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-176860
    NEK7 degrader-1
    		Inhibitor
    NEK7 degrader-1 (Compound 17) is a NEK7 degrader with a DC50 of 0.1  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-RS01962
    CASP7 Human Pre-designed siRNA Set A
    		Inhibitor

    CASP7 Human Pre-designed siRNA Set A contains three designed siRNAs for CASP7 gene (Human), as well as a negative control, a positive control, and a FAM-labeled negative control.
    CASP7 Human Pre-designed siRNA Set A
  • HY-W020050S
    Cystamine-d8 dihydrochloride
    Cystamine-d8 (dihydrochloride） is the deuterium labeled Cystamine (dihydrochloride）. Cystamine (dihydrochloride) is the disulfide form of the free thiol, cysteamine. Cystamine is an orally active transglutaminase (Tgase) inhibitor. Cystamine also has inhibition activity for caspase-3 with an IC50 value of 23.6 μM. Cystamine can be used for the research of severals diseases including Huntington's disease (HD).
    Cystamine-d<sub>8</sub> dihydrochloride
  • HY-168589
    Apoptosis inducer 30
    		Activator
    Apoptosis inducer 30 (Compound 15a) is an anticancer agent. Apoptosis inducer 30 induces MCF-7 cells apoptosis through mitochondrial pathway. Apoptosis inducer 30 induces intracellular reactive oxygen species levels and decreases mitochondrial membrane potential, and blocks the cell cycle in the G0/G1 phase. Apoptosis inducer 30 inhibits cell growth, with an IC50 value of 0.32 μM against MCF-7 cells, and inhibits tumor growth in a mouse model of breast cancer.
    Apoptosis inducer 30
  • HY-N7045R
    Isosilybin B (Standard)
    		Activator
    Isosilybin B (Standard) is the analytical standard of Isosilybin B (HY-N7045). This product is intended for research and analytical applications. Isosilybin B is a flavonolignan. Isosilybin B can be isolated from Silybum marianum. Isosilybin B can regulate cell cycle-related proteins (e.g., reduce cyclins (D3, D1, A, E), Cdk4, Cdk2, Cdc25A), and activate Caspases (Caspase-9 and Caspase-3). Isosilybin B can promote Apoptosis, reduce androgen receptor (AR) and PSA. Isosilybin B has anticancer activity against prostate cancer.
    Isosilybin B (Standard)
  • HY-175548
    Nrf2 activator-21
    		Inhibitor
    Nrf2 activator-21 is a Nrf2 activator with dual antioxidant and neuroprotective properties. Nrf2 activator-21 binds to Keap1 Kelch domain and disrupts Keap1-Nrf2 interactions and activate antioxidant defense mechanisms. Nrf2 activator-21 reduces apoptosis and decreases caspase-3 activity in the hippocampal neurons. Nrf2 activator-21 targets cerebral ischemia/reperfusion injury (CIRI) via Nrf2 pathway activation. Nrf2 activator-21 improves neurological function, alleviates anxiety-like behavior, enhances memory in rats with 2-vessel occlusion (2VO)-induced CIRI. Nrf2 activator-21 can be used for the study of cerebral ischemia/reperfusion injury.
    Nrf2 activator-21
  • HY-169431
    VEGFR-2/AKT-IN-2
    		Activator
    VEGFR-2/AKT-IN-2 (Compound 5) is a VEGFR-2/AKT inhibitor (IC50: 0.061 μM for VEGFRin HepG2 cell). VEGFR-2/AKT-IN-2 reduces total and phosphorylated AKT as well as up-regulates BAX and Caspase-3 and down-regulates Bcl-2 in cells, thereby promoting Apoptosis. VEGFR-2/AKT-IN-2 causes cell cycle arrest in S phase. VEGFR-2/AKT-IN-2 inhibits the growth of human liver tumor cells.
    VEGFR-2/AKT-IN-2
  • HY-176718
    VEGFR-2-IN-69
    		Activator
    VEGFR-2-IN-69 (Compound 5A) is a dual inhibitor of VEGFR-2 and Telomerase, which upregulates the expression of caspase 3, caspase 8 and caspase 9, while downregulating CDK-2, CDK-4 and CDK-6. VEGFR-2-IN-69 exhibits an IC50 of 15.46 µM against HCT116 cells.
    VEGFR-2-IN-69
  • HY-N1970R
    5,7-Dihydroxychromone (Standard)
    		Activator
    5,7-Dihydroxychromone (Standard) is the analytical standard of 5,7-Dihydroxychromone. This product is intended for research and analytical applications. 5,7-Dihydroxychromone, the extract of Cudrania tricuspidata, activates Nrf2/ARE signal and exerts neuroprotective effects against 6-hydroxydopamine (6-OHDA)-induced oxidative stress and apoptosis. 5,7-Dihydroxychromone inhibits the expression of activated caspase-3 and caspase-9 and cleaved PARP in 6-OHDA-induced SH-SY5Y cells.
    5,7-Dihydroxychromone (Standard)
  • HY-N2420R
    Flavokawain A (Standard)
    		Activator
    Flavokawain A is a chalcone compound and an orally active inhibitor of PRMT5 and cytochrome P450. Flavokawain A has anti-inflammatory, anti-tumor, and immunomodulatory effects. Flavokawain A can inhibit the proliferation of tumor cells and induce apoptosis. Flavokawain A can be used in the research of diseases such as bladder cancer.
