caspase 3

Z-DEVD-FMK, a Caspase-3 Inhibitor, is an irreversible, cell-permeable inhibitor of caspase-3/CPP32 that impedes tumor cell apoptosis. In vivo studies show it offers neuroprotection in rat hippocampi post-seizures and considerably diminishes post-traumatic apoptosis, enhancing neurological recovery in rats before and after traumatic brain injury induction.

Caspase-3 activator 1 (compound 4b), a Ru(III) metal complex, effectively inhibits gastric tumor growth and metastasis by mediating caspase-3 cleavage, enabling Caspase-3 to process gasdermin E (GSDME), resulting in GSDME-N terminus production and perforation of the gastric tumor cell membrane. Furthermore, compound 4b induces pyroptosis and subsequent immune responses and can be incorporated with decitabine (DCT) into the 4b-DCT-Lip lipid delivery system [1].

Caspase-3-IN-1 is a potent inhibitor of Caspase-3 (IC50: 14.5 nM).

Caspase-3 activator 3 (compound 2h) effectively induces apoptosis in HL-60 and K562 cells by substantially activating caspase-3, demonstrating antileukemic activity with IC50 values of 42.89 μM and 33.61 μM, respectively [1].

Caspase-3 Activator 2 (Compound 2f) is a caspase 3 activator with cytotoxic effects on HL-60 and K562 cells, exhibiting IC 50 values of 33.52 μM and 76.90 μM, respectively [1]. It facilitates apoptosis, rendering it useful in cancer research.

Caspase-3/7 Activator 2 is a potent compound that selectively activates Caspase-3/7, demonstrating tumor specificity, anti-proliferative properties, and a high capacity for inducing apoptosis.

Caspase-3/7 Activator 3 is a potent and tumor-selective compound that effectively activates Caspase-3/7, demonstrating significant anti-proliferative activity and a high capacity to induce apoptosis.

Caspase-3 Inhibitor I (N-acetyl-asp-glu-val-asp-al) is a specific inhibitor of Caspase-3.

Z-DEVD-FMK (Caspase-3 Inhibitor) is a selective, irreversible Caspase-3 inhibitor, and also exhibits effective inhibition activity on caspase-6, caspase-7, caspase-8, and caspase-10.

MMPSI (Caspase-3/7 Inhibitor I) is a novel, non-peptide small molecule caspase 3 and caspase 7 inhibitor that reduces ischemic injury in isolated rabbit heart or cardiomyocytes and inhibits apoptosis of H16c2 cells in a concentration-dependent manner.MMPSI can be used to study cardioprotection and myocardial injury.

Ivachtin (Caspase-3 Inhibitor VII) is a nonpeptide, noncompetitive and reversibl caspase-3 inhibitor(IC50 = 23 nM) and is a modest inhibitor of the remaining caspases.

Procyanidin C1 is a natural product, with anti-inflammatory effects, and induces apoptosis.

2-methoxycinnamaldehyde is a natural compound of Cinnamomum cassia,has been widely studied with regard to its antitumor activity.

Taurochenodeoxycholic Acid (12-Deoxycholyltaurine) is one of the main bioactive substances of animals' bile acid.

Tauroursodeoxycholate sodium (TUDC) is an endoplasmic reticulum (ER) stress inhibitor, used for the treatment of gallstones and liver cirrhosis.

Amygdalin (Laetrile) has antifibrotic, antitumor, anti-inflammatory and analgesic effects, amygdalin joint HSYA could inhibit the degeneration of the endplate chondrocytes derived from intervertebral discs of rats induced by IL-1beta and better than the single use of Amygdalin or HSYA. Amygdalin induces apoptotic cell death in human DU145 and LNCaP prostate cancer cells by caspase-3 activation through down-regulation of Bcl-2 and up-regulation of Bax.

Citronellol ((±)-β-Citronellol) is used in insect repellents and perfumes and as a mite attractant.

Pargyline hydrochloride (Pargylamine hydrochloride) is an irreversible monoamine oxidase(MAO) inhibitor with antihypertensive properties.

Metronidazole (Metronidazol) is a synthetic nitroimidazole derivative with antiprotozoal and antibacterial activities.

Isoflurane (Forane) is a stable, non-explosive inhalation anesthetic that has been reported to induce caspase-3 activation.

Tauroursodeoxycholate (UR 906), also known as ursodoxicoltaurine, is a highly hydrophilic tertiary bile acid that is produced in humans at a low concentration. Tauroursodeoxycholate is the more hydrophilic form of ursodeoxycholic acid, which is the more abundant naturally produced bile acid in humans.Tauroursodeoxycholate is being investigated for use in several conditions such as Primary Biliary Cirrhosis (PBC), insulin resistance, amyloidosis, Cystic Fibrosis, Cholestasis, and Amyotrophic Lateral Sclerosis.

