mda-5

Polyinosinic-polycytidylic acid sodium (Poly(I:C) sodium) 是双链 RNA 的合成类似物，是TLR3和视黄酸诱导型基因 I 受体激动剂。它可以用作疫苗佐剂，直接触发癌细胞发生凋亡，还增强先天性和适应性免疫反应，并改变肿瘤的微环境。

Cinnamaldehyde (Cinnamic Aldehyde) 具有解热作用。 它是镇静剂。它抑制MDA-MB-435S 细胞的侵袭能力与下调miR-27a 的表达有关。它诱导活性氧的产生，发挥血管扩张和抗癌作用。 它似乎是一种有希望的候选药物，可作为与 5-氟尿嘧啶 (5-FU) 和奥沙利铂 (OXA) 这两种用于 CRC 治疗的化疗药物联合治疗的辅助剂。其作用的可能机制可能涉及药物代谢基因的调节。 它在抑制黑色素瘤的发生和发展方面具有一定的作用，其作用机制可能表现为抑制VEGF 和HIF-α的表达，从而使血管模拟和黑色素瘤细胞新生血管的形成，促进肿瘤的生长。

Aspirin (Acetylsalicylic Acid) 是一种 COX 抑制剂，抑制 COX1 和 COX2 (IC50=5 210 μg mL)，具有选择性、不可逆性和口服活性。Aspirin 也是一种组蛋白去乙酰化酶抑制剂，可上调细胞周期阻滞蛋白 p21。Aspirin 具有抗炎、解热镇痛、抗血小板聚集能多种活性。

Octyl gallate (Octyl 3,4,5-trihydroxybenzoate) 具有抗菌、抗氧化作用，有选择性和敏感性的荧光特性，广泛用作食品添加剂。它对 HSV-1，水泡性口炎病毒和脊髓灰质炎病毒有显著的抗病毒作用。

Nordihydroguaiaretic acid (NDGA) 属于天然产物，从极叉开拉瑞阿提取，是一种脂氧合酶 (5-LOX) 抑制剂 (IC50=8 μM)。Nordihydroguaiaretic acid 具有抗氧化和清除自由基的特性。

Peimisine (Ebeiensine) 非竞争性拮抗气管平滑肌 M 受体，抑制 Ach 引起的平滑肌收缩。它兴奋 β 受体和拮抗内钙释放，促进一氧化氮释放，可舒张气管平滑肌，有平喘作用。

PRGL493为高效、选择性的长链酰基辅酶a合成酶4 (ACSL4) 抑制剂，能在乳腺和前列腺细胞以及动物模型中抑制细胞增殖和肿瘤生长，主要应用于癌症研究。

PHGDH-IN-5 (Compound B12) 作为一种共价抑制剂，其IC50值为0.29 μM，特别针对PHGDH酶。在过表达PHGDH的癌细胞系中，PHGDH-IN-5 能有效抑制细胞增殖，并可在MDA-MB-468细胞中显著减少葡萄糖来源的丝氨酸产生。

(5E)-7-Oxozeaenol is a resorcylic acid lactone that has been found in the fungus MSX 63935 and has enzyme inhibitory and anticancer activities.1,2 It inhibits TGF-β-activated kinase 1 (TAK-1; IC50 = 1.3 μM).1 (5E)-7-Oxozeaenol inhibits proliferation of MCF-7, H460, SF-268, HT-29, and MDA-MB-435 human cancer cells with IC50 values of 4.9, 1.2, 5.6, 4.4, and 5.5 μM, respectively.2 |1. Fakhouri, L., El-Elimat, T., Hurst, D.P., et al. Isolation, semisynthesis, covalent docking and transforming growth factor beta-activated kinase 1 (TAK1)-inhibitory activities of (5Z)-7-oxozeaenol analogues. Bioorg. Med. Chem. 23(21), 6993-6999 (2015).|2. Ayers, S., Graf, T.N., Adcock, A.F., et al. Resorcylic acid lactones with cytotoxic and NF-κB inhibitory activities and their structure-activity relationships. J. Nat. Prod. 74(5), 1126-1131 (2011).

