- |||||||||| allogeneic human dental pulp stem cells - Utooth Biological Technology, Wuhan University, Beijing SH Bio / Tech Corporation
Journal: Peripheral Lysosomal Positioning in Inflamed Odontoblasts Facilitates Mineralization. (Pubmed Central) - Nov 23, 2024
Understanding these multiplicity effects is critical to advancing the clinical translation of stem cell-based therapies for AD. Inflammatory stimuli prompted a relocation of lysosomes in odontoblasts, redistributing them from perinuclear location towards the cell periphery, which in turn facilitated mineralization, potentially via mTORC1 signaling and lysosomal exocytosis.
- |||||||||| allogeneic human dental pulp stem cells - Utooth Biological Technology, Wuhan University, Beijing SH Bio / Tech Corporation
Journal: Role and Molecular Mechanism of miR-586 in the Differentiation of Dental Pulp Stem Cells into Odontoblast-like Cells. (Pubmed Central) - Aug 16, 2024
In this article, human dental pulp stem cells (hDPSCs) were used as samples, and hDPSCs were co-cultured with endothelial progenitor cells (EPCs)...The number of mineralized nodules was significantly increased (P?<?0.05). MiR-586 plays a key regulatory function in DPSCs differentiated into odontoblast-like cells and is associated with specific molecular mechanisms.
- |||||||||| Clinical data, Journal, Machine learning: Machine learning-based integration develops a multiple programmed cell death signature for predicting the clinical outcome and drug sensitivity in colorectal cancer. (Pubmed Central) - Aug 12, 2024
In addition, the high-MPCDI group was more sensitive to AZD1332, Foretinib, and IGF1R_3801, and insensitive to AZD3759, AZD5438, AZD6482, Erlotinib, GSK591, IAP_5620, and Picolinici-acid, which suggests that the MPCDI can guide drug selection for CRC patients. As a new clinical classifier, the MPCDI can more accurately distinguish CRC patients who benefit from immunotherapy and develop personalized treatment strategies for CRC patients.
- |||||||||| Journal, Gene Signature, PD(L)-1 Biomarker, IO biomarker: Identification of a Macrophage marker gene signature to evaluate immune infiltration and therapeutic response in hepatocellular carcinoma. (Pubmed Central) - Jun 7, 2024
Moreover, a low-Macrosig score indicates increased sensitivity to AZD.2281, A.443654, ABT.263, ABT.888, AG.014699 and ATRA, while a high Macrosig score indicates increased sensitivity to AZD6482, AKT inhibitor VIII, AS601245, AZ628, AZD.0530 and AZD6244. A novel scoring system was constructed to guide more effective prognostic evaluation and tailoring therapeutic regimens for HCC patients.
- |||||||||| LY294002 / Eli Lilly, AG-1296 - Friedrich / Schiller University of Jena, Wuhan University, Zhejiang University
Preclinical, Journal: PDGF-AA guides cell crosstalk between human dental pulp stem cells in (Pubmed Central) - Apr 8, 2024
A novel scoring system was constructed to guide more effective prognostic evaluation and tailoring therapeutic regimens for HCC patients. This research demonstrated that PDGF-AA can enhance Cx43-mediated GJIC in DPSCs via the PDGFR-?/PI3K/Akt axis, which provides new cues for dental pulp regeneration from the perspective of intercellular communication.
- |||||||||| TGX-221 / Wuhan University, Pfizer
Journal: SP1 Mediated PIK3CB Upregulation Promotes Gastric Carcinogenesis. (Pubmed Central) - Feb 15, 2024
TGX-221, a PIK3CB-selective inhibitor, which can block this signaling transduction pathway, was found to inhibit the growth of GC cells and induce apoptosis in vitro, implying that it may act as a potential development agent for GC. These collective findings provide a new insight into PI3K/AKT signaling that SP1 may function as an upstream factor on PI3K, forming a new signaling axis to promote the progression of GC or other malignancies.
