fibrosarcoma

2-NP 是选择性的STAT1转录增强剂。它能够增强 IFN-γ 的功能，提高对人乳腺癌和纤维肉瘤细胞增殖的抑制能力。

p-Hydroxy-5,6-dehydrokawain (4'-Hydroxydehydrokawain) 是一种分离自 Kawain 的天然产物。

Tesaglitazar 是一种有效且具有选择性的过氧化物 PPAR α γ受体双重激动剂，对 PPARγ的亲和力比 PPARα更有效，对大鼠PPARα和人PPARα的EC50分别为13.4 μM 和3.6 μM,对大鼠PPARγ和人类 PPARγ的EC50都是0.2 μM。Tesaglitazar 诱导大鼠皮下组织间质间充质细胞DNA 合成和纤维肉瘤形成。

Chlorin E6 (CE6) 是一种第二代光敏剂，在与辐照结合使用时具有抗肿瘤活性。在植入性纤维肉瘤的小鼠模型中，Chlorin E6（2.5-10 毫克 千克，静脉注射，50-200 焦耳 平方厘米的辐照）在不同程度的辐照后会导致肿瘤完全消失。在一项针对支气管源性早期浅表鳞状细胞癌患者的 I 期临床研究中，对包括 Chlorin E6 在内的制剂进行了测试，结果良好（40 毫克 平方米，静脉注射，100 焦耳 平方厘米的激光辐照）。在一项针对早期肺癌患者的二期临床试验中，同样的给药模式使 82.9% 的患者获得了完全应答。Chlorin E6 已被研究为一种纳米技术给药工具。

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.

Crebanine 是来自于韦诺萨千金藤的一种生物碱，通过抑制 MAPKs 和 Akt 信号通路表现出抗炎活性，还具有抗心律失常的作用。它可诱导人类癌细胞的 G1阻滞和凋亡。

Cytostatin (sodium salt) is a natural antitumor inhibitor of cell adhesion to extracellular matrix, blocking adhesion of B16 melanoma cells to laminin and collagen type IV in vitro (IC50s = 1.3 and 1.4 μg/ml, respectively) and B16 cells metastatic activity in mice. It induces apoptosis of FS3 mouse fibrosarcoma cells (IC50 = 3.1 μg/ml). Cytostatin (sodium salt) potently and selectively inhibits protein phosphatase 2A (PP2A; IC50 = 29 nM against the catalytic subunit), while having no effect against PP1, PP2B, or PP5.

PRLX-93936 is an analog of erastin that has antitumor activity. It inhibits the hypoxia-inducible factor 1 (HIF-1) signaling pathway under hypoxic conditions (IC50 = 0.09 μM in a cell-based reporter assay). PRLX-93936 (1 μM) also inhibits hypoxia-induced increases in HIF-1α expression in ME-180 cervical cancer cells. It inhibits the growth of HT-1080 fibrosarcoma, OVCAR-5 ovarian cancer, BJELR tumorigenic primary fibroblast, and PANC-1 pancreatic cancer cells with IC50 values of less than 100 nM. PRLX-93936 inhibits tumor growth in PANC-1 and HT-1080 xenograft models when administered at a dose of 50 mg/kg and induces tumor regression when administered at a dose of 100 mg/kg.

Heliquinomycin is a bacterial metabolite originally isolated fromStreptomycesthat has diverse biological activities.1It is active against a variety of Gram-positive bacteria, including strains ofB. anthracis, B. subtilis, and methicillin-sensitive or -resistantS. aureus(MICs = <0.05-0.39 μg/ml). Heliquinomycin inhibits the activity of DNA helicase with a Kivalue of 6.8 μM. It reduces the growth of L1210 leukemia, B16 melanoma, and FS-3 fibrosarcoma cells (IC50s = 0.97, 0.89, and 0.83 μg/ml, respectively). 1.Chino, M., Nishikawa, K., Umekita, M., et al.Heliquinomycin, a new inhibitor of DNA helicase, produced by Streptomyces sp. MJ929-SF2 I. Taxonomy, production, isolation, physico-chemical properties and biological activitiesJ. Antibiot. (Tokyo)49(8)752-757(1996)

Cytostatin is a natural antitumor inhibitor of cell adhesion to extracellular matrix, blocking adhesion of B16 melanoma cells to laminin and collagen type IV in vitro (IC50s = 1.3 and 1.4 μg ml, respectively) and B16 cells metastatic activity in mice. It induces apoptosis of FS3 mouse fibrosarcoma cells (IC50 = 3.1 μg ml). Cytostatin potently and selectively inhibits protein phosphatase 2A (PP2A; IC50 = 29 nM against the catalytic subunit), while having no effect against PP1, PP2B, or PP5.

