caspase-9

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

Duocarmycin A, an antitumor antibiotic, is a DNA alkylator and efficiently alkylates adenine N3 at the 3′ end of AT-rich sequences in the DNA. Duocarmycin A, as a chemotherapeutic agent, results in HLC-2 cells typically apoptotic changes.

Caspase-9 Inhibitor III (Ac-LEHD-cmk), a caspase-9 inhibitor, demonstrates protective effects against ischemia-reperfusion-induced myocardial injury.

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.

Fenbufen (Lederfen) is a non-steroidal anti-inflammatory drug used primarily to treat inflammation in osteoarthritis, ankylosing spondylitis, and tendinitis. It can also be used to relieve backaches, sprains, and fractures. Fenbufen is available as a capsule or tablet sold with the brand names Cepal, Cinopal, Cybufen, Lederfen, and Reugast. Fenbufen acts by preventing cyclooxygenase from producing prostaglandins which can cause inflammation.

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

ML-9 suppresses MLCK, PKA, and PKC activity with Ki values of 4, 32, and 54 μM, respectively. ML-9 is a selective and effective inhibitor of Akt kinase, inhibits myosin light-chain kinase (MLCK), and stromal interaction molecule 1 (STIM1) activity. ML-9 causes autophagy by stimulating autophagosome formation and inhibiting their degradation.

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

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.

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.

Embelin (Embelic acid), isolated from the Japanese Ardisia herb, is an inhibitor of the X-linked inhibitor of apoptosis (IC50: 4.1 uM).

Procyanidin C1 is a natural polyphenol that causes DNA damage, cell cycle arrest, and apoptosis induction. It reduces Bcl-2 protein levels and enhances the expression of BAX, caspase 3, and 9 in cancer cells.

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

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.

Terfenadine ((±)-Terfenadine) is a prodrug metabolized by intestinal CYP3A4 into fexofenadine, an active selective histamine H1-receptor antagonist that possesses antihistaminic and non-sedative effects.

Uvarigrin induces tumor multidrug resistance cell apoptosis and triggers Caspase-9 activation. Uvarigrin is isolated from the roots of Uvaria calamistrata.

Rimiducid is a lipid-permeable tacrolimus analogue, homodimerizing an analogue of human protein fkbp12 and binding to wild-type fkbp12 with 1000-fold lower affinity. Rimiducid is a dimerizer agent that acts by cross-linking the FKBP domains. It dimerizes the Caspase 9 suicide switch and rapidly induces apoptosis.

ML132 is an effective and selective inhibitor of caspase 1 (IC50: 0.316 nM).

SCR7 pyrazine (SCR7) enhances CRISPR-Cas9-mediated homology-directed repair (HDR) efficiency in vitro up to 19-fold. Inhibits nonhomologous end-joining (NHEJ).

NVP-231 is a potent, specific and reversible CerK inhibitor(IC50=12±2 nM) that competitively inhibits ceramide binding to CerK.

MAPK-IN-3 (Compound 4a) is an antiproliferative agent demonstrating significant inhibitory effects on KYSE 30, HCT 116, and HGC 27 cell lines, with IC50 values of 0.57 μM, 3.27 μM, and 2.28 μM, respectively. This compound arrests the cell cycle via a p53-dependent mechanism and induces apoptosis through a p53-independent pathway. It reduces the expression of cell cycle-related proteins, such as Cyclin D1 and Cyclin B1, while increasing pro-apoptotic proteins like cleaved PARP, cleaved caspase-7, and cleaved caspase-9. MAPK-IN-3 also decreases anti-apoptotic proteins such as Bcl-2, elevates ROS levels in KYSE 30 cells, and enhances the expression of ROS-related MAPK pathway members, including p-ERK, p-p38, and p-JNK.

ERK1 2 inhibitor 12 (compound 76.3) is an ERK1 2 inhibitor that suppresses ERK-mediated phosphorylation of caspase-9 and p90Rsk-1 kinases. It exhibits anticancer properties and is applicable in cancer research.

EMT inhibitor-3 (compound 11i) is an epithelial-mesenchymal transition (EMT) inhibitor that effectively suppresses the proliferation, migration, and invasion of SK-N-SH neuroblastoma cells, with an IC50 value of 2.5 μM. It induces mitochondrial-mediated intrinsic apoptosis in tumor cells by enhancing the Bax Bcl-2 protein expression ratio, promoting the release of cytochrome C from mitochondria, and activating caspase 9 and caspase 3. EMT inhibitor-3 is applicable for cancer research.

TCF4 β-catenin-IN-1 (Compound 8b) is an inhibitor of TCF4 β-catenin that induces apoptosis. This compound enhances the expression of p53, caspase-3, caspase-8, caspase-9, and Bax proteins, while reducing Bcl-2 protein levels. TCF4 β-catenin-IN-1 also inhibits CYP3A4, CYP1A2, and CYP2C19, demonstrating significant cytotoxic activity in cancer cells.