- |||||||||| Enrollment open: STARS: Safety and Tolerability of Adjunctive TBO-309 in Reperfusion for Stroke (clinicaltrials.gov) - Nov 28, 2023
P2, N=80, Recruiting,
These collective findings provide a new insight into PI3K/AKT signaling that SP1 may function as an upstream factor on PI3K, forming a new signaling axis to promote the progression of GC or other malignancies. Not yet recruiting --> Recruiting
- |||||||||| Rubraca (rucaparib) / Pharma& Schweiz, motesanib (AMG 706) / Takeda, AZD6482 / AstraZeneca, Wuhan University
Journal, PD(L)-1 Biomarker, IO biomarker: A novel stratification framework based on anoikis-related genes for predicting the prognosis in patients with osteosarcoma. (Pubmed Central) - Aug 18, 2023
The low-risk group was sensitive to the immune checkpoint PD-1 inhibitor, and the high-risk group exhibited lower inhibitory concentration values by 50% for 24 drugs, including AG.014699, AMG.706, and AZD6482. The prognostic stratification framework of patients with OS based on ARGs, such as BNIP3 and CXCL12, may lead to more efficient clinical management.
- |||||||||| allogeneic human dental pulp stem cells - Utooth Biological Technology, Wuhan University, Beijing SH Bio / Tech Corporation
Journal: GATA4 inhibits odontoblastic differentiation of dental pulp stem cells through targeting IGFBP3. (Pubmed Central) - Aug 14, 2023
The prognostic stratification framework of patients with OS based on ARGs, such as BNIP3 and CXCL12, may lead to more efficient clinical management. GATA4 inhibited odontoblastic differentiation of HDPSCs via activating the transcriptional activity of IGFBP3, identifying its promising role in regulating HDPSCs odontoblast differentiation and reparative dentinogenesis.
- |||||||||| allogeneic human dental pulp stem cells - Utooth Biological Technology, Wuhan University, Beijing SH Bio / Tech Corporation
Preclinical, Journal: Effects of RNA m6A Writer METTL3 and hDPSCs on the peripheral nerve regeneration: in vitro and in vivo study. (Pubmed Central) - Aug 11, 2023
GATA4 inhibited odontoblastic differentiation of HDPSCs via activating the transcriptional activity of IGFBP3, identifying its promising role in regulating HDPSCs odontoblast differentiation and reparative dentinogenesis. These results demonstrated that RNA m6A participated in the differentiation and proliferation of dental pulp stem cells, and that OE-METTL3 group exhibited the greater ability to improve peripheral nerve regeneration than KD-METTL3 group and hDPSCs group.
- |||||||||| Trial completion date, Trial primary completion date: STARS: Safety and Tolerability of Adjunctive TBO-309 in Reperfusion for Stroke (clinicaltrials.gov) - Aug 7, 2023
P2, N=80, Not yet recruiting,
These results demonstrated that RNA m6A participated in the differentiation and proliferation of dental pulp stem cells, and that OE-METTL3 group exhibited the greater ability to improve peripheral nerve regeneration than KD-METTL3 group and hDPSCs group. Trial completion date: Sep 2024 --> May 2025 | Trial primary completion date: Jun 2024 --> Feb 2025
- |||||||||| TGX-221 / Wuhan University, Pfizer, Rydapt (midostaurin) / Novartis
Journal: Construction of the Interaction Network of Hub Genes in the Progression of Barrett's Esophagus to Esophageal Adenocarcinoma. (Pubmed Central) - Apr 20, 2023
Finally, the results of drug sensitivity analysis based on hub genes showed that drugs such as PI3K inhibitor TGX221, bleomycin, PKC inhibitor Midostaurin, Bcr-Abl inhibitor Dasatinib, HSP90 inhibitor 17-AAG, and Docetaxel may be potential candidates to inhibit the progression of BE to EAC. This study is based on a large number of clinical samples with high credibility, which is useful for revealing the probable carcinogenic mechanism of BE to EAC and developing new clinical treatment strategies.
- |||||||||| AZD6482 / AstraZeneca, Wuhan University
Co-targeting CK1epsilon and PIK3CB/p110beta to treat glioblastoma (Section 43; Poster Board #25) - Mar 14, 2023 - Abstract #AACR2023AACR_2319;
Overall, preliminary results show that co-inhibition of CK1epsilon and PIK3CB/p110? with chemical inhibitors yields synergistic GBM cell death.
- |||||||||| TGX-221 / Wuhan University, Pfizer, BI2536 / Boehringer Ingelheim
Biomarker, Journal: Uses of Vascular Endothelial Growth Factor C as a Lung Adenocarcinoma Prognostic Biomarker. (Pubmed Central) - Mar 10, 2023
The activity of BI-2536 and BRD-A94377914 was positively correlated with VEGF-C. Novel LUAD prognostic biomarkers such as VEGF-C mRNA may aid diagnosis and treatment, and may help identify optimal LUAD populations for therapeutic treatments.