Emamectin Benzoate (MK-244), by binding gamma-aminobutyric acid (GABA) receptor and glutamate-gated chloride channels disrupting nerve signals within arthropods, acts as a chloride channel activator.

Pargyline (Pargylamine) is a monoamine oxidase inhibitor with antihypertensive properties.

Taurochenodeoxycholic acid sodium (Sodium taurochenodeoxycholate) is one of the main bioactive substances of animals' bile acid. Taurochenodeoxycholic acid sodium induces apoptosis and shows obvious anti-inflammatory and immune regulation properties. It can increase glucose-induced insulin secretion and stimulate the electrical activity of α2-cells and enhance cytosolic Ca(2+) concentration ([Ca(2+)](c)).

VU0285655-1(BML-280) is a potent and selective phospholipase D2 (PLD2) inhibitor that inhibits the proliferation of PLD2-deficient cells.VU0285655-1 has an inhibitory effect on high glucose-induced caspase-3 cleavage and reduction of cell viability.VU0285655-1 is used in the study of diabetic retinopathy.

SKLB-163 acts by downregulating RhoGDI, activating JNK-1 signaling pathway and caspase-3, and reducing phosphorylated Akt and p44/42 MAPK.

Arg-Gly-Asp-Ser acetate is an integrin binding sequence that directly and specifically bind pro-caspase-8, pro-caspase-9 and pro-caspase-3, while it does not bind pro-caspase-1. Arg-Gly-Asp-Ser acetate inhibits integrin receptor function.

ALPHA-PINENE ((-)-Alpha-Pinene) is a bicyclic monoterpene found in pine trees and other plants, including Cannabis with diverse biological activities [1]. It reduces the growth of a panel of seven Gram-positive bacteria, seven Gram-negative bacteria, and eight yeast strains with MIC values of 0.75-1.29, 1.05-1.59, and 0.7-1.17%, respectively [2]. It has insecticidal activity against C. molestus larvae with LC50 values ranging from 47 to 49 mg/L.3 ALPHA-PINENE (100 μg/ml) induces apoptosis, increases anion superoxide production and DNA fragmentation, and activates caspase-3 in B16/F10 melanoma cells [4]. In a B16/F10 mouse xenograft model, ALPHA-PINENE(100 ml of a 10 mg/ml solution) reduces the number of metastatic lung nodules by approximately 7-fold. ALPHA-PINENE(8.6 mg/L, aerosol) also increases the time spent in the open arms of the elevated plus maze by approximately 2-fold in mice, indicating anxiolytic-like activity [5].

EF24 (3,5-Bis[(2-fluorophenyl)Methylene]-4-piperidinone) treatment increases the levels of activated caspase 3 and 9, and decreases the phosphorylated forms of MEK1 and ERK. EF24 shows potent anti-tumor activity in oral squamous cell carcinoma (OSCC) via deactivation of the MAPK/ERK signaling pathway.

CSRM617 hydrochloride is a selective small-molecule inhibitor of the transcription factor ONECUT2 (OC2, a master regulator of androgen receptor), with a Kd of 7.43 µM in SPR assays, directly binding to the OC2-HOX domain. CSRM617 hydrochloride induces apoptosis through the appearance of cleaved Caspase-3 and PARP and is well tolerated in the mouse model of prostate cancer [1].

OUP-186 is a high affinity and human/rat species-selective antagonist of histamine H3 receptor. OUP-186 suppressed the proliferation of breast cancer cells. The IC50 values at 48 hours for OUP-186 was approximately 50 μM. OUP-186 potently induced cell dea

AKN-028 is an orally active and potent FLT3 tyrosine kinase inhibitor ( IC 50 = 6 nM). AKN-028 causes dose-dependent inhibition of FLT3 autophosphorylation.

Cysteine protease inhibitor 2 is a cysteine protease inhibitor. Cysteine protease inhibitor 2 inhibited DCT116 and PC3 cells with GI50 values of 6.5 μM and 4.4 μM, respectively.

1. Chelidonine (Stylophorin) isolated from Chelidonium majus efficiently induced apoptosis in HeLa cells through possible alteration of p38-p53 and AKT/PI3 kinase signalling pathways. 2. Chelidonine is a promising model compound for overcoming MDR and for enhancing cytotoxicity of chemotherapeutics, especially against leukaemia cells, its efficacy needs to be confirmed in animal models. 3. Chelidonine may be a potential therapeutic agent against metastasis of invasive human cancer cells, exhibits antimigratory and antiinvasive effects in MDA-MB-231 cells, by suppressing COL-induced integrin signaling, through inhibiting the formation of the IPP complex and subsequent downregulation of IPP downstream signaling molecules, such as Akt and ERK1/2.

