cascade

Diclofenac (Diclofenacum) 是一种具有抗炎活性的非甾体苯乙酸衍生物，是 COX 抑制剂，在 CHO 细胞中，对人 COX-1 和 COX-2 的 IC50值分别为 4 和 1.3 nM。它对绵羊 COX-1 和 COX-2 的 IC50值分别为 5.1 μM，0.84 μM。它通过活化 caspase 级联反应来诱导神经干细胞凋亡。

Diclofenac diethylamine 是非选择性抗炎剂，通过活化 caspase 级联反应来诱导神经干细胞凋亡。它是一种COX 抑制剂，在 CHO 细胞中，对人COX-1和COX-2的IC50值分别为 4 和 1.3 nM。它对绵羊COX-1和COX-2的IC50值分别为 5.1 μM 和0.84 μM。

Diclofenac sodium (GP 45840) 是一种非选择性抗炎剂，是 COX 抑制剂，在 CHO 细胞中，对人 COX-1 和 COX-2 的 IC50值分别为 4 和 1.3 nM。它对绵羊 COX-1 和 COX-2 的 IC50值分别为 5.1 μM，0.84 μM。它通过活化 caspase 级联反应来诱导神经干细胞凋亡。

Diclofenac Potassium (CGP-45840B) 是一种非甾体抗炎药，用于减轻炎症并在某些情况下作为镇痛剂减轻疼痛。它通过活化 caspase 级联反应来诱导神经干细胞凋亡。它是一种COX 抑制剂，在 CHO 细胞中，对人 COX-1 和 COX-2 的IC50值分别为 4 和 1.3 nM。它对绵羊 COX-1 和 COX-2 的IC50值分别为 5.1 μM 和0.84 μM。

Flufenoxuron（氟虫脲）是一种苯甲酰脲类杀虫剂，能抑制昆虫体内几丁质的合成，有一定毒性，通过靶向小鼠线粒体抑制睾丸细胞的增殖。

3,6-Dihydroxyflavone 是一种抗癌剂。它能够提高细胞内氧化应激和脂质过氧化。它是能够根据剂量和时间依赖性地降低细胞活力，并活化半胱天冬酶级联、切割聚 (ADP-核糖) 聚合酶 (PARP) 诱导细胞凋亡。

RSK2-IN-3 (Compound 26) 是一种共价的、可逆的 RPS6KA3 (RSK2) 激酶抑制剂。

Melagatran 是一种可以口服的、直接合成的凝血酶抑制剂，除凝血酶外，Melagatran美拉加群不需要内源性辅助因子，也不会与凝血级联反应中的任何其他酶或纤维蛋白溶解酶具有显着的相互作用。

SF5 是一种通过 JNK-p53-caspase 凋亡级联的凋亡通路抑制剂。

Monensin is an antiprotozoal agent produced by Streptomyces cinnamonensis. It has an inhibitory effect on the Wnt/β-catenin signaling cascade. Monensin is a prospective anticancer drug for the therapy of neoplasia with deregulated Wnt signaling.

Jasmonic acid (JA) 是一种植物激素，也是植物生长调节剂，参与植物迫防御和生长发育。Jasmonic acid 在信号传导过程中起着很重要的作用，诱导 MAP 激酶级联通路和钙通道发挥作用。

TAC(TERT activator compound)是一种TERT(Telomerase reverse transcriptase)激活剂，能通过 MEK/ERK/AP-1 级联途径增强TERT的转录活性，在原代人细胞和自然衰老小鼠中促进端粒的合成，减少细胞衰老和炎症细胞因子，减轻神经炎症等等。

Microtubule destabilizing agent-2 (Compound 21) 是一种选择性靶向微管蛋白的口服抗肿瘤化合物。它通过破坏微管蛋白稳定性和抑制微管聚合，导致人肿瘤细胞在G0/G1期停滞，并通过激活Caspase级联途径诱导细胞凋亡 (Apoptosis)。此外，Microtubule destabilizing agent-2 还具有抗炎特性，能够在体外抑制TNF-α和IL-6的产生，并可抑制小鼠异种移植瘤的生长。

