caspase 9

Caspase-9 Inhibitor III (Ac-LEHD-cmk) 是一种 caspase-9抑制剂。Caspase-9 Inhibitor III 对局部缺血-重新灌注诱导的心肌损伤表现出保护作用。

Caspase-3 Inhibitor I (N-acetyl-asp-glu-val-asp-al) 是 Caspase-3 的特异性抑制剂。

Procyanidin C1 是一种天然多酚，可造成 DNA 损伤，细胞周期停滞，诱导凋亡。它降低癌细胞中 Bcl-2 的蛋白水平，增强 BAX，caspase 3 和 9 的表达。

Rimiducid 是一种可渗透脂质的他克莫司类似物，是一种二聚剂，通过交联 FKBP 结构域起作用。它将 Caspase 9 自杀开关二聚化并迅速诱导细胞凋亡。

2-methoxycinnamaldehyde 是一种肉桂中的天然产物。它能通过使线粒体膜电位 (ΔΨm) 损失 、激活 caspase-3 和 caspase-9，来抑制细胞增殖和诱导细胞凋亡，具有抗肿瘤活性。它还能抑制血小板衍生生长因子诱导的 HASMC 迁移。

Terfenadine ((±)-Terfenadine) 是一种hERG 开放通道抑制剂，IC50为 204 nM。它也是一种 H1 组胺受体拮抗剂，通过调节Ca2+稳态在黑素瘤细胞中起到有效的细胞凋亡诱导作用。 Terfenadine 诱导 ROS 依赖性细胞凋亡，同时激活Caspase-4，-2，-9。

Arg-Gly-Asp-Ser acetate 是一种整合素结合序列，可直接特异性结合 pro-caspase-8、pro-caspase-9 和 pro-caspase-3，但不结合 pro-caspase-1。它抑制整合素受体功能。

EF24 (3,5-Bis[(2-fluorophenyl)Methylene]-4-piperidinone) 是姜黄素类似物，口服生物利用度高，抗肿瘤作用强。它可增强活化的 Caspase3 及 Caspase9 的水平，并抑制 MEK1 及 ERK 的磷酸化形式的表达。它可以抑制口腔鳞状细胞癌细胞的 MAPK ERK 信号通路，从而发挥抗肿瘤作用。

NS3694 是一种凋亡抑制剂，可抑制凋亡小体形成和半胱天冬酶活化。

Fraxetin (7,8-dihydroxy-6-methoxy coumarin) 是从秦皮中分离出来的一种天然产物，可诱导细胞凋亡，具有抗肿瘤、抗氧化作用和抗炎作用。

Q-VD-OPH (Quinoline-Val-Asp-Difluorophenoxymethylketone) 是一种具有强效抗凋亡特性的泛半胱天冬酶抑制剂。它可抑制 HIV 感染，能透过血脑屏障。

ML-9 是 Akt 激酶的一种选择性强效抑制剂，可抑制肌球蛋白轻链激酶 (MLCK) 和基质相互作用分子1(STIM1) 活性。它通过刺激自噬小体的形成并抑制其降解来诱导自噬。它抑制 MLCK，PKA 和 PKC 活性，Ki 值分别为 4、32 和 54 μM。

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.

TC11 (1H-Isoindole-1,3(2H)-dione, 5-amino-2-[2,6-bis(1-methylethyl)phenyl]-TC11) 是一种有效的肿瘤细胞增殖抑制剂，并通过激活 caspase-3、8 和 9 诱导细胞凋亡。在长时间有丝分裂阻滞期间，它诱导 MCL1降解导致凋亡。它作为苯酞酰亚胺衍生物在结构上与免疫调节药物相关。

NLRP3-IN-9 (INF-4E) 是 NLRP3 ATPase 和 caspase-1 的抑制剂。 NLRP3-IN-9 通过不可逆地捕获硫醇亲核体发挥作用，以时间和浓度依赖性方式防止 ATP 和尼日利亚菌素触发的人 THP-1 细胞焦亡。

