Results 61 to 70 of about 193,906 (268)

Discovery of Highly Isoform Selective Orally Bioavailable Phosphoinositide 3-Kinase (PI3K)-γ Inhibitors [PDF]

Journal of Medicinal Chemistry, 2018
In this paper, we describe the discovery and optimization of a new chemotype of isoform selective PI3Kγ inhibitors. Starting from an HTS hit, potency and physicochemical properties could be improved to give compounds such as 15, which is a potent and remarkably selective PI3Kγ inhibitor with ADME properties suitable for oral administration. Compound 15
Nils Pemberton, Mickael Mogemark, Susanne Arlbrandt, Peter Bold, Rhona J. Cox, Cristina Gardelli, Neil S. Holden, Kostas Karabelas, Johan Karlsson, Sarah Lever, Xueshan Li, Helena Lindmark, Monica Norberg, Matthew W. D. Perry, Jens Petersen, Sandra Rodrigo Blomqvist, Matthew Thomas, Christian Tyrchan, Annika Westin Eriksson, Pavol Zlatoidsky, Linda Öster   +20 more
openaire   +4 more sources

Transcriptional network analysis of PTEN‐protein‐deficient prostate tumors reveals robust stromal reprogramming and signs of senescent paracrine communication

Molecular Oncology, EarlyView.
Combining PTEN protein assessment and transcriptomic profiling of prostate tumors, we uncovered a network enriched in senescence and extracellular matrix (ECM) programs associated with PTEN loss and conserved in a mouse model. We show that PTEN‐deficient cells trigger paracrine remodeling of the surrounding stroma and this information could help ...
Ivana Rondon‐Lorefice, Jose I. Lopez, Aitziber Ugalde‐Olano, Maite Zufiaurre, Ianire Astobiza, Natalia Martin‐Martin, Laura Bozal‐Basterra, Saioa Garcia‐Longarte, Amaia Zabala‐Letona, Sofia Rey, Aida Santos‐Martin, Miguel Unda, Ana Loizaga‐Iriarte, Mariona Graupera, Paolo Nuciforo, Arkaitz Carracedo, Isabel Mendizabal   +16 more
wiley   +1 more source

Molecular Docking Appraisal of Phytochemicals as Potential Inhibitors of PI3K/Akt Pathway for Breast Cancer Treatment

Bioinformatics and Biology Insights
Introduction: Breast cancer (BC) is a heterogeneous disease involving a network of numerous extracellular signal transduction pathways. The phosphoinositide 3-kinase (PI3K)/serine/threonine kinase (Akt)/mechanistic target of rapamycin (mTOR) pathway is ...
Magdalene Eno Effiong, Mercy Bella-Omunagbe, Israel Sunmola Afolabi, Shalom Nwodo Chinedu   +3 more
doaj   +1 more source

Therapeutic Potential of Autophagy in Glioblastoma Treatment With Phosphoinositide 3-Kinase/Protein Kinase B/Mammalian Target of Rapamycin Signaling Pathway Inhibitors

Frontiers in Oncology, 2020
Glioblastoma (GB) is the most malignant and aggressive form of brain tumor, characterized by frequent hyperactivation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway.
Qin Xia, Mengchuan Xu, Pei Zhang, Liqun Liu, Xinyi Meng, Lei Dong   +5 more
doaj   +1 more source

Wortmannin, a Widely Used Phosphoinositide 3-Kinase Inhibitor, also Potently Inhibits Mammalian Polo-like Kinase [PDF]

Chemistry & Biology, 2005
Polo-like kinases (PLKs) play critical roles throughout mitosis. Here, we report that wortmannin, which was previously thought to be a highly selective inhibitor of phosphoinositide (PI) 3-kinases, is a potent inhibitor of mammalian PLK1. Observation of the wortmannin-PLK1 interaction was enabled by a tetramethylrhodamine-wortmannin conjugate (AX7503 ...
Liu, Yongsheng, Shreder, Kevin R., Gai, Wenzhi, Corral, Sergio, Ferris, Douglas K., Rosenblum, Jonathan S.   +5 more
openaire   +2 more sources

Potential therapeutic targeting of BKCa channels in glioblastoma treatment

Molecular Oncology, EarlyView.
This review summarizes current insights into the role of BKCa and mitoBKCa channels in glioblastoma biology, their potential classification as oncochannels, and the emerging pharmacological strategies targeting these channels, emphasizing the translational challenges in developing BKCa‐directed therapies for glioblastoma treatment.
Kamila Maliszewska‐Olejniczak, Karolina Pytlak, Sandra Jaworowska, Bogusz Kulawiak, Piotr Bednarczyk   +4 more
wiley   +1 more source

Recombinant tissue plasminogen activator protects neurons after intracerebral hemorrhage through activating the PI3K/AKT/mTOR pathway

Neural Regeneration Research
Recombinant tissue plasminogen activator is commonly used for hematoma evacuation in minimally invasive surgery following intracerebral hemorrhage. However, during minimally invasive surgery, recombinant tissue plasminogen activator may come into contact
Jie Jing, Shiling Chen, Xuan Wu, Jingfei Yang, Xia Liu, Jiahui Wang, Jingyi Wang, Yunjie Li, Ping Zhang, Zhouping Tang   +9 more
doaj   +1 more source

The impact of PI3K inhibitors on breast cancer cell and its tumor microenvironment [PDF]

PeerJ, 2018
The phosphoinositide 3-kinase (PI3K) pathway shows frequent aberrant alterations and pathological activation in breast cancer cells. While PI3K inhibitors have not achieved expectant therapeutic efficacy in clinical trials, and several studies provide ...
Hanjiao Qin, Linlin Liu, Shu Sun, Dan Zhang, Jiyao Sheng, Bingjin Li, Wei Yang   +6 more
doaj   +2 more sources

Targeted Therapy of HPV Positive and Negative Tonsillar Squamous Cell Carcinoma Cell Lines Reveals Synergy between CDK4/6, PI3K and Sometimes FGFR Inhibitors, but Rarely between PARP and WEE1 Inhibitors

Viruses, 2022
Human papillomavirus positive (HPV+) tonsillar and base of tongue squamous cell carcinoma (TSCC/BOTSCC) have a favorable outcome, but upon relapse, survival is poor and new therapeutical options are needed.
Ourania N. Kostopoulou, Mark Zupancic, Mariona Pont, Emma Papin, Monika Lukoseviciute, Borja Agirre Mikelarena, Stefan Holzhauser, Tina Dalianis   +7 more
doaj   +1 more source

The PI3Kδ inhibitor roginolisib (IOA‐244) preserves T‐cell function and activity

Molecular Oncology, EarlyView.
Identification of novel PI3K inhibitors with limited immune‐related adverse effects is highly sought after. We found that roginolisib and idelalisib inhibit chronic lymphocytic leukemia (CLL) cells and Treg suppressive functions to similar extents, but roginolisib affects cytotoxic T‐cell function and promotion of pro‐inflammatory T helper subsets to a
Elise Solli, Alessio Bevilacqua, Mathias Wenes, Denis Migliorini, Lars van der Veen, Sigrid S Skånland, Giusy Di Conza, Kjetil Taskén   +7 more
wiley   +1 more source