Anticanceragent 231 (化合物 P5) 作为一种酪氨酸蛋白激酶抑制剂，具有IC50值为3.95 μM。它通过针对EGFR-ERK1 2信号通路，能有效抑制三阴乳腺癌（TNBC）细胞的活力、增殖、迁移及癌症干性，显示出对TNBC治疗的重要潜力。

IRC-083927 HCl is novel and potent microtubule inhibitor with potential anticancer activity. IRC-083927 inhibits the tubulin polymerization by a binding to the colchicine site. IRC-083927 inhibits in vitro cell growth of human cancer cell lines in the low nanomolar range. More interesting, it remains highly active against cell lines resistant to microtubule-interacting agents (taxanes, Vinca alkaloids, or epothilones). Chronic oral treatment with IRC-083927 (5 mg kg) inhibits the growth of two human tumor xenografts in nude mice (C33-A, human cervical cancer and MDA-MB-231, human hormone-independent breast cancer). Together, the antitumor effects induced by IRC-083927 on tumor models resistant to tubulin agents support further investigations to fully evaluate its potential for the treatment of advanced cancers, particularly those resistant to current clinically available drugs.

BPR5K230 作为MER和AXL受体酪氨酸激酶的双重抑制剂，分别展示了4.1 nM和9.2 nM的IC50。该化合物还能抑制Ba F3-MER细胞的增殖，具体IC50达到5 nM。在小鼠体内，BPR5K230展现出优秀的药代动力学属性，并在4T1、MDA-MB-231、MC38和Hepa1-6小鼠模型中显示了抗炎及抗肿瘤活性。

SN-38-CM2 BS2是一种分裂酯酶，在体外5 min内转化为SN-38的转化率超过95%。SN-38-CM2通过诱导蛋白-蛋白相互作用 (PPI) 依赖的酯酶介导MDA-MB-231细胞死亡。

(E)-Ajoene is a disulfide that has been found inA. sativumand has diverse biological activities.1,2,3,4It is active against Gram-positive and Gram-negative bacteria (MICs = 10-250 and 150->500 μg/ml, respectively) and fungi (MICs = 15-50 μg/ml).1(E)-Ajoene inhibits proliferation of a variety of cancer cells, including MDA-MB-231 breast, HeLa cervical, and WHCO1 esophageal cancer cells (IC50s = 18.6, 61, and 39.2 μM, respectively).2It also inhibits human glutathione reductase andT. cruzitrypanothione reductase when used at a concentration of 200 μM.3(E)-Ajoene (25 mg/kg) is neuroprotective in a gerbil model of ischemia-reperfusion injury, reducing reactive astrocytosis and microgliosis in the hippocampal CA1 region.4 1.Yoshida, H., Iwata, N., Katsuzaki, H., et al.Antimicrobial activity of a compound isolated from an oil-macerated garlic extractBiosci. Biotechnol. Biochem.62(5)1014-1017(1998) 2.Kaschula, C.H., Hunter, R., Hassan, H.T., et al.Anti-proliferation activity of synthetic ajoene analogues on cancer cell-linesAnticancer Agents Med. Chem.11(3)260-266(2011) 3.Gallwitz, H., Bonse, S., Martinez-Cruz, A., et al.Ajoene is an inhibitor and subversive substrate of human glutathione reductase and Trypanosoma cruzi trypanothione reductase: Crystallographic, kinetic, and spectroscopic studiesJ. Med. Chem.42(3)364-372(1999) 4.Yoo, D.Y., Kim, W., Nam, S.M., et al.Neuroprotective effects of Z-ajoene, an organosulfur compound derived from oil-macerated garlic, in the gerbil hippocampal CA1 region after transient forebrain ischemiaFood Chem. Toxicol.721-7(2014)

TunR1 is an antibiotic and derivative of tunicamycin .1It is active againstB. subtilis(MIC = 0.3 μg ml) and increases the efficacy of the β-lactam antibiotics oxacillin , methicillin , and penicillin G againstB. subtiliswhen used at a concentration of 0.4 μg ml. TunR1 (5 μg ml) is cytotoxic to MDA-MB-231 breast cancer cells and non-cancerous CHO cells. Unlike tunicamycin, TunR1 does not inhibit glycosylation in a protein N-glycosylation assay. 1.Price, N.P., Hartman, T.M., Li, J., et al.Modified tunicamycins with reduced eukaryotic toxicity that enhance the antibacterial activity of β-lactamsJ. Antibiot. (Tokyo)70(11)1070-1077(2017)

USP1-IN-5 (compound 10) 作为USP1抑制剂展现出高效性（IC50<50 nM），并且对于MDA-MB-436细胞的生长具有显著的抑制作用，其IC50亦小于50 nM。