Ac-AAVALLPAVLLALLAP-LEHD-CHO 是半胱天冬酶4、5和9的抑制剂，能够对Neocarzinostatin处理的MCF-7细胞展现保护效果。

Nemorosone is a polycyclic polyprenylated acylphloroglucinol (PPAP) originally isolated from C. rosea that has antiproliferative properties.1 Nemorosone inhibits growth of NB69, Kelly, SK-N-AS, and LAN-1 neuroblastoma cells (IC50s = 3.1-6.3 μM), including several drug-resistant clones, but not MRC-5 human embryonic fibroblasts (IC50 = >40 μM).2 It increases DNA fragmentation in LAN-1 cells in a dose-dependent manner, and decreases N-Myc protein levels and phosphorylation of ERK1/2 by MEK1/2. Nemorosone also inhibits growth of Capan-1, AsPC-1, and MIA-PaCa-2 pancreatic cancer cells (IC50s = 4.5-5.0 μM following a 72-hour treatment) but not human dermal and foreskin fibroblasts (IC50s = >35 μM).1 It induces apoptosis, abolishes the mitochondrial membrane potential, and increases cytosolic calcium concentration in pancreatic cancer cells in a dose-dependent manner. Nemorosone activates the caspase cascade in a dose-dependent manner and inhibits cell cycle progression, increasing the proportion of cells in the G0/G1 phase, in both neuroblastoma and pancreatic cancer cells.1,2 Nemorosone (50 mg/kg, i.p., per day) also reduces tumor growth in an MIA-PaCa-2 mouse xenograft model.3References1. Holtrup, F., Bauer, A., Fellenberg, K., et al. Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR). Br. J. Pharmacol. 162(5), 1045-1059 (2011).2. Díaz-Carballo, D., Malak, S., Bardenheuer, W., et al. Cytotoxic activity of nemorosone in neuroblastoma cells. J. Cell. Mol. Med. 12(6B), 2598-2608 (2008).3. Wold, R.J., Hilger, R.A., Hoheisel, J.D., et al. In vivo activity and pharmacokinetics of nemorosone on pancreatic cancer xenografts. PLoS One 8(9), e74555 (2013). Nemorosone is a polycyclic polyprenylated acylphloroglucinol (PPAP) originally isolated from C. rosea that has antiproliferative properties.1 Nemorosone inhibits growth of NB69, Kelly, SK-N-AS, and LAN-1 neuroblastoma cells (IC50s = 3.1-6.3 μM), including several drug-resistant clones, but not MRC-5 human embryonic fibroblasts (IC50 = >40 μM).2 It increases DNA fragmentation in LAN-1 cells in a dose-dependent manner, and decreases N-Myc protein levels and phosphorylation of ERK1/2 by MEK1/2. Nemorosone also inhibits growth of Capan-1, AsPC-1, and MIA-PaCa-2 pancreatic cancer cells (IC50s = 4.5-5.0 μM following a 72-hour treatment) but not human dermal and foreskin fibroblasts (IC50s = >35 μM).1 It induces apoptosis, abolishes the mitochondrial membrane potential, and increases cytosolic calcium concentration in pancreatic cancer cells in a dose-dependent manner. Nemorosone activates the caspase cascade in a dose-dependent manner and inhibits cell cycle progression, increasing the proportion of cells in the G0/G1 phase, in both neuroblastoma and pancreatic cancer cells.1,2 Nemorosone (50 mg/kg, i.p., per day) also reduces tumor growth in an MIA-PaCa-2 mouse xenograft model.3 References1. Holtrup, F., Bauer, A., Fellenberg, K., et al. Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR). Br. J. Pharmacol. 162(5), 1045-1059 (2011).2. Díaz-Carballo, D., Malak, S., Bardenheuer, W., et al. Cytotoxic activity of nemorosone in neuroblastoma cells. J. Cell. Mol. Med. 12(6B), 2598-2608 (2008).3. Wold, R.J., Hilger, R.A., Hoheisel, J.D., et al. In vivo activity and pharmacokinetics of nemorosone on pancreatic cancer xenografts. PLoS One 8(9), e74555 (2013).

