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

Caspase-8-IN-1 is a potent caspase-8 inhibitor [1] .

Ac-YVAD-CMK (Ac-Tyr-Val-Ala-Asp-CMK) is a selective and irreversible inhibitor of Caspase-1 and inhibits pyroptosis, IL-1β and IL-18. Ac-YVAD-CMK shows neuroprotective and anti-inflammatory capacity.

Caspase-6-IN-1 is a novel Allosteric Inhibitor of Caspase-6 Activation, blocking the interaction between C6 and mHTT1-586.

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

Iptacopan (LNP023) is an inhibitor with high affinity for factor B.

Diclofenac Potassium (CGP-45840B) is a nonsteroidal anti-inflammatory drug taken to reduce inflammation and as an analgesic reducing pain in certain conditions.

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.

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

Belnacasan (VX-765) is an orally active IL-converting enzyme/caspase-1 inhibitor.

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.

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.

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

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.

Ac-YVAD-AOM is a selective and potent caspase-1 inhibitor showing antitumor activity and potential analgesic activity.

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.

EP1013 is a broad-spectrum selective inhibitor of Caspase used in the study of type 1 diabetes.

GS-6201 (CVT-6883) is a selective antagonist of adenosine A2B receptor. GS-6201 shows high affinity and selectivity for the human adenosine A2B receptors with a Ki of 22 nM.

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

CP-456773 (MCC950 (CP-456773) and CRID3) is an effective and specific cytokine release inhibitor and NLRP3 inflammasome inhibitor. CP-456773 inhibits IL-1β secretion and caspase 1 processing. MCC950 blocked canonical and noncanonical NLRP3 activation at nanomolar concentrations. MCC950 specifically inhibited activation of NLRP3 but not the AIM2, NLRC4 or NLRP1 inflammasomes. MCC950 reduced IL-1β production in vivo and attenuated the severity of experimental autoimmune encephalomyelitis (EAE), a disease model of multiple sclerosis.

1. Polyphyllin VI has hemostasis , expectorant , bacteriostasis, anticytotoxic, anti pregnancy kill sperm effects.

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.

JC2-11 is an inhibitory compound for inflammation.JC2-11 inhibits the recruitment domain-containing proteins NLRC 4, atypical in melanoma 2 (AIM 2) and atypical (NC) inflammatory vesicles by disrupting reactive oxygen species (ROS) production and caspase-1 activity.JC2-11 reduces caspase-1 (p20) secretion, gasdermin D (GSDMD) cleavage, IL-1β and lactate dehydrogenase (LDH) activity in inflammatory vesicles. JC2-11 reduced caspase-1 (p20) secretion, gasdermin D (GSDMD) cleavage, IL-1β and lactate dehydrogenase (LDH) release from inflammatory vesicles.

NLRP3 agonist 1 (compound 23) serves as a potent, orally active agent that activates Caspase-1 enzyme, leading to the cleavage of proinflammatory cytokines pro-IL-1β and pro-IL-18 into their active forms [1].

PB28 is a cyclohexylpiperazine derivative that functions as a potent and highly selective agonist of the sigma 2 (σ2) receptor, exhibiting a Ki (binding affinity) of 0.68 nM. At the same time, PB28 acts as an antagonist of the sigma 1 (σ1) receptor, with a Ki of 0.38 nM. PB28 demonstrates a lower affinity for other receptors. It effectively inhibits electrically evoked twitch in both the guinea pig bladder (EC50 value of 2.62 μM) and ileum (EC50 value of 3.96 μM). Moreover, PB28 exhibits the ability to modulate protein-protein interaction between SARS-CoV-2 and human cells. Additionally, PB28 triggers caspase-independent apoptosis and possesses significant antitumor activity.

QS-21, an immunostimulatory saponin, is a powerful vaccine adjuvant that stimulates both Th2 humoral and Th1 cell-mediated immune responses by interacting with antigen presenting cells (APCs) and T cells. Additionally, QS-21 activates the NLRP3 inflammasome, leading to the release of cytokines IL-1β and IL-18, which are dependent on caspase-1.

