Kinesin spindle protein (KSP) represents a promising target for cancer therapy with a mechanism of action distinct from conventional microtubule agents. We previously identified S-trityl-L-cysteine (S...

The M1 receptor has long been investigated as a promising CNS drug target, yet further research is essential to fully elucidate compound’s Pharmacodynamic (PD) as well as Toxicokinetic (TK) effects. I...

Ferrocenyl–cyclo-(Gly-l-Pro) hybrids as novel inhibitors of ABCB1 and ABCG2 transporters were developed. These organometallic compounds were virtually nontoxic to colon cancer cells, their multidrug-r...

Targeting the capsid protein of the hepatitis B virus (HBV) has emerged as a promising strategy for developing new antiviral therapies. In this study, we report the discovery of a novel series of pyrrole oxo-carboxamide compounds as HBV capsid assembly modulators (CAMs) that block viral replication. Through a process of focused structure–activity relationship (SAR) optimization, we identified compound 12 (VNRX-9945), which exhibited excellent and broad antiviral activity against multiple HBV genotypes in vitro, along with favorable pharmacokinetic profiles across multiple species. Additionally, 12 demonstrated robust efficacy in the adeno-associated virus mouse model of HBV (AAV-HBV) infection. This compound has advanced into Phase 1 clinical trials to evaluate its safety and pharmacokinetics in healthy volunteers, to enable treatment of chronic HBV infections.

This study presents the chemical synthesis and biological evaluation of a series of gold(I)-N-heterocyclic carbene complexes as potential anticancer agents. The compounds demonstrated broad activity a...

Here we harnessed the unexplored binding interface between the 16-residue peptide (P) agonist and death receptor 5 (DR5). P is a solitary peptide ligand that mimics TRAIL (the natural ligand to death receptor) and is reported to control cancer growth in vivo selectively. We delved into the strategic merging of experimental and in silico structure–activity studies via the alanine scanning mutagenesis of P, wherein the disulfide bond was kept intact for structural integrity. Antiproliferative activity studies with these synthetic mutants on HCT116 cells enabled the mapping of the interaction engagement of each residue. Further, in silico docking and MD simulations led us to interpret and model the 3D interface of the binding site. Notably, Trp1, Leu4, Arg7, Ile8, Gln12, and Arg15 were projected experimentally as “hot-spot” residues crucial for primary interactions with DR5, which is predominantly supported via in silico investigations. This study is pivotal for developing new-generation peptide agonists that induce death receptor-mediated apoptosis.

Gastrin-releasing peptide receptor (GRPR) is a promising target for cancer radiotheranostics combining nuclear imaging with targeted radionuclide therapy. Improving the accumulation of radioligands in...

WASHINGTON — The National Academy of Sciences announced today the election of 120 members and 30 international members in recognition of their distinguished and continuing achievements in original res...

TMTP1 is a tumor-homing peptide that selectively targets highly metastatic tumor cells with XPNPEP2 identified as its potential targeting receptor. Although TMTP1-based molecular probes have been expl...

🌟 H3D Q1 Highlights: A Strong Start to the Year! 🌟 The first quarter of the year at H3D has been nothing short of amazing! Stay tuned as we reflect on some key milestones that we are proud of through...

TMTP1 is a tumor-homing peptide that selectively targets highly metastatic tumor cells with XPNPEP2 identified as its potential targeting receptor. Although TMTP1-based molecular probes have been expl...

While the androgen receptor (AR) has long been a molecular target of prostate cancer therapeutics, the estrogen receptor β (ERβ) has more recently become of interest in this area of chemotherapeutic s...