- |||||||||| LY294002 / Eli Lilly
Preclinical, Journal: Activation of TREM2 attenuates neuroinflammation via PI3K/Akt signaling pathway to improve postoperative cognitive dysfunction in mice. (Pubmed Central) - Sep 29, 2022 In BV2 microglial cells, the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 significantly reversed the attenuation of TREM2 activation on lipopolysaccharide (LPS)-induced neuroinflammation and abrogated the protective effect of activated TREM2 against LPS-induced neuronal injury in a microglia/neuron coculture system...These results demonstrate that TREM2 is involved in the regulation of the inflammatory response mediated by microglia and cognitive impairment following surgery. Activation of TREM2 can attenuate neuroinflammation by modulating PI3K/protein kinase B (Akt) signaling, thereby alleviating postoperative learning and memory deficits.
- |||||||||| buparlisib (AN2025) / Novartis, Adlai Nortye
Journal: PI3K Inhibition for Squamous Cell Head and Neck Carcinoma. (Pubmed Central) - Sep 29, 2022 Buparlisib, a potent pan-class I PI3K inhibitor, shows promising efficacy in combination with paclitaxel for advanced head and neck squamous cell carcinoma. Results of the phase III BURAN trial are awaited.
- |||||||||| Journal: Argpyrimidine bonded to RAGE regulates autophagy and cell cycle to cause periodontal destruction. (Pubmed Central) - Sep 29, 2022
APMD-induced autophagy, G0/G1 arrest, pro-inflammatory signals activating and periodontal destruction were reversed by RAGE knockdown while aggravated by PI3K inhibitor. This study provides the first evidence that APMD bind to RAGE to regulate autophagy and cell cycle of PDLCs through the PI3K/AKT/mTOR pathway, thereby promoting periodontal destruction.
- |||||||||| NPT520-337 / EVER Pharma
Novel Combination Therapy Using PI3Kinase Inhibition and Immune Based Therapy for the Treatment of Glioblastoma Multiforme (West/Central Hall) - Sep 28, 2022 - Abstract #SNO2022SNO_533; Based on these observations, we examined the potential of a novel, small molecule PI3K inhibitor GCT.Glio.1 (NPT520-337), which was designed to cross the blood brain barrier, to increase the sensitivity of GBM to immune based therapies and radiation...In conclusion, these results indicate that GCT.Glio.1 may sensitize GBM to immune checkpoint inhibitor and/or radiation therapies. Based on our encouraging pre-clinical data and early results from pre-clinical pharmacology and safety studies, we anticipate filing a pre-Investigational New Drug application (pre-IND) as the next step toward our goal of a clinical trial using this combination therapy.
- |||||||||| GSK2636771 / GSK
Next-generation PI3K inhibitor for glioblastoma treatment (West/Central Hall) - Sep 28, 2022 - Abstract #SNO2022SNO_509; We tested several drugs in an MTS viability assay, including Selectide-18, a scrambled 18-residue negative control peptide, and PI3K inhibitor GSK2636771 to compare levels of cancer cell viability...In conclusion, Selectide-18 is explicitly tailored for p110β-high gliomas and has shown promise to treat high-grade glioma effectively. We believe this model of peptide drug can usher in a new generation of p110β specific PI3K inhibitors.
- |||||||||| Piqray (alpelisib) / Novartis
Sensitizing cancer cells to Tumor Treating Fields (TTFields) by inhibition of PI3K (West/Central Hall) - Sep 28, 2022 - Abstract #SNO2022SNO_428; Overall, this study demonstrated that the PI3K/AKT/mTOR signaling pathway is involved in reduced cancer cell sensitivity to long-term application of TTFields, and that re-sensitization may be achieved with relevant inhibitors. The results provide a rationale for further examining the potential benefit of TTFields concomitant with PI3K inhibitors.
- |||||||||| Ukoniq (umbralisib) / TG Therap, Briumvi (ublituximab-xiiy) / TG Therap, Neuraxpharm, Calquence (acalabrutinib) / AstraZeneca
Trial completion date, Trial primary completion date, Combination therapy: Acalabrutinib, Umbralisib, and Ublituximab for the Treatment of Previously Untreated Mantle Cell Lymphoma (clinicaltrials.gov) - Sep 27, 2022 P2, N=27, Suspended, The results provide a rationale for further examining the potential benefit of TTFields concomitant with PI3K inhibitors. Trial completion date: Mar 2023 --> Sep 2023 | Trial primary completion date: Sep 2022 --> Sep 2023
- |||||||||| palazestrant (OP-1250) / Olema Pharma
Enrollment open, Combination therapy, Metastases: Phase 1b Combo w/ Ribociclib and Alpelisib (clinicaltrials.gov) - Sep 26, 2022 P1b, N=60, Recruiting, Trial completion date: Mar 2023 --> Sep 2023 | Trial primary completion date: Sep 2022 --> Sep 2023 Not yet recruiting --> Recruiting
- |||||||||| gemcitabine / Generic mfg.
