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-N0591R
    Dehydrocostus Lactone (Standard)
    Dehydrocostus Lactone (Standard) ((-)-Dehydrocostus lactone (Standard)) is the analytical standard of Dehydrocostus Lactone (HY-N0591). This product is intended for research and analytical applications. Dehydrocostus Lactone is a natural sesquiterpene that can be isolated from Saussurea lappa. Dehydrocostus Lactone has multiple activities such as anti-inflammatory, antibacterial, anti-tumor, and immunomodulatory effects. Dehydrocostus Lactone has an MIC of 2 µg/mL against Mycobacterium tuberculosis. Dehydrocostus Lactone can also inhibit the killing activity of cytotoxic T lymphocytes and induce apoptosis in tumor cells.
    Dehydrocostus Lactone (Standard)
  • HY-14654C
    Aspirin calcium
    		Activator
    Aspirin calcium 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 calcium induces apoptosis. Aspirin calcium inhibits the activation of NF-κB. Aspirin calcium also inhibits platelet prostaglandin synthetase, and can prevent coronary artery and cerebrovascular thrombosis.
    Aspirin calcium
  • HY-P1010A
    Z-LEHD-FMK TFA
    		Inhibitor
    Z-LEHD-FMK TFA is a selective and irreversible inhibitor of caspase-9, protects against lethal reperfusion injury and attenuates apoptosis. Z-LEHD-FMK TFA exhibits the neuroprotective effect in a rat model of spinal cord trauma.
    Z-LEHD-FMK TFA
  • HY-N0361R
    Dihydrocapsaicin (Standard)
    		Inhibitor
    Dihydrocapsaicin (Standard) is the analytical standard of Dihydrocapsaicin. This product is intended for research and analytical applications. 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 (Standard)
  • HY-118522
    TP-110
    		Agonist
    TP-110 is a proteasome inhibitor. TP-110 specifically inhibits the protease-like activity of the 20S proteasome, but does not affect the trypsin-like or peptidyl-glutamyl peptide hydrolysis activity. TP-110 inhibits the NF-κB pathway, activates caspase-8, -9, and -3, and causes PARP cleavage, significantly reducing the levels of cIAP-1 and XIAP. TP-110 causes cell cycle arrest at the G2/M phase and promotes apoptosis of cancer cells. TP-110 can be used in cancer research of prostate cancer and multiple myeloma, etc.
    TP-110
  • HY-B0762R
    Acetyl-L-carnitine hydrochloride (Standard)
    		Inhibitor
    Acetyl-L-carnitine hydrochloride (Standard) is the analytical standard of Acetyl-L-carnitine hydrochloride. This product is intended for research and analytical applications. Acetyl-L-carnitine (O-Acetyl-L-carnitine; ALCAR) hydrochloride is an orally active mitochondrial energy metabolism regulator and neuroprotectant that can penetrate the blood-brain barrier. Acetyl-L-carnitine hydrochloride selectively enters cells and the brain through the organic cation transporter OCTN2. Acetyl-L-carnitine hydrochloride can participate in fatty acid β-oxidation, promote acetylcholine synthesis, regulate mitochondrial function and inhibit oxidative stress as an acetyl donor. Acetyl-L-carnitine hydrochloride exerts its activity by enhancing energy metabolism, protecting neurons and improving synaptic plasticity. Acetyl-L-carnitine hydrochloride is mainly used in the study of neurodegenerative diseases and metabolic disorder-related diseases such as neonatal hypoxic-ischemic brain damage, Alzheimer's disease, and depression.
    Acetyl-L-carnitine hydrochloride (Standard)
  • HY-P2374
    Ac-DMQD-CHO
    		Inhibitor
    Ac-DMQD-CHO is a selective inhibitor for caspase 3, with IC50 of 39 nM. Ac-DMQD-CHO reduces apoptosis, and exhibits neuroprotective efficacy.
    Ac-DMQD-CHO
  • HY-138203
    Z-LE(OMe)TD(OMe)-FMK
    		Inhibitor
    Z-LE(OMe)TD(OMe)-FMK is a selective caspase-8 inhibitor. Z-LE(OMe)TD(OMe)-FMK can inhibit cell apoptosis.
    Z-LE(OMe)TD(OMe)-FMK
  • HY-175332
    Apoptosis inducer 43
    		Inhibitor
    Apoptosis inducer 43 is an apoptosis inducer. Apoptosis inducer 43 can induce apoptosis, SubG0-G1 cell cycle arrest, secondary necrosis, and upregulate caspase-3, p53, and Bax/Bcl-2 expression in HCT116 cells. Apoptosis inducer 43 can inhibit tumor growth in a solid Ehrlich carcinoma (SEC) mouse model. Apoptosis inducer 43 can be used to study cancers such as colon cancer, leukemia, and non-small cell lung cancer.
    Apoptosis inducer 43
  • HY-174984
    VCP/p97 IN-3
    		Activator
    VCP/p97 IN-3 is a VCP/p97 allosteric inhibitor. VCP/p97 IN-3 shows the inhibitory activity against the VCP proteins with an IC50 of 9 nM and the mutant VCP proteins with IC50 of 12 nM (N660K) and 19 nM (V474A/D649A). VCP/p97 IN-3 increases K48-linked ubiquitination and the level of cleaved caspase-3. VCP/p97 IN-3 activates ER-stress and the UPR. VCP/p97 IN-3 inhibits tumor growth in RPMI-8226 cell subcutaneous xenograft mouse models. VCP/p97 IN-3 can be used for the study of multiple myeloma.