CTL-12是一种Fatty Acid Synthase (FASN)抑制剂（IC50: 2.5 μM），能够诱导apoptosis。它使细胞周期在Sub-G1/S期停滞并增加caspase-9和凋亡标志物Bax的表达，同时减少抗凋亡标志物Bcl-xL的水平。CTL-12通过抑制de novo脂肪酸合成，切断了肿瘤细胞的代谢需求，是乳腺癌和结直肠癌研究中的重要工具。

Ganoderic acid T1是Ganoderic acid T的去乙酰化衍生物，具有促进癌细胞凋亡(apoptosis)的功能。它通过降低线粒体膜电位以及激活caspase-9和caspase-3来引发细胞凋亡，并增加细胞内ROS的产生，从而表现出促氧化活性和细胞性毒作用，同时减弱抗氧化防御系统。

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).

Ac-LEHD-CHO 是 caspase8 9 的抑制剂，可防止 GalN TNF-α 诱导的肝毒性和肝细胞凋亡 (apoptosis)。

Arg-Gly-Asp-Ser (TFA) 为整联蛋白结合序列，专门抑制整联蛋白受体(integrin receptor)功能。它能够直接且特异性地与pro-caspase-8、pro-caspase-9和pro-caspase-3结合，而不与pro-caspase-1发生作用。

Z-LEHD-FMK 是一种具有选择性和有效性的 caspase-9 抑制剂，可防减轻再灌注损伤，减缓细胞凋亡。Z-LEHD-FMK 具有抗肿瘤和神经保护活性，可提高体外生产的水牛 （Bubalus bubalis） 植入前胚胎的产量并改变细胞应激反应。

Lucidenic acid B (Lucidenicacid B) 是从灵芝中提取得到的天然化合物，可诱导caspase-9 和 caspase-3 的活化和 PARP 的裂解，可通过线粒体介导诱导人白血病细胞凋亡 。 Lucidenic acid B通过灭活MAPK ERK信号转导途径和降低NF-kappaB和AP-1的结合活性来抑制PMA诱导的人肝癌细胞侵袭。。Lucidenic acid B 对细胞周期和坏死细胞没有影响。

Z-LEHD-FMK TFA is a specific and irreversible inhibitor of caspase-9, offering protection against detrimental reperfusion injury and moderating apoptosis. Additionally, Z-LEHD-FMK TFA demonstrates its neuroprotective potential in a rat model of spinal cord trauma.

SCR7 是一种特异性 DNA 连接酶 IV 抑制剂，可阻断非同源末端连接。它是一种不稳定的形式，可以自动循环成​​稳定形式的 SCR7 pyrazine。它也是CRISPR/Cas9的增强子，可提高 Cas9 介导的同源性定向修复的效率。它诱导细胞凋亡并具有抗癌活性。

NVP 231 是一种强效、特异、可逆的神经酰胺激酶抑制剂，IC50值为12 nM，可竞争性地抑制神经酰胺与 CerK 的结合。它通过增加 DNA 片段和 caspase-3 和 caspase-9 的裂解来诱导细胞凋亡。

MPT0B214 is a novel and potent microtubule inhibitor with potential anticancer activity. MPT0B214 inhibited tubulin polymerization through strongly binding to the tubulin's colchicine-binding site and had cytotoxic activity in a variety of human tumor cell lines. After treatment with MPT0B214, KB cells were arrested in the G2-M phase before cell death occurred, which were associated with upregulation of cyclin B1, dephosphorylation of Cdc2, phosphorylation of Cdc25C and elevated expression of the mitotic marker MPM-2. Furthermore, the compound induced apoptotic cell death through mitochondria/caspase 9-dependent pathway. Notably, several KB-derived multidrug-resistant cancer cell lines were also sensitive to MPT0B214 treatment. ( PLoS One. 2013;8(3):e58953).