Ac-DEVD-CMK (Caspase-3 Inhibitor III) TFA is a selective and irreversible inhibitor of caspase-3, effectively preventing apoptosis triggered by elevated glucose levels or 3,20-dibenzoate (IDB). It is applicable in diverse experimental settings to impede apoptosis, as supported by references [1] [2] [3].

Skullcapflavone I has anti-inflammatory and anti-allergic potential, it can significantly inhibit LPS stimulated NO and PGE(2) release in J774A.1 macrophages and inhibit LPS induced IL-6 production in a concentration dependent manner. Skullcapflavone I se

Ac-Val-Ala-Asp-CHO (Ac-VAD-CHO) serves as a pan-caspase inhibitor and preserves mitochondrial membrane potential (MMP) while preventing the release of cytochrome c in cells subjected to hypoxia [1].

Cannflavin A, isolated from Cannabis sativa L., exhibits anti-cancer, neuroprotective, and anti-inflammatory activities by inhibiting Aβ1-42 aggregation and kynurenine-3-monooxygenase (KMO), as well as inducing apoptosis through caspase-3 cleavage [1] [2] [3] [4].

Z-YVAD-CMK is an inhibitor of both caspase-1 and caspase-3, as referenced in [1].

Anticancer Agent 141 (Compound AE), an antimycin alkaloid, exhibits inhibitory potential against HPV-infected cervical cancer. It impedes HeLa cell proliferation by arresting the cell cycle at the S phase and induces caspase-dependent apoptosis through mitochondrial disruption. This disruption activates the ROS-mediated ubiquitin-dependent proteasome system, leading to the degradation of E6/E7 oncoproteins [1].

Fluorescein-6-carbonyl-Asp(OMe)-Glu(OMe)-Val-DL-Asp(OMe)-fluoromethylketone is a cell-permeable, non-toxic inhibitor that irreversibly binds to activated caspase-3 in apoptotic cells, with its fluorescence intensity measurable via flow cytometry, microwell plate reader, or fluorescence microscopy [1].

NLRP3 agonist 2 (compound 22) is an orally active agent that activates Caspase-1 in THP1 cells [1].

Z-WEHD-FMK is a cell-permeable and irreversible inhibitor of caspase-1/5. It also shows a robust inhibitory effect on cathepsin B activity (IC50: 6 μM).

HMGB1-IN-2 (compound 15) is a selective inhibitor of the highly conserved nuclear protein HMGB1, demonstrating no inhibitory effect at an IC50 of 20.2 μM in RAW264.7 cells. At a concentration of 30 μM, HMGB1-IN-2 reduces IL-1β, TNF-α, and caspase-1 p20 levels, and inhibits NF-κB p65 phosphorylation, providing anti-apoptotic effects. In vivo, HMGB1-IN-2 at a dose of 15 mg/kg administered intraperitoneally alleviates kidney injury in a mouse model of septic acute kidney injury. Furthermore, it inhibits Huh7 and A549 cells with IC50 values of 77.0 μM and 82.0 μM, respectively [1].

Compound 14a (P2X7 receptor antagonist-4) is a P2X7R antagonist with IC50 values of 64.7 nM in humans and 10.1 nM in mice. It inhibits the activation of the NLRP3 inflammasome, which subsequently reduces the expression of caspase-1, gasdermin D, IL-1β, and IL-18 in the kidneys of mice with sepsis-induced damage [1].

Ac-DNLD-CHO (Ac-Asp-Asn-Leu-Asp-CHO) is an inhibitor of Caspase-3/7, exhibiting IC50 values of 9.89 nM and 245 nM, and approximate Ki values of 0.68 nM and 55.7 nM, respectively. This compound is utilized in the study of diseases associated with caspase-mediated apoptosis, including neurodegenerative and viral infection diseases [1].

