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-Y0148R
    10-Hydroxydecanoic acid (Standard)
    		Inhibitor
    10-Hydroxydecanoic acid (Standard) is the analytical standard of 10-Hydroxydecanoic acid. This product is intended for research and analytical applications. 10-Hydroxydecanoic acid (10-HDAA) is a saturated fatty acid derived from 10-hydroxy-trans-2-decenoic acid, which can be isolated from royal jelly. 10-Hydroxydecanoic acid exhibits various biological activities, including anti-inflammatory, insecticidal, anti-malarial, and anti-Leishmania properties, as well as enhancing antigen-specific immune responses. The anti-inflammatory effects of 10-Hydroxydecanoic acid are primarily mediated by inhibiting the activation of NF-κB and the translation of interferon regulatory factor 1 (IRF-1), which reduces the production of interleukin 6 (IL-6) and nitric oxide (NO) in inflammatory cells. Additionally, 10-Hydroxydecanoic acid alleviates neuroinflammatory responses through the p53-autophagy pathway and the p53-NLRP3 pathway. Finally, 10-Hydroxydecanoic acid enhances antigen-specific immune responses by promoting the effective uptake of antigens by microfold cells[1][2][3][4][5].
    10-Hydroxydecanoic acid (Standard)
  • HY-136778
    INH2BP
    		Modulator
    INH2BP is a poly(ADP-ribose) polymerase (PARP) inhibitor with antioxidant and anti-apoptotic activities. INH2BP reduces the production of intracellular reactive oxygen species (ROS), modulates the expression of apoptosis-related proteins such as Bax, Bcl-2 and cleaved caspase-3 and enhances cell survival through the activation of the ERK1/2 and p38 MAPK signaling pathways. INH2BP is promising for research of cardiovascular diseases.
    INH2BP
  • HY-120339
    STK899704
    		Activator
    STK899704 is a tubulin polymerization inhibitor. STK899704 exhibits broad-spectrum inhibitory activity against various cancer cell lines with IC50 values ​​ranging from 0.2 to 1.0 μM. STK899704 disrupts the mitotic spindle structure, inducing G2/M phase cell cycle arrest. STK899704 inhibits the migration ability of HT29 cells by downregulating the FAK-MEK-ERK signaling pathway, thereby suppressing the expression and activity of MMP-2 and MMP-9. STK899704 activates caspase-3/7/8/9, leading to PARP cleavage and inducing apoptosis. STK899704 induces cellular senescence through the p53 pathway. STK899704 can be used in research on skin cancer, lung cancer, colon cancer, and other cancers.
    STK899704
  • HY-181442
    CK2-TN03
    		Activator 98.02%
    CK2-TN03 is an ATP-competitive casein kinase 2 (CK2) inhibitor, with an IC50 of 165 nM and a Ki of 20 nM. CK2-TN03 inhibits CK2-mediated survivin activation and reduces CK2-dependent phosphorylation levels of BRD4/MYCN and AKT1. CK2-TN03 exerts anti-neuroblastoma effects by inhibiting survivin, leading to mitotic catastrophe and apoptosis of cancer cells. CK2-TN03 can be used in studies related to neuroblastoma.
    CK2-TN03
  • HY-179157
    MA203
    		Activator
    MA203 is a highly efficient and selective PROTAC degrader targeting CHK1. MA203 accelerates CRBN-dependent proteasomal degradation of CHK1 in solid tumor-derived cells and acute leukemia cells. MA203 induces DNA replication stress. MA203 blocks cell cycle progression and triggers tumor cell apoptosis. MA203 does not damage healthy differentiated and primitive hematopoietic cells, stromal cells, and retinal epithelial cells. MA203 can be used for the study of CHK1-dependent cancers.
    MA203
  • HY-N12669
    Curcumin monoglucoside
    		Inhibitor
    Curcumin monoglucoside is a flavonoid derivative possessing antioxidant, anti-apoptotic, neuroprotective effects, and antibacterial activity. Curcumin monoglucoside can be used in research on Parkinson's disease.
    Curcumin monoglucoside
  • HY-N7719R
    Oosporein (Standard)
    		Activator
    Oosporein (Standard) is the analytical standard of Oosporein (HY-N7719). This product is intended for research and analytical applications. Oosporein is a microbial metabolite and a red crystalline toxin produced by various fungi. Oosporein can promote the reproduction of fungi in host bodies by inhibiting insect immunity, and possesses multiple activities such as antibacterial, antiviral (HSV), and insecticidal effects. Oosporein can inhibit plant growth. In addition, Oosporein can also induce apoptosis, cell membrane damage, oxidative stress, and mitochondrial damage. Oosporein has certain antitumor activity.
    Oosporein (Standard)
  • HY-N1988R
    Cucurbitacin IIa (Standard)
    		Activator
    Cucurbitacin IIa (Hemslecin A) (Standard) is the analytical standard for Cucurbitacin IIa (HY-N1988). This product is used for research and analytical applications. Cucurbitacin IIa is an orally active, blood-brain barrier-penetrating EGFR inhibitor with an IC50 of 1.455 nM for human EGFR. Cucurbitacin IIa induces caspase-3 dependent cell apoptosis, downregulates survivin expression, enhances autophagy levels, disrupts the actin cytoskeleton through actin aggregation, blocks the cell cycle at the G2/M phase, and inhibits the EGFR-MAPK signaling pathway to exert anti-inflammatory activity. Cucurbitacin IIa can be used in research on inflammatory-related diseases, depression, and non-small cell lung cancer and other cancers.
