- |||||||||| nemiralisib (GSK2269557) / GSK
Clinical, PK/PD data, Journal: A multicentre, randomised, double-blind, placebo-controlled, crossover study to investigate the efficacy, safety, tolerability and pharmacokinetics of repeat doses of inhaled nemiralisib in adults with persistent, uncontrolled asthma. (Pubmed Central) - Oct 8, 2019 Further studies will investigate the potential efficacy of nemiralisib in patients with asthma with other specific more severe phenotypes, including those who are colonised with bacteria and frequently exacerbate. .
- |||||||||| ME-401 / MEI, Kyowa Hakko Kirin
Clinical, PK/PD data, Journal: Safety, Pharmacokinetics, and Pharmacodynamics of ME-401, an Oral, Potent, and Selective Inhibitor of Phosphatidylinositol 3-Kinase P110δ, Following Single Ascending Dose Administration to Healthy Volunteers. (Pubmed Central) - Oct 8, 2019 P1 ME-401 60 mg, administered once daily, was selected as the starting dose for patient studies. ClinicalTrials.gov identifier: NCT02521389.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Overcoming Target Driven Fratricide for T Cell Therapy. (Pubmed Central) - Oct 8, 2019 The first focused upon the inclusion of a Phosphoinositol-3-Kinase inhibitor (LY294002) into the production process...By means of targeted inhibition of NKG2D expression or generic inhibition of enzyme function, target-driven CAR T fratricide can be overcome. These strategies have been incorporated into on-going clinical trials to enable a highly efficient and reproducible manufacturing process for NKG2D-CAR T cells.
- |||||||||| Avastin (bevacizumab) / Roche, paclitaxel / Generic Mfg.
Review, Journal: PI3K/AKT/mTOR inhibitors for advanced or recurrent endometrial cancer. (Pubmed Central) - Oct 8, 2019 In a recurrent disease setting, mTOR inhibitors may result in improved progression-free survival, but we found no clear benefit in overall survival or tumour response rate. We await the publication of at least five ongoing studies investigating the role of PI3K/AKT/mTOR inhibitors in advanced or recurrent endometrial cancer before any conclusions can be drawn on their use.
- |||||||||| Journal: Hypothalamic dopamine signaling regulates brown fat thermogenesis. (Pubmed Central) - Oct 5, 2019
We further demonstrate that, as early as 3 months after onset of treatment, patients treated with the D2R agonist cabergoline experience an increase in energy expenditure that persists for one year, leading to total body weight and fat loss through a prolactin-independent mechanism. Our results may provide a mechanistic explanation for how clinically used D2R agonists act in the CNS to regulate energy balance.
- |||||||||| Journal: MFG-E8 reverses microglial-induced neurotoxic astrocyte (A1) via NF-κB and PI3K-Akt pathways. (Pubmed Central) - Oct 4, 2019
In the current study, we constructed an Aβ42-activated microglia-conditioned medium to induce A1 astrocytic activation via secretion of interleukin 1α, tumor necrosis factor, and complement component 1q in vitro, and indicated the regulatory role of milk fat globule epidermal growth factor 8 (MFG-E8) on A1/A2 astrocytic alteration through the downregulation of nuclear factor-κB and the upregulation of PI3K-Akt. This study showed that MFG-E8 suppressed A1 astrocytes and holds great potential for the treatment of AD.
- |||||||||| quercetin (LY294002) / Eli Lilly, SP600125 / Celgene
Mechanisms underlying human placental CD34+-derived natural killer cell cytotoxicity against glioblastoma (Prince George's Exhibition Halls AB) - Oct 2, 2019 - Abstract #SITC2019SITC_566; Our results demonstrate the importance of PI3K and JNK pathways in mediating PNK cytotoxicity to GBM cell line targets. These data combined with our receptor profiling on PNK cells establish the rationale for further investigating receptor-ligand interactions that directly modulate PI3K and JNK activity.
