- |||||||||| Journal: Integrative Analysis for Identification of Therapeutic Targets and Prognostic Signatures in Non-Small Cell Lung Cancer. (Pubmed Central) - Apr 19, 2022
On the contrary, high mRNA expressions of CBL, FYN, LRKK2, and SOCS2 were associated with a significantly better prognosis. Furthermore, our drug target analysis for these hub genes suggests a potential use of Trichostatin A, Pracinostat, TGX-221, PHA-793887, AG-879, and IMD0354 antineoplastic agents to reverse the expression of these DEGs in NSCLC patients.
- |||||||||| Journal: Systematic Analysis of Stress Granule Regulators-Associated Molecular Subtypes Predicts Drug Response, Immune Response, and Prognosis in Non-Small Cell Lung Cancer. (Pubmed Central) - Apr 19, 2022
Moreover, our results showed patients in C1 NSCLC had the highest sensitivity to AKT.inhibitor, AZD6482 (PI3K inhibitor)...To better predict the prognosis of NSCLC, we analyzed the correlation between stress granule regulator expression and overall survival time in NSCLC and constructed a Stress Granule Score including EIF2S1, CTSG, EIF4G1, IGF2BP1, PABPC1 to predict the prognosis of NSCLC. Overall, this study for the first time uncovers the effect of stress particles on drug response, immune response, and prognosis, laying a new theoretical foundation for the NSCLC prognosis and treatment.
- |||||||||| CNX-1351 / BMS, TGX-221 / Wuhan University, Pfizer
Journal: Covalent Proximity Scanning of a Distal Cysteine to Target PI3Kα. (Pubmed Central) - Apr 15, 2022
Compounds 19 and 22 thus qualify as specific chemical probes to explore PI3Kα-selective signaling branches. The proposed approach is generally suited to develop covalent tools targeting distal, unexplored Cys residues in biologically active enzymes.
- |||||||||| TGX-221 / Wuhan University, Pfizer, Zydelig (idelalisib) / Gilead
Journal, IO biomarker: IGF-1 regulates astrocytic phagocytosis and inflammation through the p110α isoform of PI3K in a sex-specific manner. (Pubmed Central) - Apr 5, 2022
AG66 suppressed the IGF-1 effect on cytokine expression and counteracted the IGF-1-produced phagocytosis decrease in male reactive astrocytes. Results suggest that sex-differences in the effect of IGF-1 on the AKT-phosphorylation could be due to a lower expression of the p110α in female and that IGF-1-effects on the inflammatory response and phagocytosis of male reactive astrocytes are mediated by p110α/PI3K subunit.
- |||||||||| cisplatin / Generic mfg., temozolomide / Generic mfg.
Journal, IO biomarker: The Role of m5C-Related lncRNAs in Predicting Overall Prognosis and Regulating the Lower Grade Glioma Microenvironment. (Pubmed Central) - Apr 5, 2022
The high-risk group was more sensitive to anti-CTLA4 therapy and to compounds including Temozolomide, Bleomycin, Cisplatin, Cyclopamine, A.443654 (Akt inhibitor), AZD6482 (PI3K inhibitor), GDC0941(PI3K inhibitor), and metformin. We present for the first time a m5C-related lncRNA signature for lower grade glioma patient prognosis and therapy response prediction with validated performance, providing a promising target for future research.
- |||||||||| AG-1296 - Friedrich / Schiller University of Jena, Wuhan University, Zhejiang University
Journal: PDGF-PDGFR network differentially regulates, myogenic cell fate, migration, proliferation, and cell cycle progression. (Pubmed Central) - Apr 1, 2022
PDGFRs inhibitor AG1296 inhibited ERK1/2 and AKT activation, myoblast migration, proliferation, and cell cycle progression induced by PDGF-AB and PDGF-BB...Also, myogenic differentiation reduced the expression of both PDGFRα and PDGFRβ, whereas forced PDGFRα expression impaired myogenesis. Thus, our data highlight PDGF signaling pathway to stimulate satellite cell proliferation aiming to enhance skeletal muscle regeneration and provide a deeper understanding of the role of PDGF signaling in non-fibroblastic cells.
- |||||||||| AZD6482 / AstraZeneca, Wuhan University
SAFETY AND TOLERABILITY OF AZD6482 IN REPERFUSION FOR STROKE (STARS) (E-POSTER LIBRARY) - Mar 12, 2022 - Abstract #ESOC2022ESOC_88;
Mapping unique adaptive signaling responses to isoform-selective PI3K inhibition will help to design better combinative treatments that prevent the induction of selective compensatory signals. If the trial shows safety of the AZD6482, further trials will be conducted to assess its efficacy.
- |||||||||| TGX-221 / Wuhan University, Pfizer
Targeting PIK3CB in glioblastoma (E-Poster Website) - Mar 9, 2022 - Abstract #AACR2022AACR_6839;
This indicates that TGX-211, through p110β inhibition, is able to sensitize resistant cell lines to TMZ therapy. More experiments are ongoing to determine if this effect will also be demonstrated in human-derived GSC’s.
- |||||||||| GSK2636771 / GSK, TGX-221 / Wuhan University, Pfizer, buparlisib (BKM120) / Novartis, Adlai Nortye
Journal: Targeting effector pathways in RAC1-driven malignant melanoma. (Pubmed Central) - Feb 8, 2022
Using these compounds as well as an SRF/MRTF inhibitor (CCG-203971), we observed similar results in vivo, using embryonic zebrafish development as a readout. These results suggest that targeting Group A PAKs, PI3Kβ, and/or SRF/MRTF represent a promising approach to suppress RAC1 signaling in malignant melanoma.