- |||||||||| allogeneic human dental pulp stem cells - Utooth Biological Technology, Wuhan University, Beijing SH Bio / Tech Corporation
Journal: Fabrication of an exosome-loaded thermosensitive chitin-based hydrogel for dental pulp regeneration. (Pubmed Central) - Feb 2, 2023
To address this challenge, exosomes were isolated from human pulp stem cells (hDPSCs) and directly embedded into the HPCH/CW pre-gel to form an exosome-loaded hydrogel (HPCH/CW/Exo)...Meanwhile, in vivo animal experiments revealed the formation of new dental pulp-like tissues in an implanted tooth root model. Therefore, the proposed hydrogel provides a great potential alternative to traditional root canal therapy in dental clinics.
- |||||||||| Journal: Synthetic methodologies and SAR of quinazoline derivatives as PI3K inhibitors. (Pubmed Central) - Jan 18, 2023
Lapatinib, afatinib, gefitinib, erlotinib, idelalisib and copanlisib are quinazoline-based, FDA-approved PI3K inhibitors, while compounds like NVPBYL719, GDC-0032, AZD8186, AZD-6482, etc. are under different stages of clinical trials. In light of the above-mentioned facts, in the present study, we have reported different synthetic approaches, mechanisms of anticancer action, and structure-activity relationship analysis of reported quinazoline derivatives as PI3K inhibitors to help researchers working in the field in designing better and isoform-selective PI3K inhibitors.
- |||||||||| AZD6482 / AstraZeneca, Wuhan University
Journal: Optimization of potential non-covalent inhibitors for the SARS-CoV-2 main protease inspected by a descriptor of the subpocket occupancy. (Pubmed Central) - Dec 6, 2022
Our results suggest that fusidic acid, polydatin, SEN-1269, AZD6482, and UNC-2327 have high binding affinities of more than 23 kcal mol...The molecular optimization of ADZ6482 via reinforcement learning algorithms was carried out to screen out three lead compounds, in which slight structural changes give more considerable binding energies and an occupancy of the S4 subpocket of up to 43%. The energetic occupancy could be a useful descriptor for evaluating the local binding affinity for drug design.
- |||||||||| allogeneic human dental pulp stem cells - Utooth Biological Technology, Wuhan University, Beijing SH Bio / Tech Corporation
Journal: BACH1 regulates the proliferation and odontoblastic differentiation of human dental pulp stem cells. (Pubmed Central) - Nov 25, 2022
Our findings suggest that BACH1 is an important regulator of the proliferation and odontoblastic differentiation of hDPSCs in vitro. Manipulation of BACH1 expression may provide an opportunity to promote the regenerative capacity of hDPSCs.
- |||||||||| TGX-221 / Wuhan University, Pfizer
Journal: Platelet p110β mediates platelet-leukocyte interaction and curtails bacterial dissemination in pneumococcal pneumonia. (Pubmed Central) - Nov 16, 2022
Using a mouse model of Streptococcus pneumoniae-induced pneumonia, we find that both platelet-specific p110β deficiency and pharmacologic inhibition of p110β with TGX-221 exacerbate disease pathogenesis by preventing platelet-monocyte and neutrophil interactions, diminishing their infiltration and enhancing bacterial dissemination...Our results demonstrate that platelet p110β dysfunction exacerbates pulmonary infection by impeding leukocyte functions. Thereby, our findings provide important insights into the immunomodulatory potential of PI3K inhibitors in bacterial infection.
- |||||||||| Xalkori (crizotinib) / Pfizer, TGX-221 / Wuhan University, Pfizer, Gilotrif (afatinib) / Boehringer Ingelheim
Journal: Study on the prognosis, immune and drug resistance of m6A-related genes in lung cancer. (Pubmed Central) - Oct 21, 2022
In conclusion, m6A-related genes are important participants in LC and the expression levels of ZC3H13, CBLL1, ELAVL1 and YTHDF1 are significant for prediction and treatment of LC. Researches of drug resistance based on m6A-related genes need to pay more attention for producing new therapeutic strategies of LC and CBLL1 may contribute to target treatment for further research.