Journal: Spatially targeting and regulating tumor-associated macrophages using a raspberry-like micellar system sensitizes pancreatic cancer chemoimmunotherapy. (Pubmed Central) - Sep 24, 2022 To repolarize TAMs and elevate the chemoimmunotherapy outcome against pancreatic cancer, co-loading the TME responsive micellar system with gemcitabine (GEM) and PI3K inhibitor wortmannin (Wtmn) was used to dual target TAMs and tumor cells...By inhibiting the PI3K pathway, the M2-like TAMs were repolarized into M1-like TAMs and then activated antitumor immunity, further synergizing with GEM to suppress tumor growth. This tumor and TAMs dual targeting nanoplatform provides an alternative approach to sensitize chemoimmunotherapy against pancreatic cancer.
- |||||||||| methotrexate / Generic mfg., doxorubicin hydrochloride / Generic mfg.
Journal: Chelerythrine Inhibits Stemness of Cancer Stem-Like Cells of Osteosarcoma and PI3K/AKT/mTOR Signal. (Pubmed Central) - Sep 23, 2022 CHE also exhibited an inhibitory effect on the phosphorylation of PI3K, AKT, and mTOR, which is an upstream regulatory signaling pathway of MMP-2/9. In summary, CSCs derived from U2OS and MG-63 cells, CHE could inhibit the stemness and malignant behaviors of CSCs potentially by inhibiting the PI3K/AKT/mTOR signaling pathway.
- |||||||||| Next Questions: T-Cell Lymphomas () - Sep 22, 2022 - Abstract #SOHO2022SOHO_394;
The exception is represented by brentuximab vedotin, which has an indication in relapsed or refractory anaplastic large cell lymphoma, however with much more disappointing results in other PTCL subtypes...This abstract reviews the available data about 3 classes of agents now under evaluation in active clinical trials: the phosphatidylinositol-3 kinase (PI3K) inhibitors duvelisib and linperlisib; the Janus kinase (JAK) 1 inhibitor golidocitinib (DZD4205); the enhancer of zeste homologs 1 and 2 (EZH1/EZH2) inhibitor valemetostat...Grade 3-4 neutropenia, anemia and thrombocytopenia represented the most frequent adverse events correlated with valemetostat. Conclusion New drugs currently under evaluation in clinical trials, including the novel PI3K inhibitors, JAK1 inhibitors and EZH1/EZH2 inhibitors, may be one of the answers to the burning question: “How can we treat patients with relapsed or refractory PTCL?”
- |||||||||| Journal: Identification of novel mycocompounds as inhibitors of PI3K/AKT/mTOR pathway against RCC. (Pubmed Central) - Sep 22, 2022
The ADME profiles of both were satisfactory based on druglikeness and bioavailability score criteria. Thus, this proposed study identified astrakurkurone and ergosta-4,6, 8-(14) 22-tetraene-3-one as potential anticancer drug candidates, and provides comparative structural insight into their binding to the 3 protein kinases.
- |||||||||| Monjuvi (tafasitamab-cxix) / Incyte, parsaclisib (INCB50465) / Incyte
Enrollment closed, Combination therapy, Pan tumor: topMIND: A Study Evaluating Safety, PK, and Efficacy of Tafasitamab and Parsaclisib in Participants With Relapsed/Refractory Non Hodgkin Lymphoma (R/R NHL) or Chronic Lymphocytic Leukemia (CLL) (clinicaltrials.gov) - Sep 22, 2022 P1b/2a, N=100, Active, not recruiting, Thus, this proposed study identified astrakurkurone and ergosta-4,6, 8-(14) 22-tetraene-3-one as potential anticancer drug candidates, and provides comparative structural insight into their binding to the 3 protein kinases. Recruiting --> Active, not recruiting
- |||||||||| Preclinical, Journal: mTOR pathway mediates endoplasmic reticulum stress-induced CD4 T cell apoptosis in septic mice. (Pubmed Central) - Sep 21, 2022
By analyzing the proteins of mTOR-ERS signaling pathway and the expression of apoptosis-related proteins and genes, we found that mTOR mediated the ER stress induced CD4 T cell apoptosis in Septic mice by negatively regulating the Akt-IRE1-JNK-Caspase 3 signaling cascades. These results indicate that mTOR-Akt-IRE1α-JNK signaling pathway mediated the Endoplasmic reticulum stress induced CD4 T cell apoptosis in Septic mice.
- |||||||||| Journal: Development of selective inhibitors of phosphatidylinositol 3-kinase C2α. (Pubmed Central) - Sep 21, 2022
We demonstrate that acute inhibition of PI3KC2α-mediated synthesis of phosphatidylinositol 3-phosphates by PITCOINs impairs endocytic membrane dynamics and membrane remodeling during platelet-dependent thrombus formation. PITCOINs are potent and selective cell-permeable inhibitors of PI3KC2α function with potential biomedical applications ranging from thrombosis to diabetes and cancer.
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