1. Signaling Pathways
  2. Apoptosis
  3. Caspase

Caspase

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.

Cat. No. Product Name Effect Purity Chemical Structure
  • HY-182324
    TrxR2-IN-1
    Activator
    TrxR2-IN-1 is a thioredoxin reductase 2 (TrxR2) inhibitor with an IC50 value of 0.83 μM. TrxR2-IN-1 accumulates in mitochondria, impairs mitochondrial function and membrane potential, increases reactive oxygen species (ROS) levels, activates ASK1-mediated caspase-dependent apoptosis (apoptosis), induces G2/M cell cycle arrest, and inhibits cancer cell migration. TrxR2-IN-1 can be used in the research of hepatocellular carcinoma.
    TrxR2-IN-1
  • HY-N16535
    Stigmalactam
    Activator
    Stigmalactam is an aristolactam-type alkaloid extracted from Orophea enterocarpa with anticancer effects. Stigmalactam induces apoptosis via the mitochondrial pathway, with the activation of caspase-3/9, and a decrease in mitochondrial membrane potential (MTP). Stigmalactam exhibits antioxidant activity by decreasing ROS production. Stigmalactam can be used for liver and breast cancer research.
    Stigmalactam
  • HY-182044
    MRTX849-amide-C4-(o)-carborane
    Activator
    MRTX849-amide-C4-(o)-carborane is a KRASG12C inhibitor with mutation selectivity for cells expressing KRASG12C. MRTX849-amide-C4-(o)-carborane shows low intrinsic cytotoxicity in cancer cells. MRTX849-amide-C4-(o)-carborane covalently binds to Cys12 of KRASG12C, recruits Hsp70, promotes ubiquitination, and induces proteasome-dependent degradation of the target protein. MRTX849-amide-C4-(o)-carborane inhibits the activity of the downstream ERK signaling pathway and induces apoptosis signaling in cancer cells. MRTX849-amide-C4-(o)-carborane is applicable for the research of KRASG12C-positive cancers.
    MRTX849-amide-C4-(o)-carborane
  • HY-134567
    Ac-VDVAD-CHO
    Inhibitor
    Ac-VDVAD-CHO is a caspase-2/3 inhibitor (IC50: 46 and 15 nM).
    Ac-VDVAD-CHO
  • HY-P4535
    Ac-Trp-Glu-His-Asp-Aldehyde
    Inhibitor
    Ac-Trp-Glu-His-Asp-Aldehyde is a potent and selective caspase-1 inhibitor with a Ki value of 56 pM.
    Ac-Trp-Glu-His-Asp-Aldehyde
  • HY-RS01951
    Casp2 Rat Pre-designed siRNA Set A
    Inhibitor

    Casp2 Rat Pre-designed siRNA Set A contains three designed siRNAs for Casp2 gene (Rat), as well as a negative control, a positive control, and a FAM-labeled negative control.

    Casp2 Rat Pre-designed siRNA Set A
  • HY-178351
    HDAC6-IN-67
    Inhibitor
    HDAC6-IN-67 is a selective HDAC6 inhibitor (IC50 = 17.15 nM) that exhibits 19-fold selectivity over HDAC1. HDAC6-IN-67 selectively inhibits HDAC6 by interacting with Ser531 and His614. HDAC6-IN-67 induces apoptosis by inducing the cleavage of caspases 9, 8, 3, and PARP, upregulating Bax expression, and downregulating Bcl-2 expression. HDAC6-IN-67 effectively induces the acetylation of α-tubulin, without affecting histone H3 acetylation in MCF-7/ADR cells. HDAC6-IN-67 can be used for the study of breast cancer.
    HDAC6-IN-67
  • HY-N3000A
    6-Methoxydihydrosanguinarine hydrochloride
    Activator
    6-Methoxydihydrosanguinarine hydrochloride is an alkaloid with activity across multiple cancer cell types. 6-Methoxydihydrosanguinarine hydrochloride activates IRE1/JNK signaling, blocks Akt/mTOR and PI3K/AKT/mTOR pathways, reduces expression of Cdc25C, CyclinB1, Cdc2, YAP/TAZ, Survivin, GPX4, and EGFR, upregulates IRE1 and DR5, and activates JNK and caspases. 6-Methoxydihydrosanguinarine hydrochloride induces apoptosis, G2/M phase arrest, DNA damage, ROS generation, lipid peroxidation, ferroptosis, autophagy, and suppresses cancer cell growth. 6-Methoxydihydrosanguinarine hydrochloride disruptes the biofilm formation of Candida albicans (C. albicans). 6-Methoxydihydrosanguinarine hydrochloride can be used for the research of non-small cell lung cancer, hepatocellular carcinoma, melanoma, colon carcinoma, ovarian cancer and breast cancer.
    6-Methoxydihydrosanguinarine hydrochloride
  • HY-170967
    IPH10
    IPH10 is an anti-cancer agent that exhibits a strong anti-tumor effect in vivo without hepatic and renal toxicity. IPH10 can significantly increase the content of ROS, decrease the mitochondrial membrane potential, and induce apoptosis in tumor cells.
    IPH10
  • HY-N7569
    Demethoxyfumitremorgin C
    Activator
    Demethoxyfumitremorgin C is a secondary metabolite of the marine fungus, Aspergillus fumigatus. Demethoxyfumitremorgin C induces prostate cancer cell apoptosis. Demethoxyfumitremorgin C activates caspase-3, -8, and -9, leading to PARP/ cleavage.
    Demethoxyfumitremorgin C
  • HY-W011254
    Ac-VAD-CHO
    Inhibitor
    Ac-VAD-CHO (Ac-Val-Ala-Asp-CHO) is a pan-caspase inhibitor. Ac-VAD-CHO inhibits dissipation of MMP and cytochrome c release in hypoxia-exposed cells.
    Ac-VAD-CHO
  • HY-182957
    MNK/PIM-IN-2
    Modulator
    MNK/PIM-IN-2 is a Mnk/Pim kinase inhibitor with an IC50 of 32 nM for Mnk1, 3 nM for Mnk2, and 37 nM for Pim1. MNK/PIM-IN-2 reduces the levels of p-eIF4E and p-4EBP1. MNK/PIM-IN-2 induces cell cycle arrest, apoptosis (apoptosis) and exerts antiproliferative effects in leukemia cells. MNK/PIM-IN-2 can be used in studies related to leukemia.
    MNK/PIM-IN-2
  • HY-120105
    NSC666715
    Activator
    NSC666715 is a DNA polymerase β (Pol-β) inhibitor. NSC666715 directly and specifically interacts with Pol-β, interferes with its binding to damaged DNA, blocks its dRP lyase activity, and inhibits Pol-β-mediated SN- and LP-BER. NSC666715 induces AP site accumulation and S-phase cell cycle arrest, and triggers senescence and apoptosis (apoptosis) via the p53/p21 pathway in colorectal cancer cells. NSC666715 enhances TMZ (HY-17364)-induced DNA damage, senescence and apoptosis, and potentiates the cytotoxicity of TMZ. NSC666715 inhibits tumor growth in colon cancer xenograft models. NSC666715 can be used in research related to colorectal cancer.
    NSC666715
  • HY-RS01950
    Casp2 Mouse Pre-designed siRNA Set A
    Inhibitor

