- |||||||||| Piqray (alpelisib) / Novartis
Anti-tumor effects of low-dose metronomic vinorelbine in combination with alpelisib in breast cancer cells (exhibition) - Jun 10, 2022 - Abstract #GSS2022GSS_168;
Even lower alpelisib concentrations (10 ng/ml and 100 ng/ml) combined with low-dose metronomic VRL led to a significant reduction of cell viability of PIK3CA -mutated cells, and the anti-tumor activity was comparable with the effects at 1000 ng/ml alpelisib, which is corresponding serum concentration in patients receiving an approved dose of 300 mg/day. Cell viability and proliferation of MDA-MB-231 and BT-549 cells were inhibited by VRL but not by alpelisib alone.
- |||||||||| Journal: Vitamin B6 rescues insulin resistance and glucose-induced DNA damage caused by reduced activity of Drosophila PI3K. (Pubmed Central) - Jun 10, 2022
Taken together, our results provide a strong link between impaired PI3K activity and genomic instability, a crucial relationship that needs to be monitored not only in diabetes due to impaired insulin signaling but also in cancer therapies based on PI3K inhibitors. In addition, our findings confirm the notion that vitamin B6 is a good natural remedy to counteract insulin resistance and its complications.
- |||||||||| Lorbrena (lorlatinib) / Pfizer, Nexavar (sorafenib) / Bayer, Amgen
Review, Journal: Neuroblastoma: Essential genetic pathways and current therapeutic options. (Pubmed Central) - Jun 9, 2022
Despite various therapies including chemotherapy, radiotherapy, immunotherapy and autologous stem cell transplantation in different neuroblastoma risk groups, most patients undergo surgical removal of the tumoral mass. This review is aimed to summarize the updated knowledge about the neuroblastoma, pathogenesis, it's essential genetic pathways and the current available therapeutic options for neuroblastoma.
- |||||||||| Ukoniq (umbralisib) / TG Therap, Briumvi (ublituximab-xiiy) / TG Therap, Neuraxpharm, Calquence (acalabrutinib) / AstraZeneca
Trial suspension, Trial primary completion date, Combination therapy: Acalabrutinib, Umbralisib, and Ublituximab for the Treatment of Previously Untreated Mantle Cell Lymphoma (clinicaltrials.gov) - Jun 9, 2022
P2, N=27, Suspended,
This review is aimed to summarize the updated knowledge about the neuroblastoma, pathogenesis, it's essential genetic pathways and the current available therapeutic options for neuroblastoma. Recruiting --> Suspended | Trial primary completion date: Mar 2023 --> Sep 2022
- |||||||||| ipatasertib (RG7440) / Roche, samotolisib (LY3023414) / Eli Lilly, capivasertib (AZD5363) / Otsuka, AstraZeneca
Review, Journal, IO biomarker: PTEN-PI3K pathway alterations in advanced prostate cancer and clinical implications. (Pubmed Central) - Jun 8, 2022
A key challenge is the importance of PI3K/AKT/mTOR signaling in noncancerous tissues, leading to predictable but often severe toxicities at therapeutic doses. Further advances in selective pharmacologic inhibition of the PI3K/AKT/mTOR pathway in tumors, development of rational combinations, and appropriate biomarker selection to identify the appropriate tumor- and patient-specific vulnerabilities will be required to optimize clinical benefit from therapeutic targeting of this pathway.
- |||||||||| Journal: miR-382-5p promotes cell invasion in hepatocellular carcinoma by targeting PTEN to activate PI3K/Akt signaling pathway. (Pubmed Central) - Jun 8, 2022
Further advances in selective pharmacologic inhibition of the PI3K/AKT/mTOR pathway in tumors, development of rational combinations, and appropriate biomarker selection to identify the appropriate tumor- and patient-specific vulnerabilities will be required to optimize clinical benefit from therapeutic targeting of this pathway. miR-382-5p can activate the PI3K/Akt signaling pathway by targeting PTEN and promote HCC cell invasion.
- |||||||||| LY294002 / Eli Lilly
Journal: Formononetin Improves the Survival of Random Skin Flaps Through PI3K/Akt-Mediated Nrf2 Antioxidant Defense System. (Pubmed Central) - Jun 8, 2022
Co-treatment with formononetin and LY294002 (15 mg/kg), a potent Phosphatidylinositol-3-kinase (PI3K) inhibitor, which aborted nuclear Nrf2 expression and phosphorylated Akt, indicating that formononetin-mediated Nrf2 activation was related to PI3K/Akt pathway...We highlighted the antioxidant effects of formononetin since the Nrf2 system was activated. Therefore, formononetin might be a promising candidate drug that can enhance survival of skin flaps.
