生物活性

• 描述The PI3K/protein kinase B (AKT) pathway is commonly activated in several tumor types. Selective targeting of p110β could result in successful pathway inhibition while avoiding the on- and off-target effects of pan-PI3K inhibitors. GSK2636771 is a potent, orally bioavailable, adenosine triphosphate-competitive, selective inhibitor of PI3Kβ with IC₅₀s of 3.5 nM, 20.49 nM, 40.53 nM for p110α p110β and p110γ, respectively^[3]. In a vivo study, female nude mice with tumor xenografts were treated with vehicle or GSK2636771 at 1, 3, 10, or 30 mg/kg by oral gavage for 21 days and GSK2636771 resulted in tumor growth inhibition. In a cell study, C4-2B cells and its MDV3100-resistant subline was pretreated with GSK2636771 range from 1-100μM in 30mins. The result showed that treatment with GSK2636771 significantly increased G0/G1 population accompanied with a large reduction of S-phase cells not only in C4-2B cells but also in C4-2B/MDV-R cells, although the extent of G1/G0 phase arrest in MDV-R cells was less than that in the parental C4-2B cells^[4].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02951091	-	-	Recruiting	June 2020	Korea, Republic of ... more >> Severance Hospital, Yonsei University Health System, Yonsei Cancer Center Recruiting Seoul, Korea, Republic of, 120-752 Contact: Hyosong Kim, M.D    82-2-2228-8124    hyosong77@yuhs.ac Collapse <<
  NCT02465060	Advanced Malignant Solid Neopl... more >>asm 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 Cervical Carcinoma Recurrent Colon Carcinoma Recurrent Colorectal Carcinoma Recurrent Esophageal Carcinoma Recurrent Gastric Carcinoma Recurrent Glioma Recurrent Head and Neck Carcinoma Recurrent Liver Carcinoma Recurrent Lung Carcinoma Recurrent Lymphoma Recurrent Malignant Solid Neoplasm Recurrent Melanoma Recurrent Ovarian Carcinoma Recurrent Pancreatic Carcinoma Recurrent Plasma Cell Myeloma Recurrent Prostate Carcinoma Recurrent Rectal Carcinoma Recurrent Skin Carcinoma Recurrent Thyroid Gland Carcinoma Recurrent Uterine Corpus Carcinoma Refractory Lymphoma Refractory Malignant Solid Neoplasm Refractory Plasma Cell Myeloma Skin Carcinoma Thyroid Gland Carcinoma Uterine Corpus Cancer Collapse <<	Phase 2	Recruiting	-	-
  NCT02615730	Advanced Gastric Adenocarcinom... more >>a Collapse <<	Phase 1 Phase 2	Recruiting	December 2019	Korea, Republic of ... more >> Severance Hospital, Yonsei University Health System, Yonsei Cancer Center Recruiting Seoul, Korea, Republic of, 120-752 Contact: Minkju Jung, M.D    82-2-2228-8128    minkjung@yuhs.ac Collapse <<

• 更多
• 参考文献

• [1] Leroy C, Ramos P, et al. Activation of IGF1R/p110β/AKT/mTOR confers resistance to α-specific PI3K inhibition. Breast Cancer Res. 2016 Apr 5;18(1):41.

  [2] Weigelt B, Warne PH, et al. PI3K pathway dependencies in endometrioid endometrial cancer cell lines. Clin Cancer Res. 2013 Jul 1;19(13):3533-44.

  [3] Mateo J, Ganji G, Lemech C, Burris HA, Han SW, Swales K, Decordova S, DeYoung MP, Smith DA, Kalyana-Sundaram S, Wu J, Motwani M, Kumar R, Tolson JM, Rha SY, Chung HC, Eder JP, Sharma S, Bang YJ, Infante JR, Yan L, de Bono JS, Arkenau HT. A First-Time-in-Human Study of GSK2636771, a Phosphoinositide 3 Kinase Beta-Selective Inhibitor, in Patients with Advanced Solid Tumors. Clin Cancer Res. 2017 Oct 1;23(19):5981-5992. doi: 10.1158/1078-0432.CCR-17-0725. Epub 2017 Jun 23. PMID: 28645941.

  [4] He C, Duan S, Dong L, Wang Y, Hu Q, Liu C, Forrest ML, Holzbeierlein JM, Han S, Li B. Characterization of a novel p110β-specific inhibitor BL140 that overcomes MDV3100-resistance in castration-resistant prostate cancer cells. Prostate. 2017 Aug;77(11):1187-1198. doi: 10.1002/pros.23377. Epub 2017 Jun 20. PMID: 28631436; PMCID: PMC5527967.