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-118304
    AKN-028
    		Activator
    AKN-028, 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 inhibits FLT3 autophosphorylation. AKN-028 induces dose-dependent cytotoxic response (mean IC50=1 μM). AKN-028 induces apoptosisby activation of caspase 3. AKN-028 can be used in research of acute myeloid leukemia (AML).
    AKN-028
  • HY-P5122
    Z-LEED-FMK
    		Inhibitor
    Z-LEED-FMK is a caspase-13 and caspase-4 inhibitor. Z-LEED-FMK also inhibits caspase-1 processing in S. typhimurium-infected macrophages.
    Z-LEED-FMK
  • HY-B0347S3
    Lacidipine-13C4
    		Modulator
    Lacidipine-13C4 is 13C labeled Lacidipine (HY-B0347). Lacidipine is an orally active and highly selective L-type calcium channel blocker that acts on smooth muscle calcium channels, primarily dilates peripheral arteries, reduces peripheral resistance, and has long-lasting anti-hypertensive activity. Lacidipine protects HKCs from apoptosis induced by ATP depletion and recovery by modulating the caspase-3 pathway. Lacidipine can be used in studies of hypertension, atherosclerosis and acute kidney injury (AKI).
    Lacidipine-<sup>13</sup>C<sub>4</sub>
  • HY-N6681
    15-Acetoxyscirpenol
    		Activator 99.35%
    15-acetoxyscirpenol, one of acetoxyscirpenol moiety mycotoxins (ASMs), strongly induces apoptosis and inhibits Jurkat T cell growth in a dose-dependent manner by activating other caspases independent of caspase-3.
    15-Acetoxyscirpenol
  • HY-W040329S3
    2'-Deoxyadenosine-15N5,d13
    		Activator
    2'-Deoxyadenosine-15N5,d13 is deuterium and 15N labeled 2'-Deoxyadenosine (HY-W040329). 2′-Deoxyadenosine is an adenine nucleoside that inhibits glucose-stimulated insulin release. 2′-Deoxyadenosine inhibits glucose-stimulated increases seen in islet cyclic AMP (cAMP) accumulation. 2'-Deoxyadenosine activates caspase-3 and promotes apoptosis. 2'-Deoxyadenosine inhibits the activity of S-adenosyl-L-homocysteine hydrolase (SAHH). 2'-Deoxyadenosine inhibits the growth of various cells. 2'-Deoxyadenosine has an anticancer effect on colon cancer.
    2'-Deoxyadenosine-<sup>15</sup>N<sub>5</sub>,d<sub>13</sub>
  • HY-RS01969
    CASP9 Human Pre-designed siRNA Set A
    		Inhibitor

    CASP9 Human Pre-designed siRNA Set A contains three designed siRNAs for CASP9 gene (Human), as well as a negative control, a positive control, and a FAM-labeled negative control.
    CASP9 Human Pre-designed siRNA Set A
  • HY-P5834
    Boc-AEVD-CHO
    		Inhibitor 98.34%
    Boc-AEVD-CHO is a Caspase 8 inhibitor useful in the study of apoptosis and immune and inflammatory diseases.
    Boc-AEVD-CHO
  • HY-P5974
    Z-YVAD-pNA
    Z-YVAD-pNA (Z-Tyr-Val-Ala-Asp-pNA) is a caspase-1 substrate.
    Z-YVAD-pNA
  • HY-13559A
    Atiprimod dimaleate
    		Activator
    Atiprimod (Azaspirane) (dimaleate) is a STAT3 inhibitor with antitumor, anti-inflammatory, and anti-angiogenic activities. Atiprimod blocks the signaling pathways of IL-6 and VEGF by inhibiting the phosphorylation of signal transducer and activator of STAT3. Atiprimod blocks the JAK-STAT signaling pathway by inhibiting the phosphorylation of JAK2 and JAK3. Atiprimod also inhibits cell proliferation, induces cell cycle arrest, and induces autophagy and apoptosis. Atiprimod triggers persistent ER stress-mediated apoptosis in breast cancer cells by activating the PERK/eIF2α/ATF4/CHOP axis and inhibiting the nuclear translocation of STAT3/NF-κB. Atiprimod shows great anti-tumor activities in tumor xenograft mouse models. Atiprimod can be used for the study of pituitary adenoma, breast cancer, multiple myeloma and acute myeloid leukemia (AML).
    Atiprimod dimaleate
  • HY-N11648
    Ganoderic acid T1
    		Activator
    Ganoderic acid T1 is a deacetylated derivative of Ganoderic acid T. Ganoderic acid T1 attenuates antioxidant defense system and induces apoptosis of cancer cells. Ganoderic acid T1 decreases mitochondrial membrane potential and activates caspase-9 and caspase-3, to trigger apoptosis. Ganoderic acid T1 also increases the generation of intracellular ROS to produce pro-oxidant activities and cytotoxicity.
    Ganoderic acid T1
  • HY-174260
    Neuroprotective agent 11
    Neuroprotective agent 11 (Compound 1a) is an orally active polyphenol compound with significant protective effects against cerebral ischemia. The main activities of Neuroprotective agent 11 include inhibiting neuronal inflammation and apoptosis, reducing cerebral infarction volume, and improving behavioral symptoms of cerebral ischemic mice. Neuroprotective agent 11 exerts its regulatory mechanism by downregulating the expression of inflammatory factors (iNOS、COX-2) and apoptotic proteins (cleaved-Caspase3, p53). Neuroprotective agent 11 can be used in the study of cerebral ischemia-related diseases (such as ischemic stroke).