Fraxetin (7,8-dihydroxy-6-methoxy coumarin) has dual-antioxidative ,hepatoprotective and antihyperglycemic functions, it shows potent protective effects against CCl4 induced oxidative stress and hepatic fibrosis, has a marked inhibitory effect on S.aureus proliferation. It increased the level of Nrf2/ARE, and HO-1, inhibit the formation of ROS, cytochrome c release, activation of caspase-3 and 9, and suppressed the up-regulation of Bax.

Clofilium tosylate is a potassium channel blocker. It induces apoptosis of human promyelocytic leukemia (HL-60) cells via Bcl-2-insensitive activation of caspase-3.

Q-VD-OPH (Quinoline-Val-Asp-Difluorophenoxymethylketone) is a pan-caspase inhibitor with potent antiapoptotic properties.

1. Orientin (Luteolin-8-glucoside) may be regarded as a candidate therapeutic agent for treatment of vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway. 2. Orientin protects vascular barrier integrity by inhibiting hyperpermeability, expression of CAMs, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases. 3. Orientin has neuroprotection effect by the intracellular mediation of caspase activity; may alleviate cognitive deficits and oxidative stress in AD mice; can exert antidepressant-like effects on CUMS mice, specifically by improving central oxidative stress, neurotransmission, and neuroplasticity.

Polyphyllin D induces apoptosis via the mitochondrial apoptotic pathway as evidenced by decreased Bcl-2 expression levels, disruption of MMP and increased Bax, cytochrome C, and cleaved-caspase-3 levels. Polyphyllin D has an anti-angiogenic effect. Polyphyllin D has toxicity in human RBCs as well as its underlying mechanism for the hemolysis and eryptosis/erythroptosis. Polyphyllin D has strong anticancer activity, can overcome drug resistance in R-HepG2 cells and elicit programmed cell death via mitochondrial dysfunction.

PF-543 (Sphingosine Kinase 1 Inhibitor II), a novel sphingosine-competitive inhibitor of SphK1, inhibits SphK1 with IC50 of 2.0 nM and Ki of 3.6 nM.

1. Glaucocalyxin A (Leukamenin F)-SBE-β-CD could be useful with a better solubility and sustained function in drug delivery. 2. Glaucocalyxin A activates caspase-3, decreases BAD phosphorylation, and reduces the expression of X-linked inhibitor of apoptosis protein. 3. Glaucocalyxin A inhibits Akt phosphorylation, suppresses proliferation, and promotes apoptosis in a dose-dependent manner, but not in normal glial cells. 4. Glaucocalyxin A inhibits collagen-stimulated tyrosine phosphorylation of Syk, LAT, and phospholipase Cγ2, the signaling events in collagen receptor GPⅥ pathway. 5. Glaucocalyxin A could potentially be developed as an antiplatelet and antithrombotic agent, can inhibit platelet p-selectin secretion and integrin activation by convulxin, is a GPVI selective ligand.

Dihydrocapsaicin (CCRIS1589) is isolated from Capsicum fruit. Capsaicin is the primary active component of the heat and pain-eliciting lipid soluble fraction of the Capsicum pepper. Like capsaicin, dihydrocapsaicin is an irritant. Capsaicin is found in natural hot pepper extracts along with a number of impurities, including dihydrocapsaicin and several lesser impurities. Separation by HPLC is required in order to obtain pure dihydrocapsaicin. Dihydrocapsaicin represents about 10% of the compound present in commercial preparations purporting to be pure capsaicin, but it has about the same pungency as capsaicin. VR1 (vanilloid receptor 1) is a heat activated calcium ion channel which functions as a part of the normal nociceptive pain pathway. Capsaicin elicits a sensation of burning pain by activation of VR1 on small, non-myelinated polymodal C-type nociceptive nerve fibers. The potency of dihydrocapsaicin at VR1 appears equivalent to capsaicin. Antioxidant. Reduces oxidation of serum lipids. Mutagenic. Dihydrocapsaicin is an activator of VR1.

1. Ginkgetin has anti-influenza virus and anti-fungal activities. 2. Ginkgetin has anti-inflammatory activity, can down-regulates COX-2 induction in vivo against skin inflammatory responses. 3. Ginkgetin is a good STAT3 inhibitor and may be a useful lead

Rottlerin (NSC-56346) is a natural product purified from Mallotus Philippinensis and is a specific PKC inhibitor (IC50: PKCδ of 3-6 μM, PKCα,β,γ of 30-42 μM, PKCε,η,ζ of 80-100 μM). Rottlerin causes apoptosis via caspase 3 activation.

