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-116572
    TASIN-1 hydrochloride
    		Activator
    TASIN-1 hydrochloride is a selective inhibitor of truncated APCTR (adenomatous polyposis coli gene) that exerts cytotoxic effects by inhibiting cholesterol biosynthesis. TASIN-1 hydrochloride specifically targets colorectal cancer (CRC) cells carrying APC truncated mutations, while having no significant toxicity to wild-type APC cells. TASIN-1 hydrochloride exerts cytotoxic effects by targeting Emopamil binding protein (EBP) to inhibit cholesterol biosynthesis, triggering endoplasmic reticulum (ER) stress, reactive oxygen species (ROS) generation, and JNK-mediated apoptosis, and inhibiting Akt survival signaling. TASIN-1 hydrochloride can be used to prevent and intervene in APC mutant colorectal cancer.
    TASIN-1 hydrochloride
  • HY-119459R
    Fluopyram (Standard)
    		Activator
    Fluopyram (Standard) is the analytical standard of Fluopyram (HY-119459). This product is intended for research and analytical applications. Fluopyram is an orally active succinate dehydrogenase inhibitor, antifungal and nematicide. Fluopyram inhibits succinate dehydrogenase activity, activates CAR/PXR nuclear receptors, and increases caspase-3, TNF-α and NF-κB. Fluopyram inhibits the growth of F. virguliforme, Botrytis cinerea and Alternaria solani with EC50 values of 3.35, 5.389 and 0.244 µg/mL, respectively. Fluopyram induces liver and thyroid tumor formation. Fluopyram is nephrotoxic and embryotoxic.
    Fluopyram (Standard)
  • HY-B0464R
    Hydralazine (hydrochloride) (Standard)
    Hydralazine (hydrochloride) (Standard) is the analytical standard of Hydralazine (hydrochloride). This product is intended for research and analytical applications. Hydralazine hydrochloride is an antihypertensive agent. Hydralazine hydrochloride can inhibit mitochondrial fission and human peritoneal mesothelial cell proliferation. Hydralazine hydrochloride has immunomodulation and anti-migratory effect. Hydralazine hydrochloride activates the intrinsic pathway of apoptosis and causes DNA damage.
    Hydralazine (hydrochloride) (Standard)
  • HY-119807
    Prosultiamine
    Prosultiamine is an allithiamine homolog. Prosultiamine can disrupt intracellular redox reactions, inducing caspase-dependent apoptosis in HTLV-1 infected cells. Prosultiamine can be used in studies involving lower urinary tract dysfunction associated with human T-lymphotropic virus type 1-related myelopathy/tropical spastic paraparesis.
    Prosultiamine
  • HY-B1971S1
    Deltamethrin-d6
    Deltamethrin-d6 (Decamethrin-d6) is deuterium labeled Deltamethrin. Deltamethrin (Decamethrin) is an orally active synthetic pyrethroid insecticide. Deltamethrin induces oxidative stress and results in inflammation and apoptosis via inhibiting Nrf2/HO-1 pathway. Deltamethrin has an anticancer effect by inducing apoptosis. Deltamethrin can be used extensively in pest control.
    Deltamethrin-d<sub>6</sub>
  • HY-N15378
    β-Carotene-15,15'-epoxide
    		Inhibitor
    β-carotene-15,15ʹ-epoxide is a XIAP antagonist with apoptosis-inducing and antitumor activity, found in the leaves of Spondias mombin. In a DMBA (HY-W011845)-induced rat model of breast cancer, β-carotene-15,15ʹ-epoxide binds to the BIR3 domain of the anti-apoptotic protein XIAP, blocking its interaction with caspase-9 and thereby promoting tumor cell apoptosis. In addition, β-carotene-15,15ʹ-epoxide significantly downregulates the expression of BCL-2, COX-2, and TNF-α in tumor tissues, reduces MDA levels, increases catalase activity, and modulates serum levels of LDH, ALP, and ALT, demonstrating strong antioxidant, anti-inflammatory, and metabolic protective effects. β-carotene-15,15ʹ-epoxide may be used in research on inflammation-related conditions and cancers such as breast cancer.
    β-Carotene-15,15'-epoxide
  • HY-N6979R
    Crustecdysone (Standard)
    		Inhibitor
    Crustecdysone (Standard) is the analytical standard of Crustecdysone. This product is intended for research and analytical applications. Crustecdysone (20-Hydroxyecdysone) is a naturally occurring ecdysteroid hormone isolated from Serratula coronata which controls the ecdysis (moulting) and metamorphosis of arthropods, it inhibits caspase activity and induces autophagy via the 20E nuclear receptor complex, EcR-USP. Crustecdysone exhibits regulatory or protective roles in the cardiovascular system. Crustecdysone is an active metabolite of Ecdysone (HY-N0179).
    Crustecdysone (Standard)
  • HY-P6285
    Z-TPE-2DEVD
    Z-TPE-2DEVD is a specific probe for caspase-3.
