Novel Pi3k(小说 Pi3k)研究综述
Novel Pi3k 小说 Pi3k - In conclusion, our results show a novel PI3K-independent effect of buparlisib that may improve therapeutic efficacy and safety of daunorubicin by preventing its metabolism by AKR1C3. [1] CYH33 is a novel PI3Kα-selective inhibitor in phase I clinical trials (NCT03544905) and exhibits potent activity against breast cancer in preclinical settings. [2] CYH33 is a novel PI3Kα-selective inhibitor and displays promising efficacy against ESCC in preclinical settings, which is currently in phase I clinical trial for the treatment of ESCC. [3] As PI3Kα controls a key oncogenic signaling pathway, we evaluated whether RT or novel PI3Kαδ inhibitor or both could enhance the efficacy of antitumor effect of a PD-1 blockade in immune competent syngenic triple negative breast cancer (TNBC) model. [4] CONCLUSIONS Crystallography-based pharmacophores were successfully combined with QSAR analysis for the identification of novel PI3Kδ inhibitors. [5] Herein, we have discovered a series of novel PI3K and HDAC dual inhibitors in which the hydroxamic acid moiety as the zinc binding functional group was introduced to a quinazoline-based PI3K pharmacophore through an appropriate linker. [6] PBT-6, a novel PI3KC2γ inhibitor, decreased the cell growth of TNF-mediated synovial fibroblasts and LPS-mediated macrophages. [7] AS2541019 is a novel PI3Kδ selective inhibitor that prevents antibody production by inhibiting B cell immunity. [8] We have developed a synthesis of a novel PI3Kγ inhibitor containing a 1,2-dihydro-3H-pyrrolo[3,4-c]pyridin-3-one scaffold. [9] Herein, we synthesized a new series of substituted 2-(thiophen-2-yl)-1,3,5-triazine derivatives as novel PI3Kα/mTOR dual inhibitors for cancer therapy. [10] A summary of mechanisms underlying the adverse effects is not only significant for the development of novel PI3K/AKT/mTOR inhibitors but also beneficial for the optimal use of existing drugs. [11] Using specific protein interactome strategy by BirA proximity-dependent biotin identification, we demonstrated that FKBP4 is a novel PI3K-Akt-mTOR proximal interacting protein. [12] In our previous study, we rationally designed and synthesized DFX117(6-(5-(2,4-difluorophenylsulfonamido)-6-methoxypyridin-3-yl)-N-(2-morpholinoethyl) imidazo[1,2-a]pyridine-3-carboxamide) as a novel PI3Kα selective inhibitor. [13]总之，我们的结果显示了 buparlisib 的一种新的 PI3K 非依赖性作用，可以通过 AKR1C3 阻止其代谢来提高柔红霉素的治疗效果和安全性。 [1] CYH33 是 I 期临床试验 (NCT03544905) 中的一种新型 PI3Kα 选择性抑制剂，在临床前环境中表现出对乳腺癌的有效活性。 [2] CYH33 是一种新型 PI3Kα 选择性抑制剂，在临床前环境中显示出对 ESCC 的良好疗效，目前正处于治疗 ESCC 的 I 期临床试验中。 [3] 由于 PI3Kα 控制一个关键的致癌信号通路，我们评估了 RT 或新型 PI3Kαδ 抑制剂或两者是否可以增强 PD-1 阻断剂在免疫活性同基因三阴性乳腺癌 (TNBC) 模型中的抗肿瘤效果。 [4] 结论 基于晶体学的药效团成功地与 QSAR 分析相结合，用于鉴定新型 PI3Kδ 抑制剂。 [5] 在此，我们发现了一系列新型 PI3K 和 HDAC 双重抑制剂，其中异羟肟酸部分作为锌结合官能团通过适当的接头引入基于喹唑啉的 PI3K 药效团。 [6] PBT-6 是一种新型 PI3KC2γ 抑制剂，可降低 TNF 介导的滑膜成纤维细胞和 LPS 介导的巨噬细胞的细胞生长。 [7] AS2541019 是一种新型 PI3Kδ 选择性抑制剂，通过抑制 B 细胞免疫来阻止抗体产生。 [8] 我们开发了一种新型 PI3Kγ 抑制剂的合成方法，该抑制剂含有 1,2-dihydro-3H-pyrrolo[3,4-c]pyridin-3-one 支架。 [9] 在此，我们合成了一系列新的取代的 2-(thiophen-2-yl)-1,3,5-triazine 衍生物，作为用于癌症治疗的新型 PI3Kα/mTOR 双抑制剂。 [10] 总结不良反应的机制不仅对开发新型 PI3K/AKT/mTOR 抑制剂具有重要意义，而且有利于现有药物的优化使用。 [11] 通过 BirA 邻近依赖性生物素鉴定使用特定的蛋白质相互作用组策略，我们证明 FKBP4 是一种新的 PI3K-Akt-mTOR 近端相互作用蛋白。 [12] 在我们之前的研究中，我们合理设计并合成了 DFX117(6-(5-(2,4-difluorophenylsulfonamido)-6-methoxypyridin-3-yl)-N-(2-morpholinoethyl)imidzo[1,2-a]pyridine -3-carboxamide) 作为一种新型 PI3Kα 选择性抑制剂。 [13]
novel pi3k inhibitor 新型 Pi3k 抑制剂
Taken together, our findings establish B591, a novel PI3K inhibitor, as a strong candidate for clinical evaluation as a CSCs targeting agent. [1] The search for novel PI3K inhibitors has been at the forefront of academic and industrial medicinal chemistry with over 600 medicinal chemistry-based publications and patents appearing to date, leading to 38 clinical candidates and the launch of two drugs, idelalisib in 2014 and copanlisib in 2017. [2] Furthermore, novel PI3K inhibitors, such as idelalisib and copanlisib, have shown impressive clinical activity in several indolent lymphomas including marginal zone lymphoma (MZL). [3] Recently, lipomas associated with PIK3CA-related overgrowth syndrome were successfully treated with the novel PI3K inhibitor alpelisib. [4] In this context, after promising preclinical data on the novel PI3K inhibitor BYL719, the NCT01735968 trial in GIST patients who had previously failed treatment with imatinib and sunitinib started. [5]总之，我们的研究结果确立了 B591（一种新型 PI3K 抑制剂）作为 CSCs 靶向剂临床评估的有力候选者。 [1] 寻找新的 PI3K 抑制剂一直处于学术和工业药物化学的前沿，迄今为止出现了 600 多篇基于药物化学的出版物和专利，导致 38 种临床候选药物和两种药物的推出，2014 年的 idelalisib 和 2017 年的 copanlisib . [2] 此外，新的 PI3K 抑制剂，如 idelalisib 和 copanlisib，在包括边缘区淋巴瘤 (MZL) 在内的几种惰性淋巴瘤中显示出令人印象深刻的临床活性。 [3] 最近，与 PIK3CA 相关的过度生长综合征相关的脂肪瘤被新型 PI3K 抑制剂 alpelisib 成功治疗。 [4] 在这种情况下，在新型 PI3K 抑制剂 BYL719 的临床前数据令人鼓舞后，针对先前使用伊马替尼和舒尼替尼治疗失败的 GIST 患者的 NCT01735968 试验开始了。 [5]