SKF-96365 hydrochloride (SKF96365) 是store-operated Ca2+entry 抑制剂，也是TRP channel 阻滞剂。它显著抑制豚鼠离体心脏 hERG、hKCNQ1/hKCNE1、hKir2.1 和 hKv4.3 电流，延长QTc 间期。它通过诱导结直肠癌细胞的细胞周期阻滞和凋亡起抗肿瘤作用。

Prothrombin (coagulation factor II) is produced in the liver and is post-translationally modified in a vitamin K-dependent reaction that converts ten glutamic acids on prothrombin into gamma-carboxyglutamic acid. Prothrombin is proteolytically cleaved to

Alloferon 3 is a natural peptide that mediates signaling by the NF-kappa B pathway to enhance the recognition of viral and tumor antigens. It is known to induce the production of endogenic interferons that promote a cascade of defense responses and also e

EP6 is an inhibitor of 5-lipoxygenase (5-LO), which is a crucial enzyme of the arachidonic acid (AA) cascade and catalyzes the formation of bioactive leukotrienes (LTs) which are involved in inflammatory diseases and allergic reactions.

Pimecrolimus (SDZ-ASM 981) 是一种免疫亲和素配体，能与胞质受体特异性的结合。

Angstrom6 (A-6 peptide) 是一种从单链尿激酶纤溶酶原激活剂(scuPA)中提取的 8 肽，它能干扰 uPA/uPAR 级联反应并抑制下游效应。Angstrom6 具有抗肿瘤活性，能通过与 CD44 结合并调节 CD44 介导的细胞信号传导，抑制肿瘤细胞的迁移、侵袭和转移。

Fascaplysin is a cyclin D kinase 4/ cyclin D1 inhibitor (IC50 = 0.35 μM). Fascaplysin induces caspase mediated crosstalk between autophagy and apoptosis through the inhibition of PI3K/AKT/mTOR signaling cascade in human leukemia HL-60 cells.

PtdIns-(3,4,5)-P3 (PIP3) serves as an anchor for the binding of signal transduction proteins bearing pleckstrin homology (PH) domains such as phosphatidylinositol 3-kinase (PI3K) or PTEN. Protein binding to PIP3 is important for cytoskeletal rearrangement and membrane trafficking and initiates an intricate signaling cascade that has been implicated in cancer. 3,5-dimethyl PIT-1 is a dimethyl analog of PIT-1, the selective inhibitor of PIP3/Akt PH domain binding, that is designed for more favorable solubility in vivo. 3,5-dimethyl PIT-1 inhibits PI3K/Akt signaling (IC50 = 27 μM), suppressing PI3K-PDK1-Akt-dependent phosphorylation, which has been shown to reduce cell viability and induce apoptosis in PTEN-deficient U87MG glioblastoma cells (IC50 = 36 μM). 4T1 breast cancer growth is significantly attenuated in BALB/c mice with a dose of 1 mg/kg of 3,5-dimethyl PIT-1 per day.

Desmethylanethol trithione (ADT-OH) 是合成硫化氢的供体。它利用上调 FADD 诱导细胞凋亡，并对体内黑色素瘤的形成具有一定的抑制作用，可用于研究癌症疾病。

The phosphatidylinositol (PtdIns) phosphates represent a small percentage of total membrane phospholipids. However, they play a critical role in the generation and transmission of cellular signals. PtdIns-(1,2-dioctanoyl) is a synthetic analog of natural phosphatidylinositol (PtdIns) containing C8:0 fatty acids at the sn-1 and sn-2 positions. The compound features the same inositol and diacyl glycerol (DAG) stereochemistry as that of the natural compound. The short fatty acid chains of this analog, compared to naturally-occurring PtdIns, gives it different physical properties including high solubility in aqueous media. PtdIns are phosphorylated to mono- (PtdIns-P; PIP), di- (PtdIns-P2; PIP2), and triphosphates (PtdIns-P3; PIP3). Hydrolysis of PtdIns-(4,5)-P2 by phosphoinositide (PI)-specific phospholipase C generates inositol triphosphate (IP3) and DAG which are key second messengers in an intricate biochemical signal transduction cascade.

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).