- |||||||||| quercetin (LY294002) / Eli Lilly, U0126 / Promega, SP600125 / Celgene
Journal: Myricetin treatment induces apoptosis in canine osteosarcoma cells by inducing DNA fragmentation, disrupting redox homeostasis, and mediating loss of mitochondrial membrane potential. (Pubmed Central) - Oct 2, 2019 Moreover, inhibition of PI3K and MAPK using LY294002, U0126, or SP600125, in addition to myricetin treatment, effectively suppressed cell proliferation compared to treatment with myricetin or each inhibitor alone. Therefore, we concluded that myricetin may be a potentially effective and less toxic therapeutic agent to prevent and control progression of canine osteosarcoma.
- |||||||||| quercetin (LY294002) / Eli Lilly
Preclinical, Journal: Apolipoprotein M Protects Lipopolysaccharide-Treated Mice from Death and Organ Injury. (Pubmed Central) - Oct 2, 2019 Collectively, these findings identified that UBIAD1 protects against OGD/R-induced multiple subcellular organelles injury through PI3K/AKT Pathway. These results suggest that apoM possesses protective properties against LPS-induced organ injuries and could potentially be introduced as a novel therapy for the severe conditions that are consequent to sepsis.
- |||||||||| Review, Journal: The versatile role of curcumin in cancer prevention and treatment: A focus on PI3K/AKT pathway. (Pubmed Central) - Oct 2, 2019
Considered to be the key signaling pathway, the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) pathway therefore represents a key target for cancer therapeutics. In the current review, we focus upon curcumin's targeting of PI3K/AKT in different malignancies to effect inhibition of cancer development and progression.
- |||||||||| sirolimus / generics
Preclinical, Journal: Exogenous H S exerts biphasic effects on porcine mammary epithelial cells proliferation through PI3K/Akt-mTOR signaling pathway. (Pubmed Central) - Oct 2, 2019 Moreover, constitutive activation of Akt pathway via transfection of Akt-CA completely eliminated the inhibition of PMECs proliferation and mTOR signaling pathway, and the change of proliferative genes expression induced by 600 µM NaHS. In conclusion, our findings provided evidence that exogenous H S supplied by NaHS exerted biphasic effects on PMECs proliferation, with stimulation at lower doses and suppression at high dose, through the intracellular PI3 K/Akt-mTOR signaling pathway.
- |||||||||| tyrphostin (AG 490) / EMD Serono, Yissum Research Development Company, quercetin (LY294002) / Eli Lilly, PD98059 / Wayne State University
Preclinical, Journal: Specific effects of neuregulin-1β on the communication between DRG neurons and skeletal muscle cells in vitro. (Pubmed Central) - Oct 2, 2019 These data imply that NRG-1β is essential for the nerve-muscle communication by enhancing growth and modifying phenotypes of the two different kinds of cells. The specific effects produced by NRG-1β add novel interpretation for nerve-muscle communication between sensory neurons and SKM cells.
- |||||||||| Wnt11 combines PI3K and Rho / ROCK signaling in the invasion of breast cancer (M8) - Sep 30, 2019 - Abstract #DGHO2019DGHO_1537;
Our findings suggest that irisin is a novel therapeutic agent for pancreatic cancer. Taken together, our results identified WNT11 as an important tumor protein regulating breast cancer metastasis through integration of PI3K and Rho/Rock signaling.
- |||||||||| Rituxan (rituximab) / Roche, Biogen
Follicular lymphoma (Hall A7) - Sep 30, 2019 - Abstract #DGHO2019DGHO_1009; Many other drugs, including immunotherapies and CAR-T cell therapies, are under investigation. The identification of patients with high medical need and new drugs will improve the therapeutic options in future.
- |||||||||| Campath (alemtuzumab) / Sanofi
T-cell lymphoma (R10) - Sep 30, 2019 - Abstract #DGHO2019DGHO_898; The current management of most PTCL is based on chemotherapy and stem cell transplantation concepts. In the near future, more effective treatments may lead to better therapy outcomes in many PTCL entities.
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