1. Cornuside (Comuside) has immunomodulatory activity . 2. Cornuside suppresses expression levels of cytokine-induced proinflammatory and adhesion molecules in the human endothelial cells. 3. Cornuside can treat myocardial I/R and protect the liver from CCl4-induced acute hepatotoxicity, by reducing oxidative stress and suppressing inflammatory responses. 4. Cornuside has anti-inflammatory activity by downregulations of iNOS and COX-2 due to NF-κB inhibition as well as the negative regulation of ERK1/2, p38, and JNK1/2 phosphorylations in RAW 264.7 cells. 5. Cornuside has protective potential against cerebral ischemic injury, may be due to the suppression of intracellular Ca(2+) elevation and caspase-3 activity, and improvements in mitochondrial energy metabolism and antioxidant properties.

PF-543 hydrochloride (PF-543) inhibits SphK1 with a K(i) of 3.6 nM, is sphingosine-competitive and is more than 100-fold selective for SphK1 over the SphK2 isoform.

Talabostat (PT100, Val-boroPro) is a potent, nonselective and orally available dipeptidyl peptidase IV (DPP-IV) inhibitor with a Ki of 0.18 nM. Talabostat is a nonselective DPP-IV inhibitor, inhibiting DPP8/9, FAP, DPP2 and some other DASH family enzymes essentially as potently as it inhibits DPP-IV[1]. Talabostat stimulates the immune system by triggering a proinflammatory form of cell death in monocytes and macrophages known as pyroptosis. The inhibition of two serine proteases, DPP8 and DPP9, activates the proprotein form of caspase-1 independent of the inflammasome adaptor ASC[2]. Talabostat competitively inhibits the dipeptidyl peptidase (DPP) activity of FAP and CD26/DPP-IV, and there is a high-affinity interaction with the catalytic site due to the formation of a complex between Ser630/624 and the boron of talabostat[3]. Talabostat can stimulate immune responses against tumors involving both the innate and adaptive branches of the immune system. In WEHI 164 fibrosarcoma and EL4 and A20/2J lymphoma models, PT-100 causes regression and rejection of tumors. The antitumor effect appears to involve tumor-specific CTL and protective immunological memory. Talabostat treatment of WEHI 164-inoculated mice increases mRNA expression of cytokines and chemokines known to promote T-cell priming and chemoattraction of T cells and innate effector cells[3]. Talabostat treated mice show significant less fibrosis and FAP expression is reduced. Upon PT100 treatment, significant differences in the MMP-12, MIP-1α, and MCP-3 mRNA expression levels in the lungs are also observed. Treatment with PT100 in this murine model of pulmonary fibrosis has an anti-fibro-proliferative effect and increases macrophage activation[4]. [1]. Connolly BA, et al. Dipeptide boronic acid inhibitors of dipeptidyl peptidase IV: determinants of potencyand in vivo efficacy and safety. J Med Chem. 2008 Oct 9;51(19):6005-13. [2]. Okondo MC, et al. DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis. Nat Chem Biol. 2017 Jan;13(1):46-53. [3]. Adams S, et al. PT-100, a small molecule dipeptidyl peptidase inhibitor, has potent antitumor effects and augments antibody-mediated cytotoxicity via a novel immune mechanism. Cancer Res. 2004 Aug 1;64(15):5471-80. [4]. Egger C, et al. Effects of the fibroblast activation protein inhibitor, PT100, in a murine model of pulmonary fibrosis. Eur J Pharmacol. 2017 Aug 15;809:64-72.

Crocin (Gardenia Yellow) is a water-soluble carotenoid pigment of saffron (Crocus sativus L. ) that has been used as a spice for flavoring and coloring food preparations, and in Chinese traditional medicine as an anodyne or tranquilizer. Crocin suppresses tumor necrosis factor (TNF)alpha-induced apoptosis of pheochromocytoma (PC12) cells by modulating mRNA expressions of Bcl-2 family proteins, which trigger downstream signals culminating in caspase-3 activation followed by cell death. Crocin prevented the activation of nSMase by enhancing the transcription of gamma-glutamylcysteinyl synthase, which contributes to a stable glutathione supply that blocks the activity of nSMase.

ExcisaninA may be a potent inhibitor of AKT signaling pathway in tumor cells, it can inhibit invasion by suppressing MMP-2 and MMP-9 expression, it may be a potential anti-metastatic chemotherapeutic agent for the treatment of breast cancer. Excisanin A shows comparable inhibitory effects on the LPS-induced production of NO and PGE2, and activation of NF-kappaB without affecting cell viability.Excisanin A induces apoptosis in colon cancer cell line SW620 as determined by Annexin V staining, the cleavage of caspase-3 and the proteolytic degradation of poly (ADP-ribose) polymerase (PARP).

1. Ilexsaponin A (Ilexsaponin A1) shows protective effects on ischemia-reperfusion-induced myocardial injury through anti-apoptotic pathway.