- |||||||||| Trial initiation date: STARS: Safety and Tolerability of Adjunctive TBO-309 in Reperfusion for Stroke (clinicaltrials.gov) - Oct 21, 2022
P2, N=80, Not yet recruiting,
Researches of drug resistance based on m6A-related genes need to pay more attention for producing new therapeutic strategies of LC and CBLL1 may contribute to target treatment for further research. Initiation date: Oct 2022 --> Apr 2023
- |||||||||| Zelboraf (vemurafenib) / Roche, AZD6482 / AstraZeneca, Wuhan University
Journal, PD(L)-1 Biomarker, IO biomarker: PD-L1-Mediated Immunosuppression in Hepatocellular Carcinoma: Relationship with Macrophages Infiltration and Inflammatory Response Activity. (Pubmed Central) - Oct 1, 2022
Notably, given the immunosuppressive and inflammatory microenvironment in HCC, we screened four candidate drugs, including dasatinib, vemurafenib, topotecan and AZD6482, and corroborated in two pharmacogenomics databases, which might have potential therapeutic implications in specific HCC patients. Our results enhanced the understanding of linkage in PD-L1 expression patterns with macrophages and inflammation, which may provide new insight into the pathogenic mechanisms and potential therapeutic strategy for HCC.
- |||||||||| AG-1296 - Friedrich / Schiller University of Jena, Wuhan University, Zhejiang University
The pdgfra-regulating lncrna linc02283 is amplified in high-grade glioma and facilitates gliomagenesis (West/Central Hall) - Sep 28, 2022 - Abstract #SNO2022SNO_404;
Inhibition of PDGFRA signaling using AG1296, represses the high endogenous LINC02283 levels in PDGFRA-mutant GSCs, reduces LINC02283 induced signaling in PDGFRA-wt GSCs, and suppresses cell proliferation in both the cellular models of HGG...Thus, blocking the LINC02283-PDGFRA interaction could be a plausible therapeutic strategy in HGG. Altogether, our results provide strong evidence of lncRNAs as drivers of PDGF Receptor A activity and HGG progression and support the potential of lncRNAs as possible therapeutic targets.
- |||||||||| TGX-221 / Wuhan University, Pfizer, XAV-939 / Novartis
Biomarker, Journal, Tumor Mutational Burden, Tumor microenvironment: SAA1 Expression as a Potential Prognostic Marker of the Tumor Microenvironment in Glioblastoma. (Pubmed Central) - Jun 28, 2022
The altered expression level shifts the primary function of SAA1 from cell cycle and mitosis to immune activity. High expression of SAA1 is associated with poor survival and upregulates the expression of LAIR1 and TNFSF14, thereby deeming it as the drug sensitivity indicator for XAV939, TGX-221, and lapatinib in GBM immune therapy.
- |||||||||| Journal: Novel Diagnostic and Therapeutic Options for KMT2A-Rearranged Acute Leukemias. (Pubmed Central) - Jun 24, 2022
Moreover, IC50 data from analyses of ex-vivo drug sensitivity to small-molecule inhibitors reveals that Foretinib is a promising drug option for AML patients carrying FLT3 activating mutations. Thus, we provide novel and accurate options for the diagnostic screening and therapy of KMT2A-r leukemia, regardless of leukemia subtype.
- |||||||||| AZD6482 / AstraZeneca, Wuhan University
Journal: Integrative metabolomics and transcriptomics analysis reveals novel therapeutic vulnerabilities in lung cancer. (Pubmed Central) - Jun 10, 2022
We demonstrated the clinical utility of this integrated metabolic gene signature in LUAD by using it to guide repurposing of AZD-6482, a PI3Kβ inhibitor which significantly inhibited three genes from the 28-gene signature. Overall, we have integrated metabolomics and transcriptomics analyses to show that LUAD and LUSC have distinct profiles, inferred gene signatures with prognostic value for patient survival, and identified therapeutic targets and repurposed drugs for potential use in NSCLC treatment.
- |||||||||| TGX-221 / Wuhan University, Pfizer
Heparin and heparin proteoglycan-mimetics activate platelets via PEAR1 and PI3Kbeta (Exhibition) - May 13, 2022 - Abstract #ISTH2022ISTH_465;
The response to the heparin proteoglycan-mimetic was abolished by a novel anti-PEAR1 nanobody and by a selective inhibitor of PI3Kbeta, TGX 221. Unfractionated heparin stimulated full aggregation in washed platelets in 4 out of 7 donors after a delay of more than 30 minutes but not in platelet-rich plasma.
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