    Flavokawain A (Standard)
  • HY-158820
    Cosdosiran
    		98.48%
    Cosdosiran is a chemically modified siRNA designed to temporarily inhibit expression of the caspase 2 protein and can be used for the study of nonarteritic anterior ischemic optic neuropathy and other optic neuropathies such as glaucoma that result in the death of retinal ganglion cells.?
    Cosdosiran
  • HY-13721R
    Phenoxodiol (Standard)
    		Activator
    Phenoxodiol (Standard) is the analytical standard of Phenoxodiol. This product is intended for research and analytical applications. Phenoxodiol (Idronoxil), a synthetic analog of Genestein, activates the mitochondrial caspase system, inhibits XIAP (an apoptosis inhibitor), and sensitizes the cancer cells to Fas-mediated apoptosis. Phenoxodiol also inhibits DNA topoisomerase II by stabilizing the cleavable complex. Phenoxodiol induces cell cycle arrest in the G1/S phase of the cell cycle and upregulates p21WAF1 via a p53 independent manner.
    Phenoxodiol (Standard)
  • HY-155402
    Antiproliferative agent-42
    		Inhibitor
    Antiproliferative agent-42 (compound 7m) is a dihydrodipyrrolo compound. Antiproliferative agent-42 showed antiproliferative activity against Panc-1 cell line with an IC50 value of 12.54 μM.
    Antiproliferative agent-42
  • HY-108312
    Ac-VEID-CHO
    		Inhibitor
    Ac-VEID-CHO 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 also inhibits VEIDase activity an IC50 value of 0.49 µM. Ac-VEID-CHO can be used for the research of neurodegenerative conditions including Alzheimer’s and Huntington’s disease.
    Ac-VEID-CHO
  • HY-N0265R
    Asperosaponin VI (Standard)
    		Inhibitor
    Asperosaponin VI (Standard) is the analytical standard of Asperosaponin VI. This product is intended for research and analytical applications. Asperosaponin VI is a saponin component from Dipsacus asper. Asperosaponin VI induces osteoblast differentiation through the BMP-2/p38 and ERK1/2 signaling pathways. Asperosaponin VI protects against hypoxia-induced cardiomyocyte apoptosis by activating the PI3K/Akt and CREB pathways. Additionally, Asperosaponin VI also has antidepressant and wound-healing-promoting activities.
    Asperosaponin VI (Standard)
  • HY-117047
    ALC67
    		Activator
    ALC67 is a cytotoxic thiazolidine compound with an IC50 of approximately 5 μM against liver, breast cancer, colon cancer, and endometrial cancer cell lines. ALC67 induces apoptosis in cancer cells by activating caspase-9 and causing cell cycle arrest at the SubG1/G1 phase, via a pathway that is independent of death receptors. ALC67 can be used in cancer research.
    ALC67
  • HY-171031
    TFGF-18
    		Activator
    TFGF-18 is a GSK-3β inhibitor (IC50: 0.59 μM). TFGF-18 inhibits LPS-induced microglia activation and proinflammatory mediators release via inhibiting GSK-3β and downstream p65/NF-κB signaling. TFGF-18 inhibits neuronal apoptosis and oxidative stress, inhibits expressions of Bax, caspase3 and cleaved-caspase3 and increases the expression of Bcl-2. TFGF-18 has neuroprotection effect, inhibit neuroinflammation and attenuates cognitive impairment.
    TFGF-18
  • HY-W724853
    Dimethyl tetrasulfide
    		Activator
    Dimethyl tetrasulfide (1,4-Dimethyltetrasulfane) is an apoptosis inducer targeting leukemia cells. Dimethyl tetrasulfide exerts cytotoxic effects through the induction of intracellular reactive oxygen species (ROS) production and activation of caspase-3 enzyme. Dimethyl tetrasulfide is promising for research of cancers, such as leukemia.
    Dimethyl tetrasulfide
  • HY-N0876R
    Arenobufagin (Standard)
    Arenobufagin is a natural bufadienolide that can be extracted from toad venom. Arenobufagin can induce apoptosis and autophagy in human hepatocellular carcinoma cells through inhibition of PI3K/Akt/mTOR pathway. Arenobufagin has potent antineoplastic activity against HCC HepG2 cells as well as corresponding multidrug-resistant HepG2/ADM cells. Arenobufagin can inhibit VEGF-mediated angiogenesis through suppression of VEGFR-2 signaling pathway.
    Arenobufagin (Standard)
  • HY-N0346
    4-Methoxycinnamic acid ethyl ester
    		Agonist
    4-Methoxycinnamic acid ethyl ester (Ethyl p-methoxycinnamate) is an orally active natural compound found. 4-Methoxycinnamic acid ethyl ester exerts anti-inflammatory effects by inhibiting cyclooxygenase (COX-1 (IC50 = 1.12 μM) and COX-2 (IC50 = 0.83 μM)), NF-κB (IC50 = 88.7 μM) and cytokine production (TNF-α (IC50 = 96.84 μg/mL) and IL-1β (IC50 = 166.4 μg/mL)). 4-Methoxycinnamic acid ethyl ester inhibits tumor cell proliferation, migration and cancer metabolism and induces apoptosis.4-Methoxycinnamic acid ethyl ester inhibits VEGF expression, thereby inhibiting angiogenesis. 4-Methoxycinnamic acid ethyl ester has a significant inhibitory effect on dengue virus and Mycobacterium tuberculosis. 4-Methoxycinnamic acid ethyl ester has analgesic effects in rats.
    4-Methoxycinnamic acid ethyl ester
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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