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-B0347
    Lacidipine
    		Modulator 99.79%
    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
  • HY-17583
    Griseofulvin
    		99.05%
    Griseofulvin is an orally active antifungal antibiotic with antitumor activity. Griseofulvin induces apoptosis and G2/M cell cycle arrest in cancer cells. Griseofulvin also has cardiovascular modulatory activity, reducing angina pectoris, relieving hand artery spasm associated with onychomycosis, and peripheral vascular diseases such as shoulder-hand syndrome.
    Griseofulvin
  • HY-101448
    TMI-1
    		Activator 99.59%
    TMI-1 (WAY-171318) inhibits TNF converting enzyme (TACE) (IC50 of 8.4 nM), ADAM-TS-4, ADAM-17 and various MMPs with oral activity. TMI-1 significantly suppresses the secretion of TNF-α , alleviating collagen-induced arthritis in mice. TMI-1 inhibits cancer cell proliferation, induces apoptosis through a caspase-dependent pathway. TMI-1 also reverses TRPV1 upregulation and lowers the levels of inflammatory factors (TNF-α、IL-1β、IL-6) in nerve cells, protecting against paclitaxel-induced neurotoxicity. TMI-1 leads to changes in pro-atherogenic lipoprotein profiles, but does not affect the progression of early lesions.
    TMI-1
  • HY-120019
    Ac-YVAD-CHO
    		Inhibitor 98.23%
    Ac-YVAD-CHO (L-709049) is a potent, reversible, specific tetrapeptide interleukin-lβ converting enzyme (ICE) inhibitor with mouse and human Ki values of 3.0 and 0.76 nM. Ac-YVAD-CHO is also a caspase-1 inhibitor. Ac-YVAD-CHO can suppress the production of mature IL-lβ.
    Ac-YVAD-CHO
  • HY-19204
    Zinc phthalocyanine
    		Activator ≥98.0%
    Zinc phthalocyanine (ZnPc) is commonly applied in industry (catalysts, photoconductors) and biomedical (photodynamic therapy, PDT). Zinc phthalocyanine can be used to photooxidise cyclohexane and is promising for research of solar-cell applications.
    Zinc phthalocyanine
  • HY-112137
    Trehalose-6,6'-dibehenate
    		≥98.0%
    Trehalose-6,6'-dibehenate is an orally active glycolipid. Trehalose-6,6'-dibehenate activates Mincle and inflammasome, inducing IL-1β secretion in a caspase activity-dependent manner. Trehalose-6,6'-dibehenate exerts a Myd88-dependent adjuvant activity. Trehalose-6,6'-dibehenate induces Th-1/Th-17 immune responses.
    Trehalose-6,6'-dibehenate
  • HY-10397A
    MX1013
    		Inhibitor ≥99.0%
    MX1013 is a potent, irreversible dipeptide caspase inhibitor vith antiapoptotic activity. MX1013 inhibits recombinant human caspase 3 with an IC50 of 30 nM.
    MX1013
  • HY-W042191
    Oxychlororaphine
    		Activator 98.90%
    Oxychloroaphine could be isolated from the bacterium Pantoea agglomerans naturally present in soil. Oxychloroaphine has broad-spectrum antifungal activity. Oxychloroaphine has cytotoxicity in a dose-dependent manner and induces apoptosis. Oxychloroaphine can be used in research of cancer.
    Oxychlororaphine
  • HY-N0840
    Bruceantin
    		Activator 99.94%
    Bruceantin ((-)-Bruceantin) is a quassinoid found in B. javanica. Bruceantin activates caspase signaling pathway, causes the mitochondrial dysfunction, inhibits cell proliferation, induces cell differentiation and apoptosis. Bruceantin exhibits anti-leukemia and antiprotozoal activities.
    Bruceantin
  • HY-N0726
    Dracorhodin perchlorate
    		Activator 99.14%
    Dracorhodin perchlorate (Dracohodin perochlorate) is a natural product. Dracorhodin perchlorate can be obtained from the natural active molecule Dragon's blood. Dracorhodin perchlorate inhibits PI3K/Akt and NF-κB activation, upregulates p53 expression, activates caspase, produces ROS, and promotes Apoptosis. Dracorhodin perchlorate regulates the TLR4. Dracorhodin perchlorate promotes wound healing, improves diabetes. Dracorhodin perchlorate has anti-tumor activity against prostate cancer, breast cancer, cervical cancer and other cancers.