    Cucurbitacin IIa (Standard)
  • HY-132591C
    Inclisiran sodium scrambled negative control
    		Inhibitor
    Inclisiran sodium scrambled negative control is the sequence scrambled negative control of Inclisiran sodium.
    Inclisiran sodium scrambled negative control
  • HY-175010
    STAT3-IN-44
    		Agonist
    STAT3-IN-44 is a potent STAT3 inhibitor with IC50s of 1.84 (C6 cells) and 4.81 μM (A549 cells). STAT3-IN-44 inhibits STAT3 phosphorylation, downregulates Bcl-2, and upregulates Caspase-3 to promote late-stage apoptosis. STAT3-IN-44 significantly suppresses tumor cell proliferation and migration. STAT3-IN-44 can be used for the study of cancers such as glioma and lung cancer.
    STAT3-IN-44
  • HY-P5955
    Ac-AAVALLPAVLLALLAP-LEVD-CHO
    		Inhibitor
    Ac-AAVALLPAVLLALLAP-LEVD-CHO is a cell-permeable caspase-4 inhibitor that has antitumor activity.
    Ac-AAVALLPAVLLALLAP-LEVD-CHO
  • HY-RS01970
    Casp9 Mouse Pre-designed siRNA Set A
    		Inhibitor

    Casp9 Mouse Pre-designed siRNA Set A contains three designed siRNAs for Casp9 gene (Mouse), as well as a negative control, a positive control, and a FAM-labeled negative control.
    Casp9 Mouse Pre-designed siRNA Set A
  • HY-P10326
    Z-ATAD-FMK
    		Inhibitor
    Z-ATAD-FMK is an inhibitor of caspase-12. Z-ATAD-FMK is an inhibitor of caspase-12. Z-ATAD-FMK prevents endoplasmic reticulum stress-mediated apoptosis by inhibiting the activity of caspase-12 and reducing the activity of caspase-9.
    Z-ATAD-FMK
  • HY-144791
    Bcl-2-IN-6
    		Activator
    Bcl-2-IN-6 (compound 10) 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 20.91, 22.30, 42.29, and 48.00 μM against MCF-7, LoVo, HepG2, and A549 cell lines, respectively.
    Bcl-2-IN-6
  • HY-143265
    Topoisomerase I inhibitor 2
    		Inducer
    Topoisomerase I inhibitor 2 (ZML-8) is a highly selective inhibitor of DNA topoisomerase I (Top1). Topoisomerase I inhibitor 2 inhibits Top1 activity and results DNA damage. Topoisomerase I inhibitor 2 blocks G2/M phase and induces apoptosis, exhibits anti-tumor effect.
    Topoisomerase I inhibitor 2
  • HY-178099
    Apoptosis inducer 45
    		Agonist
    Apoptosis inducer 45 is an apoptosis inducer. Apoptosis inducer 45 is cytotoxically active against the MCF-7 cell line. Apoptosis inducer 45 elicits MCF-7 cell apoptosis via the mitochondrial pathway (increases the Bax/Bcl-2 ratio) by activating cleavage of caspase-9, thereby inducing the fragmentation of DNA repair protein PARP. Apoptosis inducer 45 also can induce caspase-8 cleavage, subsequently initiating cleavage of caspase-3 and its downstream protein PARP to culminate in the extrinsic apoptosis. Apoptosis inducer 45 can be used in the research of breast cancer.
    Apoptosis inducer 45
  • HY-P1333A
    Dynorphin A TFA
    		Activator
    Dynorphin A TFA is an endogenous opioid peptide involved in inhibitory neurotransmission in the central nervous system (CNS). Dynorphin A TFA is a highy potent kappa opioid receptor (KOR) agonist, and is also an agonist for other opioid receptors, such as mu (MOR) and delta (DOR). Dynorphin A TFA can induce neuronal death, and can be used in the research of neurological disease.
    Dynorphin A TFA
  • HY-181725
    Topoisomerase I-IN-20
    		Activator
    Topoisomerase I-IN-20 is a Topoisomerase I inhibitor. Topoisomerase I-IN-20 disrupts DNA synthesis and transcription, thereby inhibiting the proliferation and migration of cancer cells. Topoisomerase I-IN-20 induces S-phase cell cycle arrest and mitochondria-mediated Apoptosis in cancer cells, which is characterized by upregulated expression of p53, Bax, caspase-3 and caspase-9, along with downregulated expression of Bcl-2. Topoisomerase I-IN-20 increases intracellular ROS levels. Topoisomerase I-IN-20 is applicable to lung cancer-related research.
    Topoisomerase I-IN-20
  • HY-118304A
    AKN-028 TFA
    		Activator
    AKN-028 TFA, a novel tyrosine kinase (TK) inhibitor, is a potent, orally active FMS-like receptor tyrosine kinase 3 (FLT3) inhibitor with an IC50 value of 6 nM. AKN-028 TFA inhibits FLT3 autophosphorylation. AKN-028 TFA induces dose-dependent cytotoxic response (mean IC50=1 μM). AKN-028 TFA induces apoptosisby activation of caspase 3. AKN-028 TFA can be used in research of acute myeloid leukemia (AML).
    AKN-028 TFA
  • HY-182269
    Cathepsin-IN-5
    Cathepsin-IN-5 is a cathepsin inhibitor with IC50 values of 6.2 μM and 81 nM for cathepsin L and cathepsin S. Cathepsin-IN-5 inhibits cancer cells proliferation, induces apoptosis, reduces growth of hepatocellular tumors in mouse models, and modulates expression of genes linked to cell death, cell proliferation, and cellular processes. Cathepsin-IN-5 can be used for the research of hepatocellular carcinoma.
    Cathepsin-IN-5
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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