    VCP/p97 IN-3
  • HY-125911R
    Gossypin (Standard)
    		Inducer
    Gossypin (Standard) is the analytical standard of Gossypin. This product is intended for research and analytical applications. Gossypin is an orally active flavone isolated from Hibiscus vitifolius. Gossypin has antioxidant, antiinflammatory, anticancer, anticataract, antidiabetic, and hepatoprotective activities. Gossypin inhibits NF-κB and NF-κB-regulated gene expression. Gossypin inhibits AURKA and RSK2. Gossypin inhibits invasion and induces apoptosis. Gossypin can be used for gastric cancer study.
    Gossypin (Standard)
  • HY-175227
    STAT3/NF-κB-IN-1
    		Agonist
    STAT3/NF-κB-IN-1 is a potentSTAT3 and NF-κB inhibitor with IC50s of 5.86 (STAT3) and 4.22 μM (NF-κB) in 4T1 cells. STAT3/NF-κB-IN-1 is able to induce apoptosis via its upregulation on key apoptotic regulators; caspases-3/9, Bax and downregulation of Bcl-2. STAT3/NF-κB-IN-1 exerts considerable anticancer activity against breast cancer cell lines and reduces tumor volume in vivo. STAT3/NF-κB-IN-1 can be used for the study of breast cancer.
    STAT3/NF-κB-IN-1
  • HY-W011683S3
    2'-Deoxyadenosine monohydrate-5′-13C
    		Activator
    2'-Deoxyadenosine monohydrate-5′-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-5′-<sup>13</sup>C
  • HY-149978
    LSD1-IN-26
    		Modulator
    LSD1-IN-26 (compound 12u) is a potent LSD1 inhibitor, with an IC50 of 25.3 nM. LSD1-IN-26 also inhibits MAO-A (IC50=1234.57 nM) and MAO-B (IC50=3819.27 nM). LSD1-IN-26 significantly induces apoptosis in MGC-803 cells. LSD1-IN-26 can be used for gastric cancer research.
    LSD1-IN-26
  • HY-P11108
    RP-182
    		Activator
    RP-182 is a synthetic immunomodulatory peptide that exerts anti-tumor effects by targeting the mannose receptor CD206 (Kd = 8 μM) on the surface of tumor-associated macrophages (TAMs). RP-182 induces a conformational switch of the CD206 receptor, which activates NF-κB signaling and phagocytosis in CD206high TAMs. RP-182 has dual function: activation of canonical NF-κB signaling, triggering TNFα secretion and autocrine activation of the TNF receptor 1 (TNFR1), leading to activation of caspase 8, apoptosis, and cell death. RP-182 is used in pancreatic cancer and melanoma research.
    RP-182
  • HY-178944
    CDC25-IN-1
    		Activator
    CDC25-IN-1 (Compound D11b) is a potent inhibitor of cell division cycle 25 (CDC25) phosphatase. CDC25-IN-1 exerts strong inhibitory effects on leukemia and colorectal cancer cells. CDC25-IN-1 blocks CDC25 mediated CDK1 Tyr15 dephosphorylation, delays G2/M progression, and induces caspase-dependent apoptosis with DNA damage. CDC25-IN-1 can be used for researches of leukemia and colorectal cancer.
    CDC25-IN-1
  • HY-173228
    Anticancer agent 269
    		Activator
    Anticancer agent 269 (Compound 11c) is an orally active caspase-3 activator that promotes ROS generation by activating caspase-3, induces cancer cell apoptosis (Apoptosis), and exhibits significant anticancer activity. It can be used for research in the field of cancer.
    Anticancer agent 269
  • HY-P10285S
    d-KLA Peptide-d30
    d-KLA Peptide-d30 (D-(KLAKLAK)2-d30) is the deuterium labeled d-KLA Peptide (HY-P10285). d-KLA Peptide is a synthetic pro-apoptotic peptide. d-KLA Peptide can specifically target mitochondria and induce apoptosis by destroying the mitochondrial membrane. d-KLA Peptide activates biochemical pathways associated with apoptosis, including the activation of caspase family proteins and PARP (poly ADP ribose polymerase). d-KLA Peptide can be used to carry and deliver genes or small molecules to enhance anti-tumor effects.
    d-KLA Peptide-d<sub>30</sub>
  • HY-P5890A
    YVAD-CHO TFA
    		Inhibitor
    YVAD-CHO TFA is an interleukin-1β converting enzyme (ICE, caspase 1) inhibitor (Ki: 0.76 nM). YVAD-CHO TFA inhibits mature IL-1β production. YVAD-CHO TFA partially delays motoneurone death in lesioned facial nerve mice.
    YVAD-CHO TFA
  • HY-P10162
    Ac-DMQD-AMC
    Ac-DMQD-AMC is an inhibitor of caspase-3. Ac-DMQD-AMC is an aromatic amine using aminium-based coupling reagent HATU in the presence of 2,4,6-trimethylpyridine (TMP).
    Ac-DMQD-AMC
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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