    Dracorhodin perchlorate
  • HY-164388
    Z-VAD
    		Inhibitor 99.53%
    Z-VAD is a competitive, irreversible pan-caspase inhibitor. Z-VAD inhibits all 10 caspases, except for caspase-2 which is only weakly inhibited. Z-VAD decreases radiation-induced apoptosis. Z-VAD induces both autophagy and necrosis in irradiated MDA-MB-231 and H460 mouse xenografts. Z-VAD with radiation produces a significant tumor growth delay and shows dramatic antiangiogenic effect in cancer xenograft.
    Z-VAD
  • HY-N7015
    Zerumbone
    		99.87%
    Zerumbone is an orally active natural cyclic sesquiterpene and can be isolated from Zingiber zerumbet. Zerumbone has anti-proliferative, anti-inflammation, anti-cancer, anti-bacterial and anti-mutagenic activity.
    Zerumbone
  • HY-N0674B
    Dehydrocorydaline (hydroxyl)
    		Activator 99.52%
    Dehydrocorydaline (13-Methylpalmatine) hydroxyl is an alkaloid that regulates protein expression of Bax, Bcl-2; activates caspase-7, caspase-8, and inactivates PARP. Dehydrocorydaline hydroxyl elevates p38 MAPK activation. Anti-inflammatory and anti-cancer activities. Dehydrocorydaline hydroxyl shows strong anti-malarial effects (IC50=38 nM), and low cytotoxicity (cell viability > 90%) using P. falciparum 3D7 strain.
    Dehydrocorydaline (hydroxyl)
  • HY-B0263
    Thiabendazole
    		99.77%
    Thiabendazole is an orally available benzimidazole fungicide with repellent and anticancer activities. Thiabendazole can result in developmental malformations. Thiabendazole can be used for modeling.
    Thiabendazole
  • HY-Y0148
    10-Hydroxydecanoic acid
    		Inhibitor 98.77%
    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.
    10-Hydroxydecanoic acid
  • HY-18676B
    ILK-IN-2
    		Inhibitor 99.41%
    ILK-IN-2 (OSU-T315 analog) is an oral PDK2 inhibitor and also an ILK inhibitor, with an IC50 of 0.6 μM. ILK-IN-2 induces cell autophagy and apoptosis, showing anti-tumor activity. ILK-IN-2 directly abolishes AKT activation by preventing AKT from translocating to lipid rafts, triggering Caspase-dependent apoptosis in chronic lymphocytic leukemia (CLL) and extending the lifespan in TCL1 mouse models.
    ILK-IN-2
  • HY-148258
    GDC-2394
    		Inhibitor 99.54%
    GDC-2394 is an orally active and selective NLRP3 inhibitor, and also inhibits IL-1β with IC50s of 0.4 μM (human IL-1β) and 0.1 μM (mouse IL-1β). GDC-2394 inhibits NLRP3-induced caspase-1 activity without inhibiting NLRC4-dependent inflammasome activation.
    GDC-2394
  • HY-B1839
    Fluazinam
    		Activator 99.36%
    Fluazinam is an orally active dinitroaniline fungicide. Fluazinam induces phosphorylation of JNK, activates p38 pathway, decreases Bcl-2, activates caspase-3, decreases complex I activity, increases Autophagy and Apoptosis. Fluazinam has strong antifungal activity against F. fujikuroi and B. maydis. Fluazinam has a negative impact on Brachydanio rerio and worker bees.
    Fluazinam
  • HY-19696B
    Tauroursodeoxycholate dihydrate
    		Inhibitor 99.86%
    Tauroursodeoxycholate (Tauroursodeoxycholic acid; TDUCA) dihydrate is an endoplasmic reticulum (ER) stress inhibitor. Tauroursodeoxycholate significantly reduces expression of apoptosis molecules, such as caspase-3 and caspase-12. Tauroursodeoxycholate also inhibits ERK.
    Tauroursodeoxycholate dihydrate
  • HY-P1169
    Ac-IETD-AFC
    		99.91%
    Ac-IETD-AFC is a fluorogenic substrate of caspase-8, caspase-3, caspase-10, and granzyme B.
    Ac-IETD-AFC
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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