- |||||||||| Journal: 2020-2021 Drug Updates in Hematologic Malignancies. (Pubmed Central) - Jun 8, 2022
During JADPRO Live Virtual 2021, Kirollos Hanna, PharmD, BCPS, BCOP, discussed the label indications of drugs and biologics in hematologic malignancies approved from late 2020 to late 2021, including mechanisms of action and various safety profiles so advanced practitioners can manage and treat patients safely with these new and approved therapeutic agents. In particular, CAR T-cell therapies were approved across many hematologic malignancies, along with PI3K inhibitors, anti-CD38 monoclonal antibodies, and immunotherapies.
- |||||||||| Journal: SMER28 Attenuates PI3K/mTOR Signaling by Direct Inhibition of PI3K p110 Delta. (Pubmed Central) - Jun 5, 2022
Lastly, in B cell lymphoma cells, which predominantly depend on tonic signaling through PI3Kδ, apoptosis upon SMER28 treatment is profound in comparison to non-hematopoietic cells. This indicates SMER28 as a possible drug candidate for the treatment of diseases that derive from aberrant PI3Kδ activity.
- |||||||||| Matulane (procarbazine hydrochloride) / Leadiant Biosci
Review, Journal: Therapeutic Options in Neuro-Oncology. (Pubmed Central) - Jun 5, 2022
The relevance of the immune system in carcinogenesis has led to the development of immunotherapy, through vaccination, blocking of immune checkpoints, oncolytic viruses, and adoptive immunotherapy using chimeric antigen receptor T cells. In this article we provide a comprehensive review of the signaling pathways underlying malignant transformation, the therapies currently used in the treatment of malignant gliomas and further explore therapies under development, including several ongoing clinical trials.
- |||||||||| SF2523 / SignalRx, ADYA Consulting
Journal: Combining antiviral drugs with BET inhibitors is beneficial in combatting SARS-CoV-2 infection. (Pubmed Central) - Jun 4, 2022
We recently showed that SF2523, a dual activity small molecule that inhibits PI3K and BRD4, acts synergistically with the antiviral drugs remdesivir and MU-UNMC-2. Our findings suggest that the mTOR pathways are necessary for SARS-CoV-2 pathogenesis in human cells and targeting PI3K/BET (bromodomain and extra-terminal domain proteins) alone or combined with antiviral therapies is beneficial in mitigating SARS-CoV-2 and its variants of concern (VOCs).
- |||||||||| Review, Journal: The role of the PI3K/AKT signalling pathway in the corneal epithelium: recent updates. (Pubmed Central) - Jun 4, 2022
Overall, upon activation by growth factors and NK-1, PI3K/AKT signalling promotes the proliferation, migration, and anti-apoptosis of CECs, and these processes can be regulated by ROS in a concentration-dependent manner. Moreover, PI3K/AKT signalling pathway is inhibited in CECs from individuals with DK and DED, but is overactivated by keratitis.
- |||||||||| LY294002 / Eli Lilly
Journal: Hydrogen Repairs LPS-Induced Endothelial Progenitor Cells Injury via PI3K/AKT/eNOS Pathway. (Pubmed Central) - Jun 4, 2022
H also restored levels of phosphor-AKT (p-AKT), eNOS and phosphor-eNOS (p-eNOS) suppressed by LPS. LY294002 significantly inhibited the increase of p-AKT and eNOS and p-eNOS expression exposed by H. L-NAME significantly inhibited the increase of eNOS and p-eNOS expression induced by H. H repairs the dysfunctions of EPCs induced by LPS, which is mediated by PI3K/AKT/eNOS signaling pathway.
- |||||||||| Aliqopa (copanlisib) / Bayer
P1 data, PK/PD data, Clinical Trial,Phase I, Journal: A phase I pharmacokinetic study of copanlisib in Chinese patients with relapsed indolent non-Hodgkin lymphoma. (Pubmed Central) - May 31, 2022
P1
Seven out of 12 evaluated patients achieved partial response, resulting in an overall response rate of 58.3% Copanlisib was well tolerated in Chinese patients with relapsed or refractory iNHL at the dose of 60 mg and demonstrated encouraging disease control, thus warranting further clinical investigation. NCT03498430 (April 13, 2018).
- |||||||||| LY294002 / Eli Lilly
Preclinical, Journal: Melatonin ameliorates nickel induced autophagy in mouse brain: diminution of oxidative stress. (Pubmed Central) - May 31, 2022
The presence of inhibitors effectively demonstrates that, within the PI3K/AKT/mTOR pathway, autophagy occurs. In conclusion, these data suggest that Ni causes oxidative stress damage and induces autophagy within the mouse brain by inhibiting the PI3K/AKT/mTOR pathway, and that Mt can effectively alleviate the oxidative stress caused by Ni, and reducing Ni induces autophagy in the mouse brain through the PI3K/AKT/mTOR pathway.
