PI-3065

PI-3065 is a small molecule and selective inhibitor of p110δkinase with an Ki value of 1.5nM and IC50 value of 5nM [1].

PI-3065 has been reported to selectively inhibit p110δkinase with Ki values of 15nM, 110nM, 130nM and 940nM, IC50 values of 5nM, 91nM, 600nM and >10000nM for p110δ, p110α, p110β and p110γ, respectively. In addition, PI-3065 has been revealed to inhibit 4T1 tumour growth and metastasis. PI-3065 has also noted to prolong survival and reduce the incidence of macroscopic metastases and other disease-associated pathologies [1].

References:
[1] Ali K1, Soond DR2, Pi?eiro R1, Hagemann T3, Pearce W4, Lim EL5, Bouabe H5, Scudamore CL6, Hancox T7, Maecker H8, Friedman L8, Turner M5, Okkenhaug K9, Vanhaesebroeck B1. Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer. Nature. 2014 Jun 19;510(7505):407-11. doi: 10.1038/nature13444. Epub 2014 Jun 11.

Inhibition of p110delta PI3K prevents inflammatory response and restenosis after artery injury.[Pubmed:28851839]

Biosci Rep. 2017 Sep 27;37(5). pii: BSR20171112.

Inflammatory cells play key roles in restenosis upon vascular surgical procedures such as bypass grafts, angioplasty and stent deployment but the molecular mechanisms by which these cells affect restenosis remain unclear. The p110delta isoform of phosphoinositide 3-kinase (PI3K) is mainly expressed in white blood cells. Here, we have investigated whether p110delta PI3K is involved in the pathogenesis of restenosis in a mouse model of carotid injury, which mimics the damage following arterial grafts. We used mice in which p110delta kinase activity has been disabled by a knockin (KI) point mutation in its ATP-binding site (p110delta(D910A/D910A) PI3K mice). Wild-type (WT) and p110delta(D910A/D910A) mice were subjected to longitudinal carotid injury. At 14 and 30 days after carotid injury, mice with inactive p110delta showed strongly decreased infiltration of inflammatory cells (including T lymphocytes and macrophages) and vascular smooth muscle cells (VSMCs), compared with WT mice. Likewise, PI-3065, a p110delta-selective PI3K inhibitor, almost completely prevented restenosis after artery injury. Our data showed that p110delta PI3K plays a main role in promoting neointimal thickening and inflammatory processes during vascular stenosis, with its inhibition providing significant reduction in restenosis following carotid injury. p110delta-selective inhibitors, recently approved for the treatment of human B-cell malignancies, therefore, present a new therapeutic opportunity to prevent the restenosis upon artery injury.

Inactivation of PI(3)K p110delta breaks regulatory T-cell-mediated immune tolerance to cancer.[Pubmed:24919154]

Nature. 2014 Jun 19;510(7505):407-411.

Inhibitors against the p110delta isoform of phosphoinositide-3-OH kinase (PI(3)K) have shown remarkable therapeutic efficacy in some human leukaemias. As p110delta is primarily expressed in leukocytes, drugs against p110delta have not been considered for the treatment of solid tumours. Here we report that p110delta inactivation in mice protects against a broad range of cancers, including non-haematological solid tumours. We demonstrate that p110delta inactivation in regulatory T cells unleashes CD8(+) cytotoxic T cells and induces tumour regression. Thus, p110delta inhibitors can break tumour-induced immune tolerance and should be considered for wider use in oncology.

Targeting PI3K/Akt/mTOR Signaling in Cancer.[Pubmed:24782981]

Front Oncol. 2014 Apr 14;4:64.

The phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) signaling pathways are two pathways crucial to many aspects of cell growth and survival, in physiological as well as in pathological conditions (e.g., cancer). Indeed, they are so interconnected that, in a certain sense, they could be regarded as a single, unique pathway. In this paper, after a general overview of the biological significance and the main components of these pathways, we address the present status of the development of specific PI3K, Akt, and mTOR inhibitors, from already registered medicines to novel compounds that are just leaving the laboratory bench.

PI-3065 is a potent inhibitor of PI3K p110δ, with IC50 and Ki values of 5 nM and 1.5 nM, and exhibits less potent activity against p110α, p110β, p110γ with IC50s of 910, 600, >10000 nM.

PI-3065,955977-50-1,Natural Products,PI3K, buy PI-3065 , PI-3065 supplier , purchase PI-3065 , PI-3065 cost , PI-3065 manufacturer , order PI-3065 , high purity PI-3065