    Neuroprotective agent 11
  • HY-117249
    Sanazole
    		Agonist
    Sanazole (AK-2123) is a hypoxic cell radiosensitizer. Sanazole enhances radiation-induced DNA strand breaks. In mouse fibroblast tumors, Sanazole increases nuclear condensation and fragmentation, as well as elevates caspase-3 activity, thereby enhancing radiation-induced apoptosis. These characteristics make Sanazole a promising candidate for research in tumor therapy.
    Sanazole
  • HY-P10084
    Ac-VAD-pNA
    Ac-VAD-pNA is a caspase-1 substrate. Ac-VAD-pNA can be used to detect caspase-1 activity.
    Ac-VAD-pNA
  • HY-175236
    SF-9-2
    		Agonist
    SF-9-2 is a PD-L1/PD-1 binding inhibitor (IC50 = 24.9 nM). SF-9-2 inhibits epithelial-mesenchymal transition, migration, invasion, and proliferation of SK-N-SH cells, and also induces apoptosis and cell cycle arrest. SF-9-2 blocks PD-L1-induced SK-N-SH cell growth through the MAPK signaling pathway. SF-9-2 restores GSK-3β activity and enhances PD-L1 degradation through the ubiquitin-proteasome pathway. SF-9-2 inhibits tumor growth in the SK-N-SH NOG mouse model without significant toxicity. SF-9-2 also acts as an immune checkpoint inhibitor, blocking PD-L1 to restore T cell function. SF-9-2 can be used in neuroblastoma research.
    SF-9-2
  • HY-W040329S
    2'-Deoxyadenosine-13C10,15N5
    		Activator
    2'-Deoxyadenosine-13C10,15N5 is 13C and 15N-labeled 2'-Deoxyadenosine (HY-W040329). 2′-Deoxyadenosine is an adenine nucleoside that inhibits glucose-stimulated insulin release. 2′-Deoxyadenosine inhibits glucose-stimulated increases seen in islet cyclic AMP (cAMP) accumulation. 2'-Deoxyadenosine activates caspase-3 and promotes apoptosis. 2'-Deoxyadenosine inhibits the activity of S-adenosyl-L-homocysteine hydrolase (SAHH). 2'-Deoxyadenosine inhibits the growth of various cells. 2'-Deoxyadenosine has an anticancer effect on colon cancer.
    2'-Deoxyadenosine-<sup>13</sup>C<sub>10</sub>,<sup>15</sup>N<sub>5</sub>
  • HY-179023
    CDK9-IN-45
    		Activator
    CDK9-IN-45 (Compound B11) is a highly selective CDK9 inhibitor with IC50 values for CDK9 and CDK1 of 7.13 and 489.5 nM respectively. CDK9-IN-45 exhibits a potent inhibitory effect on colorectal cancer cells. CDK9-IN-45 induces cell apoptosis and leads to significant accumulation of ROS. CDK9-IN-45 activates Caspase-3, downregulates Mcl-1, XIAP, and c-Myc. CDK9-IN-45 can be used for research on colorectal cancer.
    CDK9-IN-45
  • HY-155570
    Anticancer agent 137
    		Inducer
    Anticancer agent 137 (8q) is a potent PI3k inhibitor. Anticancer agent 137 has broad-spectrum anticancer activity. Anticancer agent 137 induces G2/M cell cycle arrest and apoptosis. Anticancer agent 137 increases cleaved PARP, caspase 3, and 7. Anticancer agent 137 can be used in research of cancer.
    Anticancer agent 137
  • HY-178941
    DHODH-IN-32
    		Activator
    DHODH-IN-32 (Compound A1) is a DHODH inhibitor. DHODH-IN-32 shows significant cytotoxicity against NCI-60 cell lines, especially being sensitive to breast cancer, prostate cancer and leukemia cell lines. DHODH-IN-32 can induce cell apoptosis by activating the Caspase pathway. DHODH-IN-32 causes G0/G1 phase cell cycle arrest and inhibits cellular metabolism by ROS. DHODH-IN-32 exhibits significant anti-tumor properties in mouse breast cancer models. DHODH-IN-32 can be used for the study of breast cancer.
    DHODH-IN-32
  • HY-P2614
    Mca-DEVDAP-K(Dnp)-OH
    		Chemical
    Mca-DEVDAP-K(Dnp)-OH is a fluorogenic substrate for caspase-3.
    Mca-DEVDAP-K(Dnp)-OH
  • HY-N2071R
    Cedrol (Standard)
    		Activator
    Cedrol (Standard) is the analytical standard of Cedrol. This product is intended for research and analytical applications. Cedrol is a potent competitive inhibitor of cytochrome P-450(CYP) enzyme. Cedrol plays an anticancer role by inducing cell cycle arrest and Caspase-dependent apoptosis. Cedrol acts as a neutrophil agonist that can desensitize cells to subsequent stimulation of N-formyl peptides. Cedrol prevents neuropathic pain caused by chronic contractile injury by inhibiting oxidative stress and inflammation. In addition, Cedrol has antibacterial, hair loss prevention and anti-anxiety properties.
    Cedrol (Standard)
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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