phosphoinositide 3-kinase a

TGX-115是一种细胞渗透性和有效的PI 3-K 异构体p110β p110δ抑制剂(对p110β IC50值为 0.13 μM, 对p110δ值为0.63 μM），是一种调节血小板粘附过程的酶，可抑制磷酸肌苷（PI）3-激酶，可用来治疗冠状动脉闭塞、中风、急性冠状动脉综合征、急性心肌梗塞、血管再狭窄、动脉硬化和不稳定心绞痛等心血管疾病 。

(2S,3R,4S)-4-Hydroxyisoleucine (Hydroxyisoleucine) 是分离自胡芦巴中的一种可口服的有效成分，具有抗糖尿病、抗糖尿病肾病的作用。

Solenopsin HCl 是一种可从火蚁中提取的生物碱，是磷脂酰肌醇-3-激酶信号传导和血管生成的抑制剂，剂量依赖性抑制心血管功能，可用于研究心血管疾病。

Glaucocalyxin A (Leukamenin F) 是来自日本黑纹病菌的一种对映型月桂基二萜，具有抗肿瘤作用。它通过调节PI3K Akt 信号通路抑制 GLI1 的核易位，诱导骨肉瘤凋亡。

Copanlisib (BAY 80-6946) 是一种选择性的和 ATP 竞争性的泛 I 类PI3K 抑制剂，具有抗肿瘤活性，对PI3Kα，PI3Kδ，PI3Kβ和PI3Kγ的IC50分别为 0.5 nM、0.7 nM、3.7 nM 和 6.4 nM。

A66 是高效的、特异性的、选择性 p110α 抑制剂，其 IC50=32 nM。

GDC-0326是一种有效，选择性的 PI3Kα抑制剂，Ki=0.2 nM。

BX-912 是一种直接的，选择性的，ATP 竞争性的PDK1抑制剂，IC50值为 26 nM。它阻断肿瘤细胞 PDK1 Akt 信号转导，抑制多种肿瘤细胞株的锚定依赖性生长或诱导凋亡。

PI3Kδ-IN-9 is a selective PI3Kδ inhibitor with an IC 50 value of 3.8 nM.

PF-376304 is a nonspecific PI3K inhibitor under development for anti-inflammatory indications. Phosphoinositide 3-kinase (PI3K) is an enzyme fundamental to the regulation of various metabolic processes.

WR23 is a piperidinylquinoxaline derivative and a phosphoinositide 3-kinase α (PI3Kα) inhibitor.

FD223 is a potent and selective phosphoinositide 3-kinase delta (PI3Kδ) inhibitor. FD223 displays high potency (IC50=1 nM) and good selectivity over other isoforms (IC50s of 51 nM, 29 nM and 37 nM, respectively for α, β and γ). FD223 exhibits efficient inhibition of the proliferation of acute myeloid leukemia (AML) cell lines by suppressing p-AKT Ser473 thus causing G1 phase arrest during the cell cycle. FD223 has potential for the research of leukemia such as AML[1].

Phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) act synergistically in promoting cancer. Wortmannin is a potent inhibitor of PI3K enzymes, while rapamycin blocks mTOR Complex 1 TORC1. Wortmannin-rapamycin conjugate consists of analogs of 17-hydroxy wortmannin and rapamycin conjugated via a prodrug linker. Hydrolysis of the prodrug linker in vivo releases the inhibitors. The wortmannin-rapamycin conjugate inhibits the growth of HT-29 colon tumors and A498 renal tumors in mice better than rapamycin alone. Also, the conjugate, when given in combination with the VEGF-blocker bevacizumab, produces substantial regression of larger A498 tumors. Finally, the wortmannin-rapamycin conjugate is tolerated better than an equivalent mixture of the inhibitors.

PI3Kγ inhibitor 5 is a potent inhibitor of phosphoinositide 3-kinase γ (PI3Kγ), exhibiting an exceptional IC50 value of 34 nM.

