- |||||||||| LY294002 / Eli Lilly
Preclinical, Journal: Resistance training increases insulin-induced vasodilation in the mesenteric artery of healthy rats. (Pubmed Central) - Dec 23, 2021 Forty-eight hours after the last session of the RT, the animals were sacrificed and vascular reactivity to insulin in the absence and presence of LY294002 (phosphatidylinositol 3-kinase inhibitors (PI3K), L-NAME (nitric oxide synthase (NOS) inhibitors) and BQ123 (endothelin A antagonist (ET-A) receptor)...When the Phe response was evaluated, there was a reduction in tension in the RT group compared to the CON group. The results suggest that RT improves vascular reactivity.
- |||||||||| LY294002 / Eli Lilly
Preclinical, Journal: Mild hypothermia protects rat cortical neurons against oxygen-glucose deprivation/reoxygenation injury via the PI3K/Akt pathway. (Pubmed Central) - Dec 22, 2021 When the PI3K inhibitor LY294002 was added, neuronal viability and the expression of pAkt and GLT-1 decreased, and extracellular glutamate concentration increased...There was no significant change in neuronal viability or the expression of pAkt and GLT-1 in the group treated with dihydrokainate, an inhibitor of GLT-1-function, compared with the mild hypothermia + OGD/R (HOGD) group, but extracellular glutamate concentration was increased. Consequently, mild hypothermia promoted glutamate clearance by regulating GLT-1 expression via the PI3K/Akt pathway, providing a neuroprotective effect against OGD/R injury.
- |||||||||| Clinical, Review, Journal: CDK 4/6 and PI3K inhibitors: a new promise for patients with HER2-positive breast cancer. (Pubmed Central) - Dec 22, 2021
Meanwhile, the phosphorylation of Akt and GSK-3β increased significantly and resulted in the inactivation of GSK-3β and alleviation of insulin resistance. Treatment landscape for HER2+ breast cancer is rapidly changing, and CDK4/6 and PI3K inhibitors represent a new promising strategy to improve patients' outcomes.
- |||||||||| LY294002 / Eli Lilly
Journal: Cholesterol Regulates Exosome Release in Cultured Astrocytes. (Pubmed Central) - Dec 22, 2021 The cholesterol-dependent regulation of exosome release was also confirmed by in vivo experiments; that is, exosome levels were significantly reduced in the CSF and blood serum of WT mice that were fed a high-fat diet and had increased cholesterol levels when compared to those in WT mice that were fed a normal diet. These results suggest that exosome release is regulated by cellular cholesterol via stimulation of the PI3K/Akt signal pathway.
- |||||||||| sirolimus / Generic mfg.
Journal: Targeting Phosphoinositide 3-Kinase - Five Decades of Chemical Space Exploration. (Pubmed Central) - Dec 21, 2021 The discovery of wort-mannin as the first potent PI3K inhibitor (PI3Ki) in the 1990s provided rapid identification of PI3K-dependent processes, which drove the discovery of the PI3K/protein kinase B (PKB/Akt)/target of rapamycin (mTOR) pathway...The recognition of PI3K as target for cancer therapy drove subsequently drug development. Here we provide a brief journey through the emerging roles of PI3K to the development of preclinical and clinical PI3Ki candidates.
- |||||||||| Journal: Sishen Pill Maintained Colonic Mucosal Barrier Integrity to Treat Ulcerative Colitis via Rho/ROCK Signaling Pathway. (Pubmed Central) - Dec 21, 2021
In addition, SSP increased p-AMPKα and PTEN proteins expression, decreased Notch1 level, and hinted that activation of the PI3K/Akt signaling pathway was inhibited. In conclusion, SSP effectively treated chronic colitis induced by TNBS, which may have been achieved by inhibiting PI3K/Akt signal to suppress activation of the Rho/ROCK signaling pathway to finally maintain the integrity of the intestinal mucosal barrier.
- |||||||||| parsaclisib (INCB50465) / Incyte
Trial completion date, Trial primary completion date: Open-Label Study of Parsaclisib, in Japanese Participants With Relapsed or Refractory Follicular Lymphoma (CITADEL-213) (clinicaltrials.gov) - Dec 21, 2021 P2, N=40, Recruiting, This study demonstrates that 18β-GA has cardioprotective effects on acute myocardial infarction, which may be related to inhibiting oxidative stress, inflammation, apoptosis via the PI3K/Akt pathway, and reducing cell contractility and Ca concentration via L-type Ca channels. Trial completion date: Mar 2024 --> Sep 2024 | Trial primary completion date: Sep 2023 --> Mar 2024
- |||||||||| Review, Journal: Strategies to Overcome Failures in T-Cell Immunotherapies by Targeting PI3K-δ and -γ. (Pubmed Central) - Dec 21, 2021
We examine an exciting new role for using selective inhibitors of the PI3K δ- and γ-isoforms as modulators of T-cell phenotype and function in immunotherapy. Herein we review the current literature on the implications of PI3K-δ and -γ inhibition in T-cell biology, discuss existing challenges in adoptive T-cell therapies and checkpoint blockade inhibitors, and highlight ongoing efforts and future directions to incorporate PI3K-δ and PI3K-γ as synergistic T-cell modulators in immunotherapy.
- |||||||||| ibrutinib / Generic mfg.