    Z-TPE-2DEVD
  • HY-N8508
    Myrothecine A
    		Activator
    Myrothecine A is a trichothecene mycotoxin found in M. roridum. Myrothecine A induces apoptosis, promotes the cytochrome c release, PARP-cleavage and phosphorylation of JNK, increases Bax and cleaved caspase-3, -5, and -8 levels. Myrothecine A has anticancer activities and promotes the maturation of DC cells in the microenvironment. Myrothecine A inhibits proliferation of A549, MCF-7, HepG2, and SMMC-7721 cancer cells with IC50s of 95, 70, 60, and 25 µM, respectively.
    Myrothecine A
  • HY-165537
    Siphonaxanthin
    		Activator
    Siphonaxanthin is a keto-carotenoid with anti-angiogenic and anti-inflammatory activity, which is found in green algae. Siphonaxanthin upregulates the expression of death receptor 5 (DR5), induces cancer cell apoptosis, decreases the expression of Bcl-2, and activates caspase-3. Siphonaxanthin is also an inhibitor of FGFR-1. Siphonaxanthin inhibits the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs), as well as the outgrowth of microvessels in the rat aortic ring. Siphonaxanthin is promising for research of diseases such as cancer, diabetic retinopathy, and rheumatoid arthritis.
    Siphonaxanthin
  • HY-134563
    Z-Asp(OMe)-Gln-Met-Asp(OMe)-FMK
    		Inhibitor
    Z-Asp(OMe)-Gln-Met-Asp(OMe)-FMK is an inhibitor for caspase-3, and inhibits Dihydroartemisinin (HY-N0176) and Dictamnine (HY-N0849) co-induced apoptosis.
    Z-Asp(OMe)-Gln-Met-Asp(OMe)-FMK
  • HY-N2014R
    Verbenalin (Standard)
    		Inhibitor
    Verbenalin (Standard) is the analytical standard of Verbenalin. This product is intended for research and analytical applications. Verbenalin is an orally active terpenoid glycoside that can be extracted from the medicinal plant Verbena officinalis. Verbenalin has anti-inflammatory, antiviral, and neuroprotective effects. Verbenalin has a strong binding affinity to the nsp-12 protein of the SARS-CoV-2 virus. Verbenalin can be used in the research of inflammatory and nervous system diseases such as hepatitis and Alzheimer's disease.
    Verbenalin (Standard)
  • HY-W338079
    Ac-Asp-Glu-Val-Asp-pNA
    		Substrate
    Ac-Asp-Glu-Val-Asp-pNA is a peptidic substrate of caspase-3/7.
    Ac-Asp-Glu-Val-Asp-pNA
  • HY-124134
    AD-2646
    		Activator
    AD-2646 (LCL102), a ceramide analog, can kill leukemic T cells (EC50: 40 μM). AD-2646 triggers the cleavage of caspase-8, -9 and -3, as well as the caspase substrate PARP. AD-2646 is a ceramidase inhibitor. AD-2646 induces an accumulation of endogenous ceramide owing to perturbed ceramide metabolism.
    AD-2646
  • HY-126365
    Alisol B acetate
    		Activator
    Alisol B acetate is a Triterpenoids product that can be isolated from the tubers of Alisma plantago-aquatica Linn..
    Alisol B acetate
  • HY-B1193R
    Terfenadine (Standard)
    		Activator
    Terfenadine (Standard) is the analytical standard of Terfenadine. This product is intended for research and analytical applications. Terfenadine ((±)-Terfenadine) is a potent open-channel blocker of hERG with an IC50 of 204 nM. Terfenadine, an H1 histamine receptor antagonist, acts as a potent apoptosis inducer in melanoma cells through modulation of Ca2+ homeostasis. Terfenadine induces ROS-dependent apoptosis, simultaneously activates Caspase-4, -2, -9.
    Terfenadine (Standard)
  • HY-B1135R
    Benzbromarone (Standard)
    Benzbromarone (Standard) is the analytical standard of Benzbromarone. This product is intended for research and analytical applications. Benzbromarone is an orally active anti-gout agent. Benzbromarone has anti-infammatory, anti-oxidative stress and nephroprotective effects. Benzbromarone can be used for the research of hyperuricemia and gout.
    Benzbromarone (Standard)
  • HY-117136
    AN-7
    		Activator
    AN-7 is an orally active histone deacetylase (HDAC) inhibitor that induces histone hyperacetylation and differentiation in vitro and in vivo, and inhibits the proliferation of human prostate 22Rv1 cancer cells. AN-7 can increase the expression of the pro-apoptotic protein Bax, reduce the expression of the anti-apoptotic protein Bcl-2, and promote apoptosis by activating caspase-3, and can be used in the study of prostate cancer.
    AN-7
  • HY-N7000R
    Perillyl alcohol (Standard)
    		Activator
    Perillyl alcohol (Standard) is the analytical standard of Perillyl alcohol (HY-N7000). Perillyl alcohol is an orally active monoterpene. Perillyl alcohol exhibits multiple activities such as analgesic, anti-inflammatory, anti-tumor, anti-angiogenic, and anti-nociceptive effects. Perillyl alcohol can induce apoptosis and cell cycle arrest in tumor cells.
    Perillyl alcohol (Standard)
  • HY-P10666
    Ac-VDQQD-pNA
    Ac-VDQQD-pNA is a substrate of Caspase 2 and can be cleaved to produce yellow pNA (p-nitroaniline).
    Ac-VDQQD-pNA
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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