Coptisine (Coptisin) 是一种从黄连中分离到的生物碱，是非竞争性的IDO 抑制剂，Ki=为 5.8 μM，IC50=6.3 μM。

PKI-179 is a potent and orally active dual PI3K mTOR inhibitor, with IC50s of 8 nM, 24 nM, 74 nM, 77 nM, and 0.42 nM for PI3K-α, PI3K-β, PI3K-γ, PI3K-δ and mTOR, respectively. PKI-179 also exhibits activity over E545K and H1047R, with IC50s of 14 nM and 11 nM, respectively. PKI-179 shows anti-tumor activity in vivo[1][2]. PKI-179 inhibits the cell proliferation, with IC50s of 22 nM and 29 nM for MDA361 and PC3 cells, respectively[1].PKI-179 shows inhibitory activity against a panel of 361 other kinases, hERG and cytochrome P450 (CYP) isoforms at concentrations up to >30 μM, but does have activity for CYP2C8 (IC50=3 μM)[1]. PKI-179 (5-50 mg kg; p.o. once daily for 40 days) inhibits the tumor growth and is well tolerated in nude mice bearing MDA-361 human breast cancer tumors[1].PKI-179 (50 mg kg; p.o.) results in good inhibition of PI3K signaling in nude mice bearing MDA361 tumor xenografts[1].PKI-179 exhibits good oral bioavailability (98% in nude mouse, 46% in rat, 38% in monkey, and 61% in dog) and a high half-life (>60 min) [1]. [1]. Venkatesan AM, et, al. PKI-179: an orally efficacious dual phosphatidylinositol-3-kinase (PI3K) mammalian target of rapamycin (mTOR) inhibitor. Bioorg Med Chem Lett. 2010 Oct 1;20(19):5869-73.[2]. Rehan M. A structural insight into the inhibitory mechanism of an orally active PI3K mTOR dual inhibitor, PKI-179 using computational approaches. J Mol Graph Model. 2015 Nov;62:226-234.

YW3-56 is an inhibitor of protein arginine deiminase 2 (PAD2) and PAD4 (IC50s = 0.5-1 and 1-5 μM, respectively).1It inhibits the growth of U2OS osteosarcoma cells (IC50= ~2.5 μM) in a p53-dependent mannerviainduction of SESN2 and subsequent inhibition of mTORC1. YW3-56 (10 mg kg) reduces tumor growth in an S-180 murine sarcoma tumor model. It also inhibits tumor growth in the 1883 MDA-MB-231 breast cancer bone metastasis mouse xenograft model.2 1.Wang, Y., Li, P., Wang, S., et al.Anticancer peptidylarginine deiminase (PAD) inhibitors regulate the autophagy flux and the mammalian target of rapamycin complex 1 activityThe Journal of Biological Chemisty287(31)25941-25952(2012) 2.Wang, S., Chen, X.A., Hu, J., et al.ATF4 gene network mediates cellular response to the anticancer PAD inhibitor YW3-56 in triple-negative breast cancer cellsMol. Cancer Ther.14(4)877-888(2015)

CADD522 (MFCD00167693) 是 runt 相关转录因子-2 (RUNX2)-DNA 结合的抑制剂(IC50:10 nM)，具有抗肿瘤作用。

Antiproliferative agent-64 (Compound 76) 是一种抑制真核翻译起始因子 4E (eIF4E) 的化合物，可通过阻断mRNA的二级结构来抑制蛋白质翻译。它对c-Myc的5'非翻译区 (c-myc 5'UTR) 的抑制作用的EC50为1.2 nM，对编码微管蛋白的5'UTR (tub 5'UTR) 的抑制作用的EC50为40 nM。此外，Antiproliferative agent-64 对MDA-MB-231细胞增殖的抑制作用的EC50为7 nM。

5-Hydroxyflavone 是类黄酮配体，对 FaDU，MCF-7，U87，MDA-MB-435S，RPE-1 和 HEK293 细胞没有细胞毒性。

Pergolide mesylate salt(LY127809) 是一种有效的，具有口服活性的多巴胺 D1和 D2受体激动剂，是一种 Ergoline 衍生物，可用于帕金森氏病和高泌乳素血症的研究。

PAK4-IN-5 (Compound 12i) 作为一种高效的PAK4抑制剂，显示出对PAK4的极低IC50值，为7.68 nM，同时对PAK1的IC50值为1872.01 nM。该化合物通过多种相互作用有效地与PAK4结合，并能显著抑制MDA-MB-231细胞的磷酸化PAK4和LIMK1，从而抑制其增殖和迁移能力。此外，PAK4-IN-5能够引起细胞周期在G0 G1期的停滞，诱导细胞凋亡（Apoptosis）及活性氧的产生。其半致死剂量（LD50）在小鼠中为超过500 mg kg（口服）。