The oncogenic potential of phosphatidylinositol 3-kinase (PI3Kα) has made it an attractive target for anticancer drug design. In this work, we describe our efforts to optimize the lead PI3Kα inhibitor 2-hydroxy-1,2-diphenylethanone (benzoin). A series of 2-oxo-1,2-diphenylethyl benzoate analogs were identified as potential PI3Kα inhibitors. Docking studies confirmed that the aromatic interaction is mediating ligand/protein complex formation and identified Lys802 and Val851 as H-bonding key residues. Our biological data in human colon carcinoma HCT116 showed that the structure analogs inhibited cell proliferation and induced apoptosis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2015.06.011 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Epiberberine Improves Hyperglycemia and Ameliorates Insulin Sensitivity in Type 2 Diabetic Mice.
Nephrology (Carlton)
February 2025
Internal Medicine Department, Shenzhen Bao'an Authentic Tcm Therapy Hospital, Shenzhen, China.
Aim: Type 2 diabetes mellitus (T2DM) is a metabolic syndrome characterised by absolute or relative insufficiency of insulin secretion. The alkaloids from Rhizoma coptidis have potential hypoglycemic effects. Epiberberine (EPI), a protoberberine alkaloid extracted from Rhizome coptidis, has been found to regulate lipid metabolism.
View Article and Find Full Text PDFPreconditioning with acteoside ameliorates myocardial ischemia‑reperfusion injury by targeting HSP90AA1 and the PI3K/Akt signaling pathway.
Mol Med Rep
March 2025
Department of Cardiology, The First Affiliated Hospital to Jiamusi University, Jiamusi, Heilongjiang 154000, P.R. China.
The present study aimed to investigate the cardioprotective effects of acteoside (AC) on myocardial ischemia‑reperfusion injury (MIRI). To meet this aim, a network pharmacological analysis was conducted to search for key genes and signaling pathways associated with AC and MIRI. The infarct size of the rat heart was evaluated using 2,3,5‑triphenyltetrazolium chloride staining, and the serum levels of creatine kinase MB isoenzyme, cardiac troponin I, malondialdehyde and superoxide dismutase were subsequently detected in an experiment.
View Article and Find Full Text PDFEvaluation of co‑inhibition of ErbB family kinases and PI3K for HPV‑negative head and neck squamous cell carcinoma.
Oncol Rep
March 2025
Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
The ErbB/HER family of protein‑tyrosine kinases and PI3K represent crucial targets in the treatment of head and neck squamous cell carcinoma (HNSCC). A combination therapy of afatinib (ErbB inhibitor) and copanlisib (PI3K inhibitor), both Food and Drug Administration‑approved kinase inhibitors, can suppress the growth of human papillomavirus (HPV)‑positive HNSCC. The current study further evaluated the efficacy and clinical potential of this combination therapy for the treatment of HPV‑negative HNSCC and .
View Article and Find Full Text PDFElectroacupuncture improves cognitive impairment after subarachnoid hemorrhage in rats through the PI3K/AKT signaling pathway.
Acupunct Med
January 2025
Combination of Acupuncture and Medicine Innovation Research Center, Shaanxi University of Chinese Medicine, Xianyang, China.
Objective: Cognitive impairment (CI) is highly prevalent in subarachnoid hemorrhage (SAH) patients. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway plays a critical role in neuronal survival in a variety of central nervous system injuries. This study aimed to determine whether electroacupuncture (EA) at and LI20 ameliorates SAH-CI in a rat model and to examine whether it modulates the PI3K/AKT pathway by administering a PI3K inhibitor (LY294002) versus dimethyl sulfoxide (DMSO) vehicle.
View Article and Find Full Text PDFAlpelisib is a phosphatidylinositol 3-kinase inhibitor approved by the US Food and Drug Administration for the treatment of hormone receptor-positive metastatic breast cancer with (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α) mutation. In recent years a number of adverse effects have been observed to be associated with this therapy, the most notable of which is hyperglycemia. A literature search was conducted to include case studies, case series, systematic reviews, and meta-analyses within the last 10 years that evaluated patients with mutated hormone receptor-positive, human epidermal growth factor receptor 2 negative metastatic breast cancer.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!