Journal: BTK and PI3K Inhibitors Reveal Synergistic Inhibitory Anti-Tumoral Effects in Canine Diffuse Large B-Cell Lymphoma Cells. (Pubmed Central) - Dec 21, 2021 Comparative variant analysis of RNA-seq data among canine B- and T-lymphoid cell lines and primary B-cell lymphoma samples revealed potentially high-impact somatic variants in the genes that encode PI3K, which may explain why AS-605240 does not singly inhibit the proliferation of cell lines. The combination of ibrutinib and AS-605240 represents a promising approach that warrants further in vivo evaluation in dogs, potentially bearing significant value for the treatment of human DLBCL.
- |||||||||| Isoform-selective PI3-kinase inhibition confers partial resilience to cocaine cessation-induced anxiety-like behavior (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_6683;
Future studies will determine whether suppressing p110β in the dmPFC combats anxiety-like behavior via connections with the claustrum. Our findings suggest that isoform-selective PI3K inhibition mitigates cocaine cessation-elicited anxiety-like behavior, likely via coordinated brain regions and circuits.; Grant Support: NIH Grant GM008602; NIH Grant DA044297; NIH Grant OD011132
- |||||||||| Pi3k/mtor inhibition reduces foamy macrophages after spinal cord injury (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_2115;
Macrophage-specific inhibition of PI3K/mTOR using liposomes showed significant decrease in foamy macrophages at the injury site after a mid-thoracic contusive SCI in 8-10 weeks old female mice (7 dpi: n=9 PBS, n=9 Inhibitor; 28 dpi: n=8 PBS, n=8 Inhibitor). Together, our data suggests that foamy macrophages are important contributors to inflammation after injury and identify PI3K/mTOR pathway in foamy macrophages as a potential therapeutic target for SCI.; Grant Support: The Miami Project to Cure Paralysis/The Buoniconti Fund; NINDS R01NS081040; NINDS F31NS115225
- |||||||||| Curcumin's mechanistic effects on neuroblastoma and glioblastoma (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_1252;
These anticancer activities underscore curcumin's potential as a therapeutic agent in cancers of the nervous system. However, while curcumin is clinically safe, its bioavailability and blood-brain barrier permeability remain important considerations on the path toward clinical trials in GBM and NB.; Grant Support: NPRP 11S-1214-170101 (Qatar National Research Fund)
- |||||||||| Memory disruption and alterations of the PI3K/AKT/mTOR signaling pathway following single kainate induced seizure (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_976;
This study adds to the growing literature which indicates time dependent learning and memory deficits after a single seizure. Additionally, this study indicates there are transient alterations in the mTOR signaling pathway and persistent inflammatory responses within the hippocampus which may play a role in the memory disturbances observed.; Grant Support: NIH Grant R15NS088776
- |||||||||| sirolimus / Generic mfg.
Journal: PI3K/AKT/mTOR Signaling Pathway Is Required for JCPyV Infection in Primary Astrocytes. (Pubmed Central) - Dec 18, 2021 Using RNA sequencing and chemical inhibitors to target PI3K, AKT, and mTOR, we have demonstrated the importance of this signaling pathway in JCPyV infection of primary astrocytes not observed in transformed cells. Collectively, these findings illuminate the potential for repurposing drugs that are involved with inhibition of the PI3K/AKT/mTOR signaling pathway and cancer treatment as potential therapeutics for PML, caused by this neuroinvasive virus.
- |||||||||| Journal, IO biomarker: Induction of PI3K/Akt-Mediated Apoptosis in Osteoclasts Is a Key Approach for Buxue Tongluo Pills to Treat Osteonecrosis of the Femoral Head. (Pubmed Central) - Dec 17, 2021
Furthermore, we determined the apoptosis marker of cleaved(C)-caspase-3, bcl-2, and bax and found that BTP could upregulate the C-caspase-3 and bax expression in osteoclasts and decrease the expression of bcl-2, p-Akt, and p-PI3K in a dose-dependent manner, indicating that BTP could induce PI3K/Akt-mediated apoptosis in osteoclasts to treat ONFH. This study explored the pharmacodynamic basis and mechanism of BTP against ONFH from the perspective of systemic pharmacology, laying a foundation for further elucidating the therapeutic effects of BTP against ONFH.
- |||||||||| Tekturna (aliskiren) / PDL
Journal: Attenuation of atrial remodeling by aliskiren via affecting oxidative stress, inflammation and PI3K/Akt signaling pathway. (Pubmed Central) - Dec 17, 2021 This study explored the pharmacodynamic basis and mechanism of BTP against ONFH from the perspective of systemic pharmacology, laying a foundation for further elucidating the therapeutic effects of BTP against ONFH. ALS may offer cardioprotection in RAP-induced atrial remodeling, which may partly be ascribed to its anti-inflammatory and anti-oxidative stress action and the regulation of PI3K/Akt signaling pathway.
- |||||||||| Zydelig (idelalisib) / Gilead, Aliqopa (copanlisib) / Bayer, Copiktra (duvelisib) / Secura Bio, Yakult Honsha
Clinical, Review, Journal: Can Next-Generation PI3K Inhibitors Unlock the Full Potential of the Class in Patients With B-Cell Lymphoma? (Pubmed Central) - Dec 17, 2021 We discuss a number of attributes that are important to increase the therapeutic potential of newer PI3K inhibitors. More promising results may come from combination trials with these newer PI3K inhibitors, developed to limit toxicities (including long-term adverse events), and other antitumor agents.
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