DAT-230 is a promising microtubule inhibitor that has great potential for the treatment of fibrosarcoma in vitro and in vivo. DAT-230 exhibited potent anti-proliferative activity against various cancer cells. DAT-230 -treatment in HT-1080 cells resulted in microtubule de-polymerization and G2 M phase arrest preceding apoptosis. Phosphor-cdc2 (thr14 tyr15) reduction, cyclin B1 accumulation and aberrant spindles denoted the cyclin B1-cdc2 complex active and M phase arrest in HT-1080 cells treated with DAT-230. Apoptosis induced by DAT-230 was related with the activation of caspase-9, caspase-3 and PARP cleavage, which were at the downstream of mitochondria.

Isoerysenegalensein E shows anti-estrogenic activity comparable to that of 4-hydroxytamoxifen, a typical estrogen receptor antagonist. It shows significant cytotoxicity against HL-60 cells, it induces apoptosis in HL-60 cells through activation of the cas

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

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

Puerarin 6''-O-Xyloside 是从葛根中分离得到的一种天然产物，可诱导线粒体介导的细胞凋亡通路，有抗炎和抗癌活性。

Anticancer agent 58 对多种癌细胞具有抑制活性，特别是在 A549 和 T24 细胞中，IC50分别为 0.6 μM 和 0.7 μM。Anticancer agent 58 通过激活 caspase3/8/9活性诱导细胞凋亡 (apoptosis)，也诱导 Ca2+和 ROS 水平升高。Anticancer agent 58 在 T24 异种移植小鼠模型中能显著抑制肿瘤生长。

SCR7 pyrazine (SCR7) 是一种 DNA 连接酶 IV 抑制剂，以连接酶 IV 依赖的方式阻断非同源末端连接。它也是 CRISPR Cas9的增强子，可提高 Cas9 介导的同源性定向修复的效率。它诱导细胞凋亡，具有抗癌活性。

HDAC-IN-53是一种口服活性的选择性HDAC1-3抑制剂，其IC50分别为47 nM、125 nM和450 nM。该化合物不针对II类HDAC(HDAC4、5、6、7、9；IC50>10 μM)展现抑制作用。HDAC-IN-53能够诱导caspase依赖的细胞凋亡并在裸鼠中显著抑制人肿瘤异种移植物生长，同时抑制携带MC38结肠癌的免疫活性小鼠的肿瘤发展。

MPT0B206 is a novel tubulin polymerization inhibitor. MPT0B206 induced G2/M cell cycle arrest and the appearance of the mitotic marker MPM-2 in K562 and K562R cells, which is associated with the upregulation of cyclin B1 and the dephosphorylation of Cdc2.

CGP74514A is a CDK1 inhibitor with potential anticancer activity. In U937 cells, CGP74514A - induced apoptosis (5 microM) became apparent within 4 hr and approached 100% by 24 hr. The pan- caspase inhibitor Boc-fmk and the caspase-8 inhibitor lETD-fmk opposed CGP74514A -induced caspase-9 activation and PARP degradation, but not cytochrome c or Smac/DIABLO release. CGP74514A -mediated apoptosis was substantially blocked by ectopic expression of full-length Bel- 2, a loop-deleted mutant Bcl-2, and Bcl-x(L). CGP74514A treatment (5 microM; 18 hr) resulted in increased p21(CIP1) expression, p27(KIP1) degradation, diminished E2F1 expression, and dephosphorylation of p34(CDC2). It also induced early (i.e., within 2 hr) inhibition of CDK1 activity and dephosphorylation of pRb, followed by pRb degradation, but did not block pRb phosphorylation at CDK2- and CDK4- specific sites. These findings indicate that the selective CDK1 inhibitor, CGP74514A , induces complex changes in cell cycle......

