Exploring target selectivity in designing and identifying PI3Kα ...
3 days ago · PI3Kα selective inhibition can decrease the TNBC by a significant level with minimal off-target effects. Novel compounds with high selectivity towards PI3Kα are crucial for treating TNBC. After ...
Structural insights into isoform-specific RAS-PI3Kα ... - Nature
Jan 9, 2025 · Mutations in RAS and PI3Kα are major drivers of human cancer. Their interaction plays a crucial role in activating PI3Kα and amplifying the PI3K-AKT-mTOR pathway. Disrupting RAS-PI3Kα ...
Phosphoinositide 3-kinase - Wikipedia
Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer.
Predicting breast cancer prognosis using PR and PIK3CA …
2 days ago · Inavolisib, known for its high in vitro PI3Kα inhibitory potency and selectivity, uniquely promotes the degradation of mutated PI3Kα proteins. This dual mechanism of action allows Inavolisib to provide durable and well-tolerated disease control for patients with PIK3CA mutations [ 33 ], a finding robustly supported by the phase III INAVO120 ...
PI3Kα药物靶点研发进展 - synapse.zhihuiya.com
Jul 18, 2023 · pi3kα是一种重要的脂质激酶，是癌症中最常发生突变的激酶之一。 由催化亚基p110α和调节亚基p85α共同组成异二聚体，与细胞生长和增殖密切相关，其功能获得性突变是肿瘤形成的驱动因素，因而成为治疗癌症的重要靶点。
罗氏的PI3Kα抑制剂3期取得成功，PI3Kα抑制剂进展如何？ - 知乎
Dec 8, 2023 · 不过好在诺华和罗氏的PI3Kα抑制剂都带来了好消息，诺华和罗氏都避开了靶向PI3Kδ用于血液瘤治疗的开发，而是开发靶向PI3Kα用于治疗PI3KCA突变的乳腺癌。 诺华的Alpelisib因去年获批治疗PIK3CA相关过度生长疾病谱系（PROS）成人和2岁及以上儿童患者的新适应症而使销售额得到上升。 今年12月5日， 罗氏的inavolisib联合疗法一线治疗乳腺癌的3期INAVO120研究达到了无进展生存期（PFS）的主要终点，与单独使用帕博西尼和 氟维司群 …
A small-molecule PI3Kα activator for cardioprotection and ...
May 24, 2023 · Here we report the discovery of UCL-TRO-1938 (referred to as 1938 hereon), a small-molecule activator of the PI3Kα isoform, a crucial effector of growth factor signalling. 1938 allosterically...
磷脂酰肌醇3-激酶(PI3K)信号通路 - 知乎 - 知乎专栏
磷脂酰肌醇3-激酶 (PI3Ks)蛋白家族参与细胞存活、生长、代谢和血糖稳态等多种细胞功能的调控。 PI3K激酶活性升高通常与多种癌症相关。 顾名思义，PI3Ks磷酸化磷脂酰肌醇PI（一种 膜磷脂）肌醇环的第3位碳原子。 PI在细胞膜组分中所占比例较小，比磷脂酰胆碱、磷脂酰乙醇胺和 磷脂酰丝氨酸 含量少, 但在脑细胞膜中，含量较为丰富，达磷脂总量的10%。 PI的肌醇环上有5个可被磷酸化的位点，多种激酶可磷酸化PI肌醇环上的第4及第5位点，因而通常在这两个位点之一或 …
PNAS | 科学家携手深度解析重要药靶——磷脂酰肌醇3激酶α的结构 …
Sep 18, 2022 · PI3Kα是一种重要的脂质激酶，由催化亚基p110α和调节亚基p85α共同组成异二聚体，与细胞生长和增殖密切相关，其功能获得性突变是肿瘤形成的驱动因素【1-2】，因而成为治疗癌症的重要靶点。
PI3K inhibitors: review and new strategies - RSC Publishing
Here we briefly review PI3Kα mutations, focus on PI3K drug repertoire and propose new, to-date unexplored PI3Kα therapeutic strategies. These include (1) an allosteric and orthosteric inhibitor combination and (2) taking advantage of allosteric rescue mutations to guide drug discovery.