"目录号: HY-15245

PI3K/Akt/mTOR-

GSK2636771 是一种有效的，选择性的，可口服的PI3Kβ抑制剂，无 PTEN 的细胞株对其敏感。

PI3K

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生物活性

Description

GSK2636771 is a potent, selective and orally bioavailablePI3Kβinhibitor, sensitive to PTEN null cell lines.

In Vitro

GSK2636771 treatment causes cell viability significantly more decreased in the control cells (p110β-reliant PTEN-deficient PC3 prostate and BT549 and HCC70 breast cancer cell lines) than in PTEN-mutant and PTEN wild-type EEC cells. Inhibition of p110β by GSK2636771 or AZD6482 leads to a marked decrease of AKT phosphorylation only in the control prostate and breast cancer cell lines, whereas only marginal effects on AKT activation are observed in EEC cells[1].

In Vivo

GSK2636771 is a p110β inhibitor, and the p110β primes cells for response to growth factor stimulation. While p110β inhibition suppresses cell and tumor growth, dual targeting of p110α/β enhances apoptosis and provides sustained tumor response in mice model[2].

Clinical Trial

NCT03131908

M.D. Anderson Cancer Center-National Cancer Institute (NCI)-National Institutes of Health (NIH)-Merck Sharp & Dohme Corp.-GlaxoSmithKline

Melanoma and Other Malignant Neoplasms of Skin-Metastatic Melanoma

July 17, 2017

Phase 1-Phase 2

NCT02215096

GlaxoSmithKline

Cancer

November 13, 2014

Phase 1

NCT01458067

GlaxoSmithKline

Cancer

November 10, 2011

Phase 1

NCT02615730

Yonsei University

Advanced Gastric Adenocarcinoma

February 2016

Phase 1-Phase 2

NCT02465060

National Cancer Institute (NCI)

Advanced Malignant Solid Neoplasm-Bladder Carcinoma-Breast Carcinoma-Cervical Carcinoma-Colon Carcinoma-Colorectal Carcinoma-Endometrial Carcinoma-Esophageal Carcinoma-Gastric Carcinoma-Glioma-Head and Neck Carcinoma-Kidney Carcinoma-Liver and Intrahepatic Bile Duct Carcinoma-Lung Carcinoma-Lymphoma-Malignant Uterine Neoplasm-Melanoma-Ovarian Carcinoma-Pancreatic Carcinoma-Plasma Cell Myeloma-Prostate Carcinoma-Rectal Carcinoma-Recurrent Bladder Carcinoma-Recurrent Breast Carcinoma-Recurrent Cer

August 12, 2015

Phase 2

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References

[1].Weigelt B, et al. PI3K pathway dependencies in endometrioid endometrial cancer cell lines. Clin Cancer Res. 2013, 19(13), 3533-3544.

[2].Hosford SR, et al. Combined inhibition of both p110α and p110β isoforms of phosphatidylinositol 3-kinase is required for sustained therapeutic effect in PTEN-deficient, ER+ breast cancer. Clin Cancer Res. 2016 Nov 30.