Furowanin A shows significant cytotoxicity against HL-60 cells, it induces that Caspase-9 and caspase-3 inhibitors suppresses apoptosis.

5,7-Dihydroxychromone (5,7-Dihydroxy-4H-Chromen-4-One) 是一种Cudrania tricuspidata 的提取物，通过激活 Nrf2 ARE 信号对 6-OHDA 诱导的氧化应激和细胞凋亡发挥神经保护作用。它抑制 6-OHDA 诱导的 SH-SY5Y 细胞中活化的caspase-3，caspase-9以及切割的PARP 表达。

Embelin (Embelic acid) 是从日本 Ardisia 草药中分离出来的一种非肽类细胞渗透性XIAP 抑制剂，诱导口腔鳞癌细胞自噬和凋亡。它阻断 NF-kappaB 信号通路，从而抑制 NF-kappaB 调节的抗凋亡和转移基因产物。在高水平 XIAP 的前列腺癌细胞中抑制细胞生长，诱导凋亡，并激活 caspase-9。

HA-14-1, a small molecule, binds the surface pocket of Bcl-2 proteins (IC50= ~ 9 µM), including Bcl-xl and Bcl-W, and disrupts their interaction with the Bak peptide. This action induces apoptosis by activating Apaf-1 and caspase-9 and -3. Additionally, HA-14-1 effectively induces apoptosis in human acute myeloid leukemia (HL-60) cells, with a 50 µM concentration resulting in a 90% loss of cell viability.

Z-ATAD-FMK 是一种caspase-12的抑制剂。它通过抑制caspase-12的活性来减少caspase-9的活性，从而阻止内质网应激引发的细胞凋亡。

MX1013, a dipeptide pan-caspase inhibitor, inhibits caspase-1, -3, -6, -7, -8, and -9.

Dexamethasone sodium succinate is the acetate salt form of dexamethasone, which is a synthetic glucocorticoid; it combines high anti-inflammatory effects with low mineralocorticoid activity. At high doses (e.g. 40 mg), it reduces the immune response. Dexamethasone acetate (NEOFORDEX®) is indicated in adults for the treatment of symptomatic multiple myeloma in combination with other medicinal products. Dexamethasone has been shown to induce multiple myeloma cell death (apoptosis) via a down-regulation of nuclear factor-κB activity and an activation of caspase-9 through second mitochondria-derived activator of caspase (Smac; an apoptosis promoting factor) release. Prolonged exposure was required to achieve maximum levels of apoptotic markers along with increased caspase-3 activation and DNA fragmentation. Dexamethasone also down-regulated anti apoptotic genes and increased IκB-alpha protein levels. Dexamethasone apoptotic activity is enhanced by the combination with thalidomide......

Ac-LEHD-AMC is a fluorogenic substrate for caspase-9.[1] Upon cleavage by caspase-9, 7-amino-4-methylcoumarin (AMC) is released and its fluorescence can be used to quantify caspase-9 activity. AMC displays excitation emission maxima of 340-360 440-460 nm, respectively.

CTL-06是一种Fatty Acid Synthase (FASN)抑制剂，具有3 μM的IC50，能够诱发细胞凋亡。CTL-12导致细胞周期在Sub-G1/S期停滞，并增加caspase-9和凋亡标志物Bax的表达，减少抗凋亡标志物Bcl-xL的表达。此外，CTL-12通过抑制脂肪酸的从头合成，剥夺肿瘤细胞代谢所需，主要用于乳腺癌和结直肠癌的研究。

Aviculin 是一种木聚糖苷，是一种有效的抗癌剂 (anticanceragent)。Aviculin 可降低 MCF-7 细胞代谢活性到 50% 以下，IC50为 75.47 μM。Aviculin 通过内在凋亡途径诱导乳腺癌细胞凋亡 (apoptosis)。Aviculin 增加了 caspase-9、caspase-7和 PARP 的表达。Aviculin 使 Bax/Bcl-2 的比值升高。