Copanlisib Dihydrochloride is a novel phosphoinositide 3-kinase (pi3k) inhibitor, inhibiting the activation of the pi3k signaling pathway, resulting in inhibition of tumor cell growth and survival in susceptible tumor cell populations

Duvelisib, also known as IPI-145 and INK-1197, is an orally bioavailable, highly selective and potent small molecule inhibitor of the delta and gamma isoforms of phosphoinositide-3 kinase (PI3K) with potential immunomodulating and antineoplastic activities. Upon administration, PI3K delta gamma inhibitor IPI 145 prevents the activation of the PI3K delta gamma-mediated signaling pathways which may lead to a reduction in cellular proliferation in PI3K delta gamma-expressing tumor cells. Unlike other isoforms of PI3K, the delta and gamma isoforms are overexpressed primarily in hematologic malignancies and inflammatory and autoimmune diseases.

WAY-278705 是一种磷酸肌醇三激酶 (PI3 kinase) 调节剂。

PI3K-IN-10 is a potent inhibitor of pan-PI3K .

BMS-554417 is a novel inhibitor of IGF-IR, which inhibits IGF-IR and insulin receptor kinase activity and proliferation in vitro, and reduces tumor xenograft size in vivo. In a series of carcinoma cell lines, the IC50 for proliferation ranged from 120 nmol L (Colo205) to >8.5 micromol L (OV202). BMS-554417 treatment inhibited IGF-IR and insulin receptor signaling through extracellular signal-related kinase as well as the phosphoinositide 3-kinase Akt pathway, as evidenced by decreased Akt phosphorylation at Ser473. At doses that inhibited proliferation, the compound also caused a G0-G1 arrest and prevented nuclear accumulation of cyclin D1 in response to LR3 IGF-I. In Jurkat T-cell leukemia cells, this agent triggered apoptotic cell death via the mitochondrial pathway. BMS-554417 was orally bioavailable and significantly inhibited the growth of IGF1R-Sal tumor xenografts in vivo. BMS-554417 is a member of a novel class of IGF-IR insulin receptor inhibitors that have potential......

CD2019 is a retinoic acid receptor beta (rarbeta) agonist, overcoming inhibition of axonal outgrowth via phosphoinositide 3-kinase signalling in the injured adult spinal cord.

Hederacolchiside A1 (Raddeanoside R13) 是从白头翁中分离的一种有抗利什曼原虫和抗肿瘤增殖活性的天然产物。

BX-320 is an inhibitor of the serine/threonine kinase 3-phosphoinositide-dependent protein kinase 1 (PDK1; IC50= 30 nM).1It is selective for PDK1 over a panel of 10 additional kinases (IC50s = >820 nM for all). BX-320 inhibits Akt and p70S6K1 phosphorylation in PC3 cells (IC50s = 1-3 μM). It induces apoptosis in, and inhibits the growth of, MDA-MB-468 breast cancer cells (IC50s = 0.5 and 0.6 μM, respectively), as well as inhibits cell growth in a panel of cancer cells (IC50s = 0.12-1.2 μM). BX-320 (200 mg/kg) inhibits the growth of lung tumors in a LOX melanoma mouse model of blood-borne metastasis. 1.Feldman, R.I., Wu, J.M., Polokoff, M.A., et al.Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1J. Biol. Chem.280(20)19867-19874(2005)

Olmutinib is a novel third-generation epidermal growth factor receptor (EGFR) mutation-specific tyrosine kinase inhibitor, used in the treatment of T790M mutation positive non-small cell lung cancer. Olmutinib covalently binds a cysteine residue near the kinase domain of mutant EGFRs to prevent phosphorylation of the receptor. EGFRs are frequently over-expressed in lung cancer and contribute to activation of the phosphoinositide 3-kinase and mitogen-activated protein kinase pathways which both promote cell survival and proliferation. By inhibiting EGFR activation, Olmutinib attenuates the activation of these tumor-promoting pathways. In the first phase I II clinical study of Osimertinib, 800 mg day was chosen as the dose for subsequent studies, and the dose-limiting toxicity and maximum tolerated dose was not reached. Olmutinib received breakthrough therapy designation in the United States in December 2015 and was approved for use in Korea in May 2016.

Phosphatidylinositol 4,5-bisphosphate（L-alpha-Phosphatidylinositol-4,5-bisphosphate）为细胞膜磷脂成分，主要作为磷脂酶C（PLC）与磷酸肌醇3-激酶（PI3K）的底物，充当重要信使。