aspc-1

Benproperine phosphate (Pirexyl phosphate) 是一种具有口服活性的，肌动蛋白相关蛋白 2 3 复合亚基 2 (ARPC2) 抑制剂。它通过削弱 Arp2 3 功能来减弱肌动蛋白的聚合反应速率。它可抑制癌细胞迁移和肿瘤转移，有用于治疗止咳的潜力。

Amsilarotene (TAC101) 是口服有活性的合成类视黄醇，对视黄酸受体 α (RAR-α) 具有选择性亲和力，对 RAR-α 和 RAR-β 的 Ki=为 2.4 nM 和 400 nM。它可造成人胃癌、卵巢癌细胞及肝细胞癌的凋亡，可用于研究癌症。

Almorexant (ACT 078573) 是一种有效的竞争性食欲素 1 受体 (OX1) 食欲素 2 受体 (OX2) 双重拮抗剂，OX1 和 OX2 的 Ki 值分别为 1.3 和 0.17 nM。

MET PDGFRA-IN-1 (compound 8c) 作为MET和PDGFRA蛋白的抑制剂，以36 μM对MET的IC50值显示活性。该化合物能够抑制MET磷酸化并触发细胞凋亡(apoptosis)。此外，MET PDGFRA-IN-1有效抑止了多种MET阳性细胞系的增殖，包括AsPc-1、EBC-1、MKN-45、Mia-Paca-2、HT-29和K562，其IC50s分别为15.3、19.0、22.0、25.6、21.0、31.5 μM。

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).

GM 1489 is a broad-spectrum inhibitor of matrix metalloproteinases (MMPs) with Ki values of 0.002, 0.1, 0.5, 0.2, and 20 μM for MMP-1, MMP-8, MMP-2, MMP-9, and MMP-3, respectively. It reduces 5-aza-2'-deoxycytidine-induced increases in MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, and MMP-14 expression as well as cell invasion in AsPC-1, BxPC-3, Hs766T, MiaPaCa2, and PANC-1 cancer cells. Topical administration of GM 1489 (100 μg) inhibits increases in ear thickness and epidermal hyperplasia induced by phorbol 12-myristate 13-acetate and phorbol dibutyrate (PdiBu) in mice.

Almorexant hydrochloride (ACT 078573 hydrochloride) 是一种具有口服活性的双重食欲素受体（orexin receptor）拮抗剂，可阻断细胞内 Ca2+ 信号通路， 一定程度上阻断甲基苯丙胺的兴奋作用。Almorexant hydrochloride 诱导细胞凋亡，可用于研究睡眠障碍。

RIPK3-IN-3（化合物20）是一种针对受体相互作用蛋白激酶RIPK3的选择性抑制剂，其IC50为10 nM。它通过抑制p-MLKL的寡聚化作用来阻止RIPK3介导的MLKL磷酸化以及随后的坏死性凋亡。此外，RIPK3-IN-3还能降低CXCL5的分泌，并抑制AsPC-1细胞的迁移和侵袭。

Aspulvinone O is a fungal metabolite that has been found in P. variotti and has antioxidant and anticancer activities.1,2 It scavenges 2,2-diphenyl-1-picrylhydrazyl radicals in a cell-free assay (IC50 = 11.6 μM).1 Aspulvinone O inhibits aspartate transaminase 1 (GOT1; Kd = 3.32 μM) and is cytotoxic to PANC-1, AsPC-1, and SW1990 pancreatic cancer cells (IC50s = 20.54-26.8 μM).2 It reduces the oxygen consumption rate (OCR) and induces apoptosis in SW1990 cells. Aspulvinone O (2.5 and 5 mg kg) reduces tumor growth in an SW1990 mouse xenograft model. |1. Zhang, P., Li, X.-M., Wang, J.-N., et al. New butenolide derivatives from the marine-derived fungus Paecilomyces variotii with DPPH radical scavenging activity. Phytochem. Lett. 11, 85-88 (2015).|2. Sun, W., Luan, S., Qi, C., et al. Aspulvinone O, a natural inhibitor of GOT1 suppresses pancreatic ductal adenocarcinoma cells growth by interfering glutamine metabolism. Cell Commun. Signal. 17(1), 111 (2019).

MET PDGFRA-IN-2（化合物8h）是一种针对MET和PDGFRA蛋白的抑制剂，具有诱导细胞凋亡（apoptosis）的功能。该化合物能有效抑制多种MET表达细胞系的增殖，包括AsPc-1、EBC-1、MKN-45、Mia-Paca-2、HT-29和K562细胞，其IC50分别为9.7、6.1、12.0、11.5、8.6和34.4μM。

LP-184 (Compound 6), referred to as an acylfulvene analog, demonstrates the ability to inhibit tumor growth with noteworthy anti-cancer efficacy observed across multiple cell lines, including ovarian, colon, prostate, and pancreatic.