1 Inhibitor II) is a selective caspase-1 (IL-1beta converting enzyme, ICE)) inhibitor with neuroprotective and anti-inflammatory effects. Ac-YVAD-cmk effectively suppresses the expression of IL-1β and IL-18. Ac-YVAD-cmk inhibits pyroptosis in many diseases.
    Ac-YVAD-cmk
  • HY-13594
    Chlorin e6
    		98.49%
    Chlorin e6 is a photosensitizer and has strong absorption peaks at wavelength of 402 and 662 nm, as well as exhibiting intense fluorescence at 668 nm. Chlorin e6 has antimicrobial efficacy and anticancer activity. Chlorin e6 induces cell apoptosis via caspase-3 activation and can be used for the research of cancer.
    Chlorin e6
  • HY-121320
    Raptinal
    		Activator ≥98.0%
    Raptinal, a agent that directly activates caspase-3, initiates intrinsic pathway caspase-dependent apoptosis. Raptinal is able to rapidly induce cancer cell death by directly activating the effector caspase-3, bypassing the activation of initiator caspase-8 and caspase-9.
    Raptinal
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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