Bisucaberin is a siderophore and bacterial metabolite that has been found inA. haloplanktisand has anticancer activity.1,2It inhibits the growth of L1210 and 1MC carcinoma cells (IC50s = 9.7 and 12.7 μM, respectively) and sensitizes fibrosarcoma 1023 cells to macrophage-mediated cytolysis. 1.Hou, Z., Raymond, K.N., O’Sullivan, B., et al.A preorganized siderophore: Thermodynamic and structural characterization of alcaligin and bisucaberin, microbial macrocyclic dihydroxamate chelating agentsInorg. Chem.37(26)6630-6637(1998) 2.Kameyama, T., Takahashi, A., Kurasawa, S., et al.Bisucaberin, a new siderophore, sensitizing tumor cells to macrophage-mediated cytolysis. I. Taxonomy of the producing organism, isolation and biological propertiesJ. Antibiot. (Tokyo)40(12)1664-1670(1987)

Belvarafenib TFA (HM95573 TFA) 是一种有效的、广泛的迅速加速纤维肉瘤激酶(RAF)的抑制剂，能够作用于 B-RAF (IC50: 56 nM)、B-RAFv600E (IC50: 7 nM) 和 C-RAF (IC50: 5 nM)。

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.

EGFR peptide (myristoylated) 是一种合成的肽类PKC抑制剂，其IC50值为5µM，与EGFR内部区域的氨基酸序列相对应。当浓度为1µM时，可以逆转紫外线-2237M (UV-2237M-ADRR) 成纤维细胞瘤细胞对多柔比星的抗药性。

GPX4 24是(1S,3R)-RSL3的衍生物，具有抑制谷胱甘肽过氧化物酶4（GPX4）的作用。它能够在浓度依赖的方式中与4T1小鼠乳腺癌细胞中的GPX4形成共价结合。在GPX4依赖的HT-1080成纤维细胞中，GPX4 24诱导铁死亡（EC50 = 0.16 µM）。当以200 mg/kg剂量给予小鼠时，它能够增加小鼠肾脏和血浆中丙二醛（MDA）的水平。

icFSP1是一种抑制剂，针对的是铁死亡抑制蛋白1（FSP1）。在2.5 µM的浓度下使用时，能够引发FSP1在细胞中的凝聚和相分离，但在无细胞测试中并不抑制FSP1的酶活性（IC50 = > 30 µM）。icFSP1以浓度依赖的方式诱导HT-1080纤维肉瘤细胞的铁死亡。在体内，icFSP1（50 mg kg）通过使用人类过表达FSP1，Gpx4- -Fsp1- -的B16 F10细胞，在B16 F10鼠黑色素瘤模型中减少肿瘤体积和重量。

GIC-20 是一种细胞凋亡 (apoptosis) 和铁死亡 (ferroptosis) 的双重诱导剂，对纤维肉瘤具有抗肿瘤活性。

Ferroptosis-IN-11(compound 43)作为一种铁死亡 (ferroptosis) 抑制剂,能够有效抑制Erastin诱导的HT-1080人纤维细胞铁死亡,其EC50为36 nM.此化合物对于心血管疾病和神经退行性疾病的研究具有潜在应用价值.

9,10-Dimethoxycanthin-6-one shows cytotoxic activity against a HT-1080 human fibrosarcoma cell line( IC50 = 5.0 microM).

Calyxin B exhibits potent activity against human HT-1080 fibrosarcoma cells with an ED50 value of 0.69 microM. A methylated product of calyxin A and an epimeric mixture of Calyxin B, showed greatly reduced activity suggesting that phenolic hydroxyl groups

Dihydroniloticin shows cytotoxic activity against a HT-1080 human fibrosarcoma cell line( IC50 = 8.2 microM).

Nagilactone C and phyllanthoside are novel protein synthesis inhibitors, they are specific for the eukaryotic translation apparatus, function in vivo and in vitro, and interfere with translation elongation. Nagilactone C shows high insecticidal activity against second-instar nymphs of Eocanthecona furcellata. Nagilactone C possesses potent antiproliferative activity against human fibrosarcoma and murine colon carcinoma tumor cell lines exhibiting ED50 values of 2.3 and 1.2 microg ml, respectively.