- |||||||||| TGX-221 / Wuhan University, Pfizer
Journal: Inhibitors of Mycobacterium tuberculosis EgtD target both substrate binding sites to limit hercynine production. (Pubmed Central) - Feb 1, 2022
X-ray crystal structures of EgtD-inhibitor complexes confirm that L-Histidine analogs bind solely to the L-Histidine binding site while drug-like inhibitors, such as TGX-221, and S-Glycyl-H-1152 span both the L-Histidine and AdoMet binding sites. These enzyme-inhibitor complexes provide detailed structural information of compound scaffolds useful for developing more potent inhibitors that could shorten Tuberculosis treatment regimens by weakening important bacterial defenses.
- |||||||||| temozolomide / Generic mfg.
Journal: Connexin 43 confers chemoresistance through activating PI3K. (Pubmed Central) - Jan 14, 2022
These two different treatments synergistically inactivate PI3K and sensitize glioblastoma cells to temozolomide in vitro and in vivo. Our study has revealed novel mechanistic insights into Cx43/PI3K-mediated temozolomide resistance in glioblastoma and demonstrated that targeting Cx43 and PIK3CB/p110β together is an effective therapeutic approach for overcoming chemoresistance.
- |||||||||| allogeneic human dental pulp stem cells - Utooth Biological Technology, Wuhan University, Beijing SH Bio / Tech Corporation
Journal: Single-cell characterization of monolayer cultured human dental pulp stem cells with enhanced differentiation capacity. (Pubmed Central) - Dec 25, 2021
Taken together, our study for the first time revealed the cellular composition switch of monolayer cultured hDPSCs compared to the freshly isolated hDPSCs. After in vitro expansion, the MCAM(+)JAG(+)PDGFRA(-) subpopulation resembled the most transcriptional characteristics of fresh hDPSCs which may be beneficial for further tissue regeneration applications.
- |||||||||| AG-1296 - Friedrich / Schiller University of Jena, Wuhan University, Zhejiang University
Preclinical, Journal: iPSC-endothelial cell phenotypic drug screening and in silico analyses identify tyrphostin-AG1296 for pulmonary arterial hypertension. (Pubmed Central) - Jul 14, 2021
Specifically, AG1296 up-regulated small mothers against decapentaplegic (SMAD) 1/5 coactivators, cAMP response element-binding protein 3 (CREB3), and CREB5: CREB3 induced inhibitor of DNA binding 1 and downstream genes that improved vascular function. Thus, drug discovery for PAH can be accelerated by combining phenotypic screening with in silico analyses of publicly available datasets.
- |||||||||| allogeneic human dental pulp stem cells - Utooth Biological Technology, Wuhan University, Beijing SH Bio / Tech Corporation
Trial completion date, Trial primary completion date: Safety and Efficacy Study of Allogeneic Human Dental Pulp Mesenchymal Stem Cells to Treat Severe COVID-19 Patients (clinicaltrials.gov) - Mar 10, 2021
P1/2, N=20, Recruiting,
We conclude that PDGF-BB increases Kir2.1 currents via PDGF-BBRβ through activation of cAMP-PKA signaling in RASMCs. Trial completion date: Mar 2021 --> Dec 2021 | Trial primary completion date: Dec 2020 --> Nov 2021
- |||||||||| AG-1296 - Friedrich / Schiller University of Jena, Wuhan University, Zhejiang University
Journal: Endothelial progenitor cells promote viability and nerve regenerative ability of mesenchymal stem cells through PDGF-BB/PDGFR-β signaling. (Pubmed Central) - Jan 9, 2021
EPCs-derived paracrine factors containing PDGF-BB (platelet-derived growth factor) were detected, and MSCs were pre-treated with PDGF-BB, while co-MSCs were pre-treated with PDGFR inhibitor AG1296...To our knowledge, our study first demonstrates that EPCs promote viability and potential nerve regenerative ability of MSCs through PDGF-BB/PDGFR-β signaling and its downstream PI3K/Akt and MEK/Erk pathways. mTOR acts as a co-mediator in PI3K/Akt and MEK/Erk pathways.
- |||||||||| AG-1296 - Friedrich / Schiller University of Jena, Wuhan University, Zhejiang University
Journal: The cross-talk between TGF-β and PDGFRα signaling pathways regulates stromal fibro/adipogenic progenitors' fate. (Pubmed Central) - Jul 21, 2020
Finally, pharmacological inhibition of PDGFRα activity with AG1296 impaired TGF-β-induced extracellular matrix remodeling, Smad2 signaling, myofibroblast differentiation, and migration of MSCs. Thus, our work establishes a functional cross-talk between TGF-β and PDGFRα signaling pathways that is involved in regulating the biology of FAPs/MSCs.
- |||||||||| temozolomide / Generic mfg.
[VIRTUAL] Developing a new combinational therapy to combat temozolomide resistance in glioblastoma multiforme (Virtual Meeting II: E-Posters) - May 16, 2020 - Abstract #AACRII2020AACR-II_2197;
MTS cell viability assay was used to determine optimum gallein dosage both alone and in combinational therapies in experimental cell lines with variable Cx43 expression rates and TMZ sensitivities. While results in experimental lines have been favorable, additional work is still needed to elucidate the efficacy of the optimized quadruple combination therapy, which will include testing primary GBM patient samples, GBM stem cells, healthy astrocytes and three-dimensional tumor models.
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