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-P1008A
    Z-VDVA-(DL-Asp)-FMK
    Z-VDVA-(DL-Asp)-FMK is a Z-VDVAD-FMK derivative. Z-VDVAD-FMK (HY-P1008) is a special inhibitor of caspase-2.
    Z-VDVA-(DL-Asp)-FMK
  • HY-W011683S
    2'-Deoxyadenosine monohydrate-1′-13C
    		Activator
    2'-Deoxyadenosine monohydrate-1′-13C is the 13C labeled 2'-Deoxyadenosine monohydrate (HY-W011683). 2′-Deoxyadenosine monohydrate is an adenine nucleoside that inhibits glucose-stimulated insulin release. 2′-Deoxyadenosine monohydrate inhibits glucose-stimulated increases seen in islet cyclic AMP (cAMP) accumulation. 2'-Deoxyadenosine monohydrate activates caspase-3 and promotes apoptosis. 2'-Deoxyadenosine monohydrate inhibits the activity of S-adenosyl-L-homocysteine hydrolase (SAHH). 2'-Deoxyadenosine monohydrate inhibits the growth of various cells. 2'-Deoxyadenosine monohydrate has an anticancer effect on colon cancer.
    2'-Deoxyadenosine monohydrate-1′-<sup>13</sup>C
  • HY-RS01947
    Casp12 Rat Pre-designed siRNA Set A
    		Inhibitor

    Casp12 Rat Pre-designed siRNA Set A contains three designed siRNAs for Casp12 gene (Rat), as well as a negative control, a positive control, and a FAM-labeled negative control.
    Casp12 Rat Pre-designed siRNA Set A
  • HY-120257
    IDN-1965
    		Inhibitor
    IDN-1965 is an irreversible, broad-spectrum caspase inhibitor. IDN-1965 prevents downstream apoptotic events (such as DNase activation) and significantly delays cytochrome c release by inhibiting caspase activity. IDN-1965 significantly delayed death in mice with cardiomyocyte apoptosis. IDN-1965 completely prevents left ventricular dilation, systolic dysfunction, and fibrosis in mice with dilated cardiomyopathy. IDN-1965 can be used to study apoptosis-related diseases such as heart failure and the mechanisms of apoptosis initiation.
    IDN-1965
  • HY-N4323R
    14-Deoxyandrographolide (Standard)
    		Inhibitor
    14-Deoxyandrographolide (Standard) is the analytical standard of 14-Deoxyandrographolide. 14-Deoxyandrographolide is a diterpene with calcium channel blocking activity and acts as a uterine smooth muscle relaxant. 14-Deoxyandrographolide stimulates the release of nitric oxide (NO) in endothelial cells. 14-Deoxyandrographolide gradually desensitizes liver cells to TNF-α mediated apoptosis by inducing the release of TNFRSF1A.
    14-Deoxyandrographolide (Standard)
  • HY-W713297
    Moroxydine hydrochloride-d8
    		Inhibitor
    Moroxydine hydrochloride-d8 (ABOB hydrochloride-d8) is the deuterium labeled Moroxydine (ABOB) hydrochloride (HY-B0420A). Moroxydine hydrochloride is a broad-spectrum agent with multi-antiviral activities against DNA and RNA viruses, including influenza virus, herpes simplex, varicella zoster, measles, mumps disease, hepatitis C virus, etc. Moroxydine hydrochloride exhibits excellent antiviral activity and shows low cytotoxicity to cells infected by dsRNA viruses (grass carp reovirus, GCRV) and large DNA viruses (giant salamander iridovirus, GSIV). Moroxydine hydrochloride blocks the GCRV-induced cytopathic effects and eliminates nucleocapsids in ctenopharyngodon idella kidney (CIK) cells to keep the normal morphological structure. Moroxydine hydrochloride significantly inhibits the apoptosis, the caspase 3 activity, Bax expression and down-regulates Bcl-2 levels[1][2][3].
    Moroxydine hydrochloride-d<sub>8</sub>
  • HY-155759
    HMGB1-IN-2
    		Inhibitor
    HMGB1-IN-2 (compound 15) is an inhibitor of highly conserved nuclear protein (HMGB1), showing NO inhibitory effect with IC50 value of 20.2 μM in RAW264.7 cells. HMGB1-IN-2 (30 μM) decreases the level of IL-1 β, TNF-α, caspase-1 p20, inhibits the phosphorylation of NF-κB p65, exhibits anti-apoptotic activity. HMGB1-IN-2 (15 mg/kg; ip) relives kidney injury in septic acute kidney injury mouse. HMGB1-IN-2 inhibits Huh7 cells and A549 cells with IC50s of 77.0 μM, and 82.0 μM, respectively.
    HMGB1-IN-2
  • HY-P6285
    Z-TPE-2DEVD
    Z-TPE-2DEVD is a specific probe for caspase-3.
    Z-TPE-2DEVD
  • HY-136733
    Ac-DNLD-CHO
    		Inhibitor
    Ac-DNLD-CHO (Ac-Asp-Asn-Leu-Asp-CHO) is a Caspase-3/7 inhibitor (IC50: 9.89, 245 nM respectively; Kiapp: 0.68, 55.7 nM respectively). Ac-DNLD-CHO can be used for research of caspase-mediated apoptosis diseases, such as neurodegenerative disorders and viral infection diseases.
