SLC22A1 (Solute Carrier Family 22 Member 1)

Furthermore, GAB2 overexpression reversed these effects and desensitized cisplatin by activating NF-κB-mediated JNK suppression. Overall, cisplatin actively remodels the OCT1-DNMT1-piR-hsa-30937 axis by regulating piRNA expression, which in turn potentiates cisplatin cytotoxicity by attenuating GAB2-mediated survival signaling in OSCC.

A prognostic signature based on the expression levels of three resistome-associated genes has been defined and can serve as a helpful complementary tool in clinical settings to categorize HCC patients.

Critically, the primary cellular lead 5d (- 29.46 kJ/mol) and the strongest binder 5e (- 31.30 kJ/mol) both surpassed the affinity of the clinical benchmark, Sorafenib (- 28.80 kJ/mol), confirming their high potential as competitive inhibitors...In conclusion, compounds 5d and 5e are validated lead candidates possessing favorable absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, direct cellular cytotoxicity, and a robust computationally modeled dual-action profile. Future research is urgently mandated to perform VEGFR-2-specific functional assays to definitively validate the predicted anti-angiogenic mechanism and conduct in-vivo studies to assess therapeutic efficacy.

Further research is needed on PPI and benign gastrointestinal diseases. Our multi-omics integration reveals tissue-specific PPI pharmacodynamics, identifying targets with dual therapeutic/carcinogenic potential that may explain epidemiological discordances.

We develop first-in-class small molecule inhibitors of Oct1/OCA-B transcription complexes and show that administration into NOD mice also blocks diabetes emergence following α-PD-1 treatment. These results identify OCA-B as a promising therapeutic target for the prevention of autoimmunity and immune-related adverse events (irAEs).

This study highlights the critical influence of the compounds' chemical structure on NET and OCT affinities. Structural modifications that reduce OCT-mediated uptake while maintaining high NET affinity could improve the specificity and theranostic potential of NET-targeting ligands. These findings provide insights for designing next-generation radiotracers with enhanced selectivity and clinical utility.

Imatinib plasma concentration was stabilized by the third month in postoperative patients with GIST. Genetic polymorphisms in ABCG2, SLC22A1, and SLC22A5 (OCTN2) were associated with imatinib plasma concentration, while SLC22A5 (OCTN2) also influenced recurrence rates. These results provide a reference for personalized therapy and concentration monitoring.

Therefore, the rational design of novel metformin derivatives should focus on analogical structures of metformin with functionalities that can increase apoptosis-inducing effects while maintaining appropriate interactions with transmembrane proteins, and thus, have a balanced cellular uptake. The polar ring substituents in the sulfonamide moiety of metformin sulfonamides may offer a potential solution.

SIGNIFICANCE STATEMENT: Coptisine and worenine, bioactive isoquinoline alkaloids from traditional herbs, induce hepatotoxicity via organic cation transporter 1-driven hepatic accumulation and CYP1A2/2D6/3A4-mediated metabolic activation. Our findings underscore the importance of transport- and metabolism-guided safety evaluations of herbal medicines containing these compounds.

These findings provide a robust molecular framework for HCC subtyping and prioritize novel biomarkers and therapeutic targets for further validation. This resource advances the potential for personalized HCC diagnostics and therapies.

Yohimbine potently inhibited CYP2D6 with an IC50 of 0.31 μM, weakly inhibited CYP1A2, CYP2C19, and CYP3A4, and did not inhibit CYP2B6. In conclusion, we have verified that yohimbine inhibits CYP2D6 and demonstrated that it is a substrate of OCT1, OCT2, and OCT3, a weak inhibitor of OCT2 and OCT3, but does not inhibit P-gp, BCRP, OATP1B1, OTP1B3, OATP2B1, and OCT1.

These findings establish AKR1B1 as a critical regulator of lipid metabolism in DPN and identify mangiferin as a promising therapeutic agent to inhibit AKR1B1 activity and restore lipid homeostasis in diabetic neuropathy.