PARP1 (Poly(ADP-Ribose) Polymerase 1)

High PARP7 expression is associated with estrogen and androgen response, but also with better overall survival and lower cell proliferation.

These findings highlight EVOSYNTH's ability to integrate target-driven generation with practical synthesizability, establishing a scalable framework for multi-target and polypharmacological drug discovery. Our source code and data to reproduce all experiments are publicly available on GitHub at: https://github.com/HySonLab/EvoSynth.

Strategic structural modifications significantly enhance the potency, selectivity, and pharmacokinetics of anti-TNBC agents. Future research should emphasize polypharmacology, advanced delivery strategies, and translational validation to address TNBC heterogeneity.

Collectively, these factorial results provide compelling evidence that propranolol may interact with core oncogenic kinase cluster and potential modulation of the critical signaling cascades implicated in HCC pathogenesis. Collectively, these computational findings support the hypothesis that propranolol possesses the molecular characteristics of a viable therapeutic candidate for HCC, thereby substantiating the need for rigorous experimental and translational investigation to validate its clinical potential.

Furthermore, the same trajectories were used for the Binding Free and Total Complex Energies computations, revealing that the complexes were stable. All the studies, from protein energies to docking to simulation and binding free energy, supported the stable complexes; however, experimental studies are necessary before their use.

Furthermore, STX12 mRNA levels were significantly reduced following SF3A1 knockdown, indicating that SF3A1-mediated stabilization of STX12 contributes to apoptosis resistance in CRC cells. Collectively, our findings establish that SF3A1 promotes CRC progression by stabilizing STX12 mRNA and selectively inhibiting apoptosis in malignant cells, thereby identifying the SF3A1-STX12 regulatory axis as a novel and selective therapeutic target for CRC.

Regarding α-pipitzol, it exhibited both affinity and an important interaction with PARP-1. Regarding β-pipitzol, it displayed the lowest inhibitory concentration in A549 (64.49 µM); nevertheless, α-isopipitzol presented the lowest inhibitory concentrations, 83.59 µM and 87.85 µM for U37 and MCF-7 cell lines, respectively.

Molecular simulations indicated stable puerarin-cGAS interactions, validated experimentally: puerarin suppressed cGAS-STING activation, reduced oligodendrocyte apoptosis, and promoted remyelination. These results provide new insights into ICH pathogenesis and support puerarin as a potential therapeutic agent for BBB disruption and WMI.

In vitro experiments further demonstrated that APN-A can dramatically reduce the viability of cervical cancer cells, inhibited cell proliferation and migration, and synergistically potentiate the antitumor efficacy of 5-fluorouracil (5-FU). In addition, chemical proteomics enrichment analyses indicated that APN-A shows its antitumor effects primarily by targeting and inhibiting processes such as DNA replication and protein transcription-translation in cancer cells via targeting proteins such as PARP-1, EIF3J, and TCEA1. These findings provide a methodological reference and mechanistic insight for the propynyl modification of APN, and highlight its potential applications in the food industry and drug development.

Furthermore, we identify sodium 2, 2-dichloroacetate (DCA) as a novel inhibitor of USP30, and DCA inhibits CRC serine synthesis and tumor growth. Clinically, USP30, FTO, PHGDH, and PSAT1 levels are highly correlated in CRC tissues. This study provides mechanistic insights into how USP30 senses serine/glycine levels to regulate serine synthesis via the FTO-PHGDH/PSAT1 axis, offering a potential therapeutic strategy for targeting serine/glycine metabolism in cancer.

Mechanistically, targeting ATR signaling at multiple levels induced a replication defect, mitotic abnormalities and apoptotic cell death. Taken together, our results demonstrate the therapeutic benefit of targeting DDR mechanisms in sarcoma with HRDness traits and their potential clinical utility for treating a broader spectrum of tumor types.