    Ac-DNLD-CHO
  • HY-P991669
    IGN523
    		Agonist
    IGN523 is an anti-CD98 antibody (hCD98, KD = 0.55 nM). IGN523 induces antibody-dependent cell-mediated cytotoxicity (ADCC) activity, lysosomal membrane permeabilization, and inhibition of essential amino acid transport, ultimately leading to caspase-3 and caspase-7-mediated apoptosis of tumor cells. IGN523 inhibits tumor growth in multiple tumor xenograft models. IGN523 is useful in the research of non-small cell lung cancer (NSCLC), acute myeloid leukemia (AML), and other cancers..
    IGN523
  • HY-P2610
    Ac-VEID-pNA
    		Activator
    Ac-VEID-pNA is an artificially synthesized peptide. Ac-VEID-pNA is utilized as substrate for caspase 6, that cleaves the lamin A at the cleavage site of VEID.
    Ac-VEID-pNA
  • HY-175036
    YTHu78
    		Activator
    YTHu78 is a KDM5B PROTAC-type degrader. YTHu78 induces KDM5B degradation via the ubiquitin-proteasome system and triggers apoptosis in MV-4-11 and MM.1S cell lines. YTHu78 exhibits significant antiproliferative activity against a variety of hematological cancer cell lines and can be used to study hematological cancers. (Pink: KDM5B ligand: (HY-116761); Blue: Thalidomide ligand: (HY-14658), Black + Pink: KDM5B ligand + linker: (HY-175145)).
    YTHu78
  • HY-155613
    M867
    		Inhibitor
    M867 is a selective and reversible inhibitor of caspase-3 with an IC50 of 1.4 nM and Ki of 0.7 nM. M867 has anti apoptotic activity.
    M867
  • HY-178955
    EGFR-IN-182
    		Activator
    EGFR-IN-182 (Compound 4) is an EGFR inhibitor with an IC50 value of 199 nM. EGFR-IN-182 inhibits HSP90 and PI3K, with IC50 values of 5.007 and 13.596 μM respectively. EGFR-IN-182 exhibits strong anti-proliferative activity against MCF-7 and MDA-MB-231 cells. EGFR-IN-182 downregulates Cyclin D1, inducing cell cycle arrest; it enhances the activity of caspase-9, inducing cell apoptosis. EGFR-IN-182 downregulates the expressions of ERK and AKT. EGFR-IN-182 can be used for research on breast cancer.
    EGFR-IN-182
  • HY-N0213R
    Peiminine (Standard)
    Peiminine (Standard) is the analytical standard of Peiminine. This product is intended for research and analytical applications. Peiminine is a compound that can be isolated from Bolbostemma paniculatum (Maxim) Franquet (Cucurbitaceae family). Peiminine can induce apoptosis in human hepatocellular carcinoma HepG2 cells through both extrinsic and intrinsic apoptotic pathways. Peiminine has anti-inflammatory, anticancer, anti-osteoporosis, cardioprotective and other activities in many animal models.
    Peiminine (Standard)
  • HY-144792
    Bcl-2-IN-7
    		Activator
    Bcl-2-IN-7 (compound 6) is a potent Bcl-2 (B-cell lymphoma-2) inhibitor. Bcl-2-IN-7 down-regulates the expression of Bcl-2, and increases the expression of p53, Bax, and caspase-7 mRNA. Bcl-2-IN-7 induces cell cycle arrest and apoptosis in breast cancer MCF-7 cells. Bcl-2-IN-7 shows good anticancer activity, with IC50 values of 20.17, 22.64, 45.57, and 51.50 μM against MCF-7, LoVo, HepG2, and A549 cell lines, respectively.
    Bcl-2-IN-7
  • HY-136728
    Ac-YVAD-AOM
    		Inhibitor
    Ac-YVAD-AOM is the inhibitor of caspase-1 that shows antitumor activity.
    Ac-YVAD-AOM
  • HY-W046353R
    2-Methoxycinnamaldehyde (Standard)
    		Activator
    2-Methoxycinnamaldehyde (Standard) is the analytical standard of 2-Methoxycinnamaldehyde. This product is intended for research and analytical applications. 2-Methoxycinnamaldehyde (o-Methoxycinnamaldehyde) is a natural compound that can be isolated from Cinnamomum cassia. 2-Methoxycinnamaldehyde inhibits topoisomerase-I/II and NF-κB signaling pathway, causes mitochondrial dysfunction, induces lysosomal vesiculation, thereby leading to DNA damage and cell apoptosis. 2-Methoxycinnamaldehyde exhibits antitumor effects.
    2-Methoxycinnamaldehyde (Standard)
  • HY-116692
    Apoptosis inducer 34
    		Activator
    Apoptosis inducer 34 (Compound 4) is a small molecule compound that induces apoptosis by directly activating the intrinsic apoptotic pathway. Apoptosis inducer 34 promotes Apaf-1 oligomerization to form mature apoptosomes, thereby activating caspase-9 and caspase-3. It significantly activates the apoptotic pathway in Jurkat cells by enhancing the cytochrome c-dependent apoptotic signaling pathway, inducing PARP cleavage and chromosomal DNA fragmentation. Furthermore, Apoptosis inducer 34 exhibits low toxicity to normal cells, demonstrating potential for selective targeting of cancer cells. Apoptosis inducer 34 is a promising candidate for studying cancer related to apoptotic pathways.
    Apoptosis inducer 34
  • HY-P1169A
    Ac-IETD-AFC TFA
    Ac-IETD-AFC TFA is a synthetic fluorogenic substrate that can be used to specifically detect caspase-8 activity. INDO 1 pentasodium is imbued with the fluorophore AFC (7-amino-4-trifluoromethylcoumarin). When caspase-8 recognizes and cleaves the amide bond following the IETD sequence in this substrate, AFC is released and emits fluorescence (Ex = ~400 nm; Em = ~505 nm).
    Ac-IETD-AFC TFA
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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