PTPN1 (Protein Tyrosine Phosphatase Non-Receptor Type 1)

In vivo, CA markedly suppressed the growth of xenograft tumors. Collectively, these findings demonstrate that CA inhibits GC progression by targeting the PTP1B/PI3K/Akt/mTOR-glycolysis axis, revealing a novel mechanism and a potential therapeutic strategy.

MCF-7 studies showed that caffeic acid had an inhibitory effect on cells, but cinnamic acid had this effect only on MCF-7 cells. HB2 cells have shown reduced viability, which is significantly higher than that of MCF-7 cell lines.

We examined the existing landscape of PTP1B inhibitors, highlighting ongoing deficiencies in efficacy, selectivity, and bioavailability that have led to clinical failures. Ultimately, a better understanding of the mechanisms underlying PTP1B expression and its context-dependent influencing tumor behavior is crucial for advancing of cancer prevention and treatment, especially for patients with metabolic risk factors.

AlphaFold-Multimer produced few lysine-accessible poses, whereas Arg69-guided docking enriched degradation-competent geometries via biologically relevant interactions. This framework offers a mechanistically grounded and generalizable strategy for rational PROTAC development across protein targets.

In vivo tumor‑bearing experiments also verified the function of the HMBOX1/PTPN1/AKT1 pathway in HCC development. Taken together, the present findings revealed a new HMBOX1/PTPN1/AKT1 axis that inhibits tumor progression and provides new candidate therapy targets for HCC.

In vivo, DMC administration rescued bone loss and restored bone strength in an ovariectomy (OVX) mouse model. In conclusion, this work establishes DMC as a potent immunomodulatory agent for treating osteoporosis and validates PTP1B as a new pharmacological target within the osteoimmune system.

The experimental results showed that Q1 with an IC50 of 2.45 μM against PTP1B exhibited more than 20-fold greater selectivity for PTP1B than for SHP2. Therefore, our efforts provided a new way to predict the selectivity and activity of small molecules for PTP1B and SHP2.

In therapeutic studies, DCBLD1 knockdown demonstrated substantial antitumor effects in both patient-derived organoid and xenograft models, independent of EGFR mutation status. These findings position DCBLD1 as a promising therapeutic target for LUAD patients, offering a potential strategy that complements current EGFR mutation-based approaches.

KRAS mutations and hyperglycaemia drive O-GlcNAcylation of CLDN18.2 at its C-terminal T204 site. O-GlcNAcylated CLDN18.2 promotes poor prognosis and reduces the effectiveness of CLDN18.2-targeted therapies. Low dose MRTX1133 restores CLDN18.2 membrane localisation by reducing its O-GlcNAcylation and augments CLDN18.2-targeted therapy efficacy, offering a novel combinatorial strategy for KRAS-mutant PDAC.

Thus, we have identified a previously unknown APC/PTPN13/STAT1-dependent tumor immune-suppressive mechanism. The potent tumor-suppressing effect of combining anti-PD1 antibodies with APC11 peptides provides a compelling target and rationale for future development of anti-tumor drugs for patients with CRC.

Additionally, DMB reduced levels of AD-related biomarkers, including BACE-1 (β-secretase 1), amyloid-β, and acetylcholinesterase, indicating its capacity to mitigate oxidative stress and amyloidogenesis. This multidisciplinary approach, integrating in vivo and in-silico methodologies, provides a comprehensive understanding of DMB's neuroprotective effects and underscores its potential as a therapeutic agent for both AD and diabetes.

Washing column-bound GroEL/ES/Fgr with ATP-MgCl2 partially dissociated the chaperone complex, enabling isolation of pure Fgr through subsequent size-exclusion and ion exchange chromatography. This method reliably produced highly pure, active recombinant Fgr, with consistent yields of 1 mg per 2 liters of bacterial culture.