    Casp2 Mouse Pre-designed siRNA Set A contains three designed siRNAs for Casp2 gene (Mouse), as well as a negative control, a positive control, and a FAM-labeled negative control.

    Casp2 Mouse Pre-designed siRNA Set A
  • HY-P4890
    Relaxin H3 (human)
    Inhibitor
    Relaxin H3 (human) is a relaxin peptide with anti-inflammatory, anti-apoptotic, anti-pyroptotic, anti-migratory, protective and anti-fibrotic activities. Relaxin H3 (human) acts on RXFP1 to generate cAMP and reduce the levels of ATP and ROS. Relaxin H3 (human) inhibits renal inflammatory pyroptosis (pyroptosis), NLRP3 inflammasome activation, caspase-1 activation, IL-1β/IL-18 secretion, collagen synthesis, TGF-β1 signaling pathway, Smad2 phosphorylation, myofibroblast differentiation, TIMP expression, and HRMEC migration. Relaxin H3 (human) activates AMPK, upregulates MFN2 expression, improves mitochondrial quality control and membrane potential, inhibits apoptosis (apoptosis) and pyroptosis, restores retinal ultrastructure, and reverses excessive left ventricular collagen expression. Relaxin H3 (human) can be used in studies related to kidney stones, nephrocalcinosis, diabetic cardiomyopathy, fibrotic cardiomyopathy, and diabetic retinopathy.
    Relaxin H3 (human)
  • HY-N11643
    Ganoderic acid Mk
    Activator
    Ganoderic acid Mk (GA-Mk) is a triterpenoid acid, that can be isolated from the mycelia of Ganoderma lucidum. Ganoderic acid Mk is efficiently anti-proliferative and can induce apoptosis of HeLa cells by mitochondria-mediated pathway. Ganoderic acid Mk can be used for cervical cancer research.
    Ganoderic acid Mk
  • HY-N0361S
    Dihydrocapsaicin-d3
    Inhibitor
    Dihydrocapsaicin-d3 is the deuterium labeled Dihydrocapsaicin (HY-N0361). Dihydrocapsaicin, a capsaicin, is a potent and selective TRPV1 (transient receptor potential vanilloid channel 1) agonist. Dihydrocapsaicin reduces AIF, Bax, and Caspase-3 expressions, and increased Bcl-2, Bcl-xL and p-Akt levels. Dihydrocapsaicin enhances the hypothermia-induced neuroprotection following ischemic stroke via PI3K/Akt regulation in rat.
    Dihydrocapsaicin-d<sub>3</sub>
  • HY-P5834A
    Boc-AEVD-CHO TFA
    Inhibitor
    Boc-AEVD-CHO TFA is a Caspase 8 inhibitor. Boc-AEVD-CHO TFA significantly increases the frequencies of Nocodazole (HY-13520) or methyl methane sulfonate (MMS) induced micronuclei (MN) and micronucleated binucleates (MNCB) in PBMC by inhibiting cell apoptosis. Boc-AEVD-CHO TFA can be used for immune and inflammatory diseases research.
    Boc-AEVD-CHO TFA
  • HY-P3476
    Mca-VDQVDGW-Lys(Dnp)-NH2
    Substrate
    Mca-VDQVDGW-Lys(Dnp)-NH2 is a fluorogenic substrate of caspase-7. Mca-VDQVDGW-K(Dnp)-NH2 can be used to quantify caspase-7 activity.
    Mca-VDQVDGW-Lys(Dnp)-NH2
  • HY-RS01955
    CASP4 Human Pre-designed siRNA Set A
    Inhibitor

    CASP4 Human Pre-designed siRNA Set A contains three designed siRNAs for CASP4 gene (Human), as well as a negative control, a positive control, and a FAM-labeled negative control.

    CASP4 Human Pre-designed siRNA Set A
Cat. No. Product Name / Synonyms Species Source
Cat. No. Product Name / Synonyms Application Reactivity

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.

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