AI SummaryCD3 bispecific antibodies (CD3-bsAbs) targeting TRP1-positive tumors and CD3-rich tissues are effective in inhibiting tumor growth and inducing antitumor T-cell responses, despite rapid receptor-mediated internalization and decreased available dose. Further optimization of CD3-bsAb therapies is possible based on the pharmacokinetics and mechanism of action of CD3xTRP1.Background CD3 bispecific antibodies (CD3-bsAbs) require binding of both… Continue reading Longitudinal evaluation of the biodistribution and cellular internalization of the bispecific CD3xTRP1 antibody in syngeneic mouse tumor models
Tag: Biochemical Pharmacology
A phase 1 trial of 8‐chloro‐adenosine in relapsed/refractory acute myeloid leukemia: An evaluation of safety and pharmacokinetics
Abstract Background This study evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of 8-chloro-adenosine (8-Cl-Ado) in patients with relapsed/refractory acute myeloid leukemia (AML). Methods 8-Cl-Ado was administered daily for 5 days; the starting dose was 100 mg/m2, the highest dose tested was 800 mg/m2. The end points were toxicity, disease response, and PK/PD measurements. Results The predominant nonhematologic… Continue reading A phase 1 trial of 8‐chloro‐adenosine in relapsed/refractory acute myeloid leukemia: An evaluation of safety and pharmacokinetics
A phase 1 trial of 8‐chloro‐adenosine in relapsed/refractory acute myeloid leukemia: An evaluation of safety and pharmacokinetics
AI SummaryA study evaluated the safety, pharmacokinetics, and pharmacodynamics of 8-chloro-adenosine in patients with relapsed/refractory acute myeloid leukemia. The study found that the drug had cardiac toxicity and accumulation in patients, but also showed cytoreduction in peripheral blood. Combination strategies may be needed for longer-lasting effects.Abstract Background This study evaluated the safety, pharmacokinetics (PK), and… Continue reading A phase 1 trial of 8‐chloro‐adenosine in relapsed/refractory acute myeloid leukemia: An evaluation of safety and pharmacokinetics
[ASAP] Ligand Sulfur Oxidation State Progressively Alters Galectin-3-Ligand Complex Conformations To Induce Affinity-Influencing Hydrogen Bonds
New tool developed to efficiently predict relative ligand binding affinity in drug discovery
Nature Computational Science (2023). DOI: 10.1038/s43588-023-00529-9″> The framework of PBCNet. Credit: Nature Computational Science (2023). DOI: 10.1038/s43588-023-00529-9 Lead optimization in drug discovery is a challenging process that heavily relies on hypotheses and the experience of medicinal chemists. This often leads to uncertain outcomes and inefficiency. Furthermore, the process is time-consuming and requires significant resources. Therefore,… Continue reading New tool developed to efficiently predict relative ligand binding affinity in drug discovery
Studies on the selectivity of the SARS-CoV-2 papain-like protease reveal the importance of the P2′ proline of the viral polyprotein
The SARS-CoV-2 papain-like protease (PLpro) is an antiviral drug target that catalyzes the hydrolysis of the viral polyproteins pp1a/1ab, so releasing the non-structural proteins (nsps) 1-3 that are essential for the coronavirus lifecycle. The LXGG↓X motif in pp1a/1ab is crucial for recognition and cleavage by PLpro. We describe molecular dynamics, docking, and quantum mechanics/molecular mechanics… Continue reading Studies on the selectivity of the SARS-CoV-2 papain-like protease reveal the importance of the P2′ proline of the viral polyprotein
Antigenicity and receptor affinity of SARS-CoV-2 BA.2.86 spike
Abstract A SARS-CoV-2 Omicron subvariant, BA.2.86, has emerged and spread to numerous countries worldwide, raising alarm because its spike protein contains 34 additional mutations compared to its BA.2 predecessor1. We examined its antigenicity using human sera and monoclonal antibodies (mAbs). Reassuringly, BA.2.86 was not more resistant to human sera than the currently dominant XBB.1.5 and… Continue reading Antigenicity and receptor affinity of SARS-CoV-2 BA.2.86 spike
An enhanced biophysical screening strategy to investigate the affinity of ASOs for their target RNA
The recent and rapid increase in the discovery of new RNA therapeutics has created the perfect terrain to explore an increasing number of novel targets. In particular, antisense oligonucleotides (ASOs) have long held the promise of an accelerated and effective drug design compared to other RNA-based therapeutics. Although ASOs in silico design has advanced distinctively… Continue reading An enhanced biophysical screening strategy to investigate the affinity of ASOs for their target RNA
AdvanTIG-105: a phase I dose escalation study of the anti-TIGIT monoclonal antibody ociperlimab in combination with tislelizumab in patients with advanced solid tumors
Background Ociperlimab, a novel, humanized monoclonal antibody (mAb), binds to T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) with high affinity and specificity. Tislelizumab is an anti-programmed cell death protein 1 mAb. We report results from a phase I, first-in-human, dose escalation study evaluating the safety, pharmacokinetics (PK), and preliminary antitumor activity… Continue reading AdvanTIG-105: a phase I dose escalation study of the anti-TIGIT monoclonal antibody ociperlimab in combination with tislelizumab in patients with advanced solid tumors
Red-light modulated ortho-chloro azobenzene photoswitch for peptide stapling via aromatic substitution
The application of peptide stapling using photoswitchable linkers has gained notable interest for potential therapeutic applications. However, many existing methodologies of photoswitching still rely on the use of tissue-damaging and weakly skin-penetrating UV light. Herein, we describe the development of a tetra-ortho-chloro azobenzene linker that was successfully used for cysteine-selective peptide stapling via SNAr. This… Continue reading Red-light modulated ortho-chloro azobenzene photoswitch for peptide stapling via aromatic substitution