A Series of Enthalpically Optimized Docetaxel Analogues Exhibiting Enhanced Antitumor Activity and Water Solubility

Ma, Yuntao; Yang, Yanting; Cai, Pei; Sun, Deyang; Sánchez‐Murcia, Pedro A.; Zhang, Xiaoying; Jia, Wen‐Qiang; Lei, Lei; Guo, Mengye; Gago, Federico; Wang, Hongbo; Fang, Wei‐Shuo

doi:10.1021/acs.jnatprod.7b00857

Cited by 39 publications

(28 citation statements)

References 42 publications

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“…B16-F10 tumors were established by injecting 1 × 10 5 cells mixed with matrigel into the dorsal area of male mice [18][19][20]. On 2 rd day, the mice bearing tumors were randomly divided into three groups (12/each group).…”

Section: In Vivo Tumor Isograft Model and Dosing Regimenmentioning

confidence: 99%

PCC0208025 (BMS202), a small molecule inhibitor of PD-L1, produces an antitumor effect in B16-F10 melanoma-bearing mice

et al. 2020

PLoS ONE

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The increased PD-L1 expression induces poorer prognosis in melanoma. The small molecule inhibitors of PD-1/PD-L1 pathways have been an encouraging drug development strategy because of good affinity and oral bioavailability without immunogenicity and immunotoxicities of PD-1/PD-L1 antibodies. In this study, we studied the effects of PCC0208025 (BMS202), a small molecule inhibitor of PD-L1, on PD-1/PD-L1 binding and the cytokines secretion in human CD3 + cells in vitro. We also investigated the antitumor and immunomodulatory activity of PCC0208025 and the pharmacokinetics properties in B16-F10 melanoma-bearing mice. The results showed that PCC0208025 inhibited the PD-1/PD-L1 proteins binding, and rescued PD-L1-mediated inhibition of IFN-γ production in human CD3 + T cells in vitro. Furthermore, in B16-F10 melanoma-bearing mice, PCC0208025 presented the antitumor effects, enhanced IFN-γ levels in plasma, increased the frequency of CD3 + CD8 + T and CD8 + IFN-γ + T and the ratios of CD8 + /Treg, and deceased the CD4 + CD25 + CD127 low/− (Treg) number in tumor. Pharmacokinetics study found that PCC0208025 was absorbed and distributed into the tumors with much higher concentrations than those of the blockade against PD-1/PD-L1 binding. Our work suggests that PCC0208025 exhibited anti-tumor effects through inhibiting Treg expansion and increasing cytotoxic activity of tumor-infiltrating CD8 + T cells by the blockade of PD-1/PD-L1 binding, which may provide the pharmacological basis to develop small molecule inhibitors of PD-1/PD-L1 binding for PCC0208025 as a lead compound.

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Section: In Vivo Tumor Isograft Model and Dosing Regimenmentioning

confidence: 99%

PCC0208025 (BMS202), a small molecule inhibitor of PD-L1, produces an antitumor effect in B16-F10 melanoma-bearing mice

et al. 2020

PLoS ONE

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“…Athymic nude mice (BALB/c-nu males, 6–8 weeks old, 18–20 g) were purchased from HFK Bioscience Co. (Beijing, People’s Republic of China) and housed at a temperature of 23.1°C with a 12-hour light–dark cycle with free access to food and water. A human esophageal cancer EC109 tumor from a donor mouse was cut into small pieces with surgical scissors and implanted subcutaneously in the flank of nude mice with a gauge trocar 21. When the tumor had grown to approximately 100 mm 3 in volume, the 18 nude mice were divided into three groups with almost equal mean tumor volume (six mice per group) and weighed.…”

Section: Methodsmentioning

confidence: 99%

<p>Cryptotanshinone inhibits esophageal squamous-cell carcinoma in vitro and in vivo through the suppression of STAT3 activation</p>

Yu-bin

Liu

Xue

et al. 2019

OTT

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PurposeEsophageal squamous-cell carcinoma (ESCC) is the most common subtype of esophageal cancer, with a poor clinical outcome. Cryptotanshinone (CTS) is the main bioactive compound from the root of Salvia miltiorrhiza Bunge. Our study aimed to investigate the anti-cancer effects and molecular mechanisms of CTS on ESCC.Materials and methodsWe investigated the anti-tumor activity of CTS on ESCC in vitro and in vivo. Activation of the STAT3 signaling pathway was evaluated in ESCC and HEK-Blue™ IL-6 cells. Cell viability was assessed by the MTT assay. Apoptosis and cell cycle arrest were assessed using flow cytometry. Cell migration was detected by a scratch wound assay.ResultsCTS inhibited STAT3 expression and IL-6-mediated STAT3 activation in esophageal cancer cells. Subsequently, CTS dose-dependently inhibited the proliferation of esophageal cancer cells via induction of cell apoptosis. Furthermore, CTS suppressed the migration of esophageal cancer cells. In vivo, CTS inhibited tumor growth of EC109 cell in xenograft mice without any obvious effect on body weight.ConclusionOur results indicated that STAT3 inhibition may be a therapeutic target for esophageal cancer. CTS could provide a potential approach for esophageal cancer therapy by influencing the janus kinase-2/STAT3 signaling pathway.

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“…Finally, 20 μL of MTT was added and the cells were incubated for 4 h. The MTT-formazan that formed by metabolically viable cells was dissolved in 100 μL of DMSO for 10 min. The absorbance was then measured at 570 nm with a microplate reader, in which the cell survival rates were calculated and the IC 50 was calculated following our previous method [26,27].…”

Section: Methodsmentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of Novel Nitrogen Heterocycle-Containing Ursolic Acid Analogs as Antitumor Agents

et al. 2019

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Nineteen ursolic acid analogues were designed, synthesized, and evaluated for their antiproliferative activity against the Hela and MKN45 cell lines. Some compounds containing a piperazine moiety displayed moderate to high levels of antitumor activities against the tested cancer cell lines. The most potent compound shares the IC50 value of 2.1 µM and 2.6 µM for the Hela and MKN45 cell lines, respectively. Further mechanism studies and in vivo antitumor studies have shown that it decreased the apoptosis regulator (BCL2/BAX) ratio, disrupted mitochondrial potential and induced apoptosis, and suppressed the growth of Hela xenografts in nude mice.

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A Series of Enthalpically Optimized Docetaxel Analogues Exhibiting Enhanced Antitumor Activity and Water Solubility

Cited by 39 publications

References 42 publications

PCC0208025 (BMS202), a small molecule inhibitor of PD-L1, produces an antitumor effect in B16-F10 melanoma-bearing mice

PCC0208025 (BMS202), a small molecule inhibitor of PD-L1, produces an antitumor effect in B16-F10 melanoma-bearing mice

<p>Cryptotanshinone inhibits esophageal squamous-cell carcinoma in vitro and in vivo through the suppression of STAT3 activation</p>

Design, Synthesis, and Biological Evaluation of Novel Nitrogen Heterocycle-Containing Ursolic Acid Analogs as Antitumor Agents

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