Radiosynthesis and PET evaluation of [18F]Fuzuloparib as a PARP-targeted imaging agent in breast cancer.

New UHPLC-MS/MS method for simultaneously determination of cis-trans isomers N-isobutyl-2E,4E,8Z,10E/Z-dodecatetraenamide from Asari Radix and the differential metabolites in rat plasma: Application in metabolic stability and pharmacokinetics study.

The therapeutic potential of scaffold containing substituted amine derivatives in the drug design of antidepressant compounds.

Fine-tuning 5-HT7 receptor selectivity, inverse agonism, and metabolic stability of new (aryloxy)ethyl-piperidines toward antidepressant and pro-cognitive properties.

Recent advances in bioactive coumarin scoparone: A comprehensive review.

TRPC6 inhibition by Z3571: A structure-based strategy to ameliorate glomerular and tubular dysfunction in chronic kidney disease.

Precision deuteration at metabolically vulnerable sites of pharmaceuticals can enhance drug stability and therapeutic efficacy, yet existing methods often suffer from poor selectivity and inefficiency. Here, we report an electricity-driven bromine-mediated deuteration strategy that enables late-stage site-selective deuteration of pharmaceuticals using D2O as the deuterium source. This approach involves a two-step process: (i) bromination of labile C-H bonds using Br2, followed by (ii) electricity-driven deuterodebromination using a palladium membrane reactor. This design leverages in situ Br2 generation at the anode and selective deuterium permeation through the palladium membrane cathode, thereby significantly improving atom economy and energy efficiency. Our method achieves nearly complete conversion and >90% deuterium incorporation for a range of aryl, heteroaryl, benzylic, and unactivated alkyl bromides, including ten marketed drug molecules. Furthermore, gram-scale synthesis of D-clonidine demonstrates the scalability of this approach. By integrating high selectivity, broad substrate scope, and operational efficiency, this method offers a practical solution for deuterated drug synthesis, with potential applications in pharmaceutical development and metabolic stabilization.

Review of peptidomimetic vinyl sulfones targeting cysteine proteases and proteasomes.

Prodrug strategy: molecular design for improving oral drug absorption.

Discovery and validation of LAGi-DEL: A nanomolar LAG-3 inhibitor that reverses immune suppression in tumor-immune co-culture models.

Comprehensive identification and characterization of in vitro and in vivo metabolites of the novel GLP-1 receptor agonist danuglipron using UHPLC-QToF-MS/MS.

Synthesis of amide-linked panaxadiol-indolinedione derivatives: A novel NSD2/H3K36me2 epigenetic modulator with significant antitumor efficacy.

Towards next-generation 5-hydroxytryptamine 2C receptor modulators: Greener synthesis and evaluation of novel isocoumarin derivatives as PAAMs of 5-HT2CR.

Reactivity, bioactivity, and antileishmanial activity of dihydrosyrindine and syringine: Modelling, cytotoxicity, molecular docking, molecular dynamics, and MM-GBSA analyses.

Discovery of potent indole-2-one-based BRD4 PROTACs for the treatment of acute myeloid leukemia.

Development and evaluation of [18F]AlF-NOTA-RIDGE11: A novel retro-inverso peptide PET probe for EGFR imaging.

Structural optimization and biological evaluation of 5-fluoro-7H-pyrrolo[2,3- d]pyrimidine derivatives as potent FAK inhibitors for the treatment of triple negative breast cancers (TNBC).

In this study, we investigated the effects of aminated quinolinequinones (AQQ6-16) on cancer cell lines previously selected by the National Cancer Institute (NCI). Analysis of the NCI-60 screening data from the Developmental Therapeutics Program (DTP) of the NCI revealed that 11 AQQs exhibited significant growth inhibitory activity across multiple cancer cell lines and were subsequently advanced to the five-dose assay. Most AQQs effectively suppressed the proliferation of all leukemia cell lines in the single-dose and five-dose assays. Encouraged by these findings, we further examined the cytotoxic effects of selected AQQs (AQQ6 and AQQ9) in three human cancer cell lines, including HCT-116 (colon cancer), DU-145 (prostate cancer), and MDA-MB-231 (breast cancer), as well as in a normal cell line (HUVEC). Among the tested compounds, AQQ6 demonstrated the highest potency against DU-145 cells, with an IC50 value of 3.13±0.15µM. To gain mechanistic insights, the effects of AQQ6 on apoptosis, cell cycle distribution, and oxidative stress were evaluated. AQQ6 inhibited DU-145 cell proliferation by inducing apoptosis/necrosis, accompanied by G0/G1 phase cell cycle arrest. In metabolic stability assays using human liver microsomes, AQQ6 exhibited relatively low intrinsic clearance (Clint) and an improved half-life (T1/2) compared to verapamil. However, pharmacokinetic studies in rats indicated poor oral bioavailability (%F=4.2), likely due to extensive hepatic metabolism in rat liver microsomes. Molecular dynamics simulations targeting MAPK8, the protein likely involved in AQQ6 activity, were conducted to elucidate molecular-level binding interactions.

Chiral pool synthesis of enantiomerically pure morphan derivatives with κ receptor affinity from (S)-perillaldehyde.

Discovery of novel potent indazole-based FXR agonists via scaffold hopping for MASH treatment.