- |||||||||| LY294002 / Eli Lilly
Journal: Role of Chitinase-3-like Protein 1 in Cardioprotection and Angiogenesis by Post-Infarction Exercise Training. (Pubmed Central) - May 30, 2022
Furthermore, HUVEC cells were treated in vitro with AMPK agonist-AICAR (a putative pharmacological memetic of exercise), recombinant human CHI3L1, PAR2 receptor blocker (AZ3451), and PI3K inhibitor (LY294002), respectively...AICAR increased HUVEC tubules formation and upregulated CHI3L1 and PAR2 and these changes were attenuated by PAR2 blocker. In conclusion, post-MI exercise training can effectively activate CHI3L1/PAR2 signaling, which led to the improved myocardial function and enhanced cardiac angiogenesis in the infarcted heart.
- |||||||||| Journal: Frequent 4EBP1 Amplification Induces Synthetic Dependence on FGFR Signaling in Cancer. (Pubmed Central) - May 30, 2022
These mRNAs are among the top 200 translation targets and are highly enriched for structure and sequence motifs in their 5'UTR, which depends on the 4EBP1-EIF4E activity. In summary, we identified the translational targets of 4EBP1-EIF4E that facilitate the tumor suppressor function of 4EBP1 in cancer.
- |||||||||| Journal: How Phosphofructokinase-1 Promotes PI3K and YAP/TAZ in Cancer: Therapeutic Perspectives. (Pubmed Central) - May 30, 2022
Consistently, in various cultured cancer cells (including melanoma, sarcoma, hematologic, and epithelial cancer cells), this "citrate strategy" efficiently inhibits the IGFR1/AKT pathway, promotes PTEN activity, reduces Bcl-xL and MCL1 expression, and increases sensitivity to standard chemotherapy. It also inhibits the development of sarcoma, pancreatic, mammary HER and lung RAS-driven tumors in mice without apparent toxicities.
- |||||||||| LY294002 / Eli Lilly
Journal: Transcription Factor E2F1 Exacerbates Papillary Thyroid Carcinoma Cell Growth and Invasion via Upregulation of LINC00152. (Pubmed Central) - May 29, 2022
In addition, E2F1 induced LINC00152 overexpression, which accelerated cell proliferation, migration, and invasion by activating the PI3K/AKT axis, whereas the administration of LY294002, the inhibitor of PI3K, led to reversal of the same...Our findings highlighted that E2F1 augmented PTC cell proliferation and invasion by upregulating LINC00152 and the PI3K/AKT axis. Our discovery provides therapeutic implications for PTC alleviation.
- |||||||||| elimusertib (BAY 1895344) / Bayer, Aliqopa (copanlisib) / Bayer
Enrollment change, Trial completion date, Trial initiation date, Trial withdrawal, Trial primary completion date, Metastases: BAY1895344 and Copanlisib for the Treatment of Molecularly Selected Patients With Advanced Solid Tumors (clinicaltrials.gov) - May 26, 2022
P1b, N=0, Withdrawn,
Therefore, this study may lay a foundation for the discovery of 3-arylisoquinoline compounds with anti-liver cancer potential. N=86 --> 0 | Trial completion date: Dec 2025 --> Mar 2022 | Initiation date: Dec 2021 --> Mar 2022 | Not yet recruiting --> Withdrawn | Trial primary completion date: Dec 2025 --> Mar 2022
- |||||||||| morphine sulphate / Generic mfg.
Preclinical, Journal: Chemokine CXCL10 regulates pain behaviors via PI3K-AKT signaling pathway in mice. (Pubmed Central) - May 26, 2022
In summary, these findings suggest that PI3K-AKT signaling pathway mediates the effect of CXCL10 on the regulation of morphine analgesia and the release of cytokines in spinal cord. Our study provides a new insight into the mechanism of chemokine-relative pain regulation.
- |||||||||| LY294002 / Eli Lilly
Journal: 27-Hydroxycholesterol induces expression of zonula occludens-1 in monocytic cells via multiple kinases pathways. (Pubmed Central) - May 26, 2022
Drugs that are reported to suppress DC differentiation also inhibited 27OHChol-mediated expression and the localization of ZO-1, indicating the coincidence of ZO-1 upregulation and DC differentiation. These results suggest that ZO-1 is differentially expressed while monocytes differentiate into DCs in the presence of 27OHChol via pathways in which distinct signaling molecules are involved.
- |||||||||| buparlisib (AN2025) / Novartis, Adlai Nortye
Journal: Patient-derived models of brain metastases recapitulate human disseminated disease. (Pubmed Central) - May 26, 2022
Finally, we show by RNA sequencing that human BMs and their matched PDXs have similar transcriptional profiles. Overall, these models of BMs recapitulate the biology of human metastatic disease and can be valuable translational platforms for precision medicine.
- |||||||||| Journal: Phenotypic Screening for Small Molecules that Protect β-Cells from Glucolipotoxicity. (Pubmed Central) - May 25, 2022
These 10 compounds decreased markers of glucolipotoxicity including caspase activation, mitochondrial depolarization, and increased calcium flux. Together, these results provide a path forward toward identifying novel treatments to preserve β-cell viability in the face of glucolipotoxicity.
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