Selaginellin has a neuroprotective effect against L-glutamate-induced neurotoxicity through mechanisms related to anti-oxidation and anti-apoptosis via scavenging reactive oxygen species and up-regulating the expression of klotho gene. Selaginellin shows

CTL-06, a Fatty Acid Synthase (FASN) inhibitor with an IC50 of 3 μM, induces apoptosis, while CTL-12 impedes cell cycle progression in the Sub-G1/S phase and modulates apoptotic and anti-apoptotic markers by upregulating caspase-9 and Bax and downregulating Bcl-xL. Additionally, CTL-12 suppresses de novo lipogenesis, curtailing the metabolic needs of tumor cells, with utilization in breast and colorectal cancer studies [1].

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.

Conatumumab (AMG 655) is a monoclonal agonist antibody targeting human death receptor 5 (DR5, TRAILR2) at Kd 1 nM for long DR5 and Kd 0.8 nM for short DR5. Conatumumab induces apoptosis in a variety of tumor types through caspase activation. Conatumumab can be used to study advanced solid tumors.

PQ401 (IGF-1R Inhibitor II) suppresses autophosphorylation of IGF-1R domain(IC50<1 μM).

Daphnetin (7,8-Dihydroxycoumarin), a natural coumarin derivative, is a protein kinase inhibitor with inhibitory for EGFR (IC50: 7.67 μM), PKA (IC50: 9.33 μM), and PKC (IC50: 25.01 μM), also exhibit anti-oxidant and anti-inflammatory activities.

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.

NS3694 is an inhibitor of apoptosis and inhibits apoptosome formation and caspase activation.

1. β,β-Dimethylacrylshikonin (Dimethylacrylshikonin) is a promising agent for developing an improved strategy for radiotherapy against tumors. (a) Injection of Dimethylacrylshikonin combined with IR treatment significantly suppressed tumor growth of the HCT-116 xenograft. (b) Dimethylacrylshikonin significantly suppressed the growth of H(22) transplantable hepatoma, and induced the activation of caspase-3 . (c) Dimethylacrylshikonin inhibited growth of gastric cancer SGC-791 cells by inducing ERK signaling pathway. 2. Dimethylacrylshikonin inhibits the proliferation of MCF-7 cells in vitro by inducing apoptosis through the downregulation of Bcl-2, upregulation of Bax and partial inactivation of the NF-κB pathway.

Isoacteoside has the anti-inflammatory effect, mediated by action on caspase-1, mitogen-activated protein kinases (c-Jun N-terminal kinase, p38, extracellular signal-regulated protein kinase) and nuclear factor-kappa B pathways.

Diclofenac (Diclofenacum) is a nonsteroidal benzeneacetic acid derivative with anti-inflammatory activity. Diclofenac binds and chelates both isoforms of cyclooxygenase (COX-1 and-2), thereby blocking the conversion of arachidonic acid to pro-inflammatory-proprostaglandins.

Diclofenac Epolamine (DHEP) is a non-steroidal anti-inflammatory agent (NSAID) with analgesic and antipyretic actions.

Diclofenac deanol is a nonsteroidal anti-inflammatory drug (NSAID) of the phenylacetic acid class with anti-inflammatory, analgesic, and antipyretic properties. Contrary to the action of many traditional NSAIDs, diclofenac inhibits cyclooxygenase (COX)-2 enzyme with greater potency than it does COX-1.

Diclofenac sodium (GP 45840) is a non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt.

5-hydroxy Diclofenac is a metabolite of the NSAID diclofenac formed by the cytochrome P450 (CYP) isoform CYP3A4. Diclofenac is a non-selective COX inhibitor. It inhibits human COX-1 and -2 with IC50 values of 0.9-2.7 and 1.5-20 μM, respectively. Diclofenac inhibits ovine COX-1 and -2 with IC50 values of 60 and 220 nM, respectively.

Diclofenac Diethylamine, a non-selective COX inhibitor, is utilized as a nonsteroidal anti-inflammatory drug (NSAID).