Introduction: Amdizalisib (HMPL-689) is an ATP-competitive PI3Kδ inhibitor currently under investigation for treating Hodgkin's lymphoma. This study aimed to evaluate the metabolism, excretion, pharmacokinetics, and safety profile of amdizalisib in healthy human subjects to support its clinical application.
Methods: This Phase I clinical trial included six healthy Chinese male volunteers who received a single oral dose of 30 mg/100 µCi [C]amdizalisib suspension.
Enhancing the hemostatic efficacy and minimizing blood loss in the body has consistently been a primary objective for researchers. This study improved the hemostatic efficacy and tissue adhesion strength of the hemostatic material by augmenting the aldehyde groups in the side chains of sodium alginate. Additionally, it immobilized the aldehyde-modified sodium alginate onto the surface of the hemostatic material through complexation with iron ions, thereby enhancing its antibacterial properties.
View Article and Find Full Text PDFRefractory bleeding presents a critical, life-threatening challenge, and the goal of medical professionals and researchers has always been to achieve safe and effective hemostasis for bleeding wounds. In this study, we utilized the benefits of a self-expanding cellulose sponge to control incompressible bleeding, which is achieved this by creating a tannic acid/metal ion coating on the surface and within the pores of the sponge to improve its hemostatic effectiveness. The effects of various types and concentrations of metal ions (calcium, magnesium, iron, and zinc) on hemostatic efficiency and biosafety is systematically investigated.
View Article and Find Full Text PDFAmdizalisib, also named HMPL-689, a novel selective and potent PI3Kδ inhibitor, is currently under Phase II clinical development in China for treating hematological malignancies. The preclinical pharmacokinetics (PK) of amdizalisib were extensively characterized and to support the further development of amdizalisib. We characterized the plasma protein binding, blood-to-plasma partition ratio, cell permeability, hepatic microsomal metabolic stability, and drug-drug interaction potential of amdizalisib using experiments.
View Article and Find Full Text PDFHerein we describe the medicinal chemistry efforts that led to the discovery of the clinical-staged Syk inhibitor sovleplenib () via a structure-activity relationship investigation and pharmacokinetics (PK) optimization of a pyrido[3,4-]pyrazine scaffold. Sovleplenib is a potent and selective Syk inhibitor with favorable preclinical PK profiles and robust anti-inflammation efficacy in a preclinical collagen-induced arthritis model. Sovleplenib is now being developed for treating autoimmune diseases such as immune thrombocytopenic purpura and warm antibody hemolytic anemia as well as hematological malignancies.
View Article and Find Full Text PDFObjective: Currently, pre-treatment prediction of patients with pancreatic neuroendocrine tumors with liver metastases (PNELM) receiving surufatinib treatment was unsatisfying. Our objective was to examine the association between radiological characteristics and efficacy/prognosis.
Methods: We enrolled patients with liver metastases in the phase III, SANET-p trial (NCT02589821) and obtained contrast-enhanced computed tomography (CECT) images.
Spleen tyrosine kinase (Syk) is an intracellular tyrosine kinase involved in the signal transduction in immune cells mainly. Its aberrant regulation is associated with diversified allergic disorders, autoimmune diseases and B cell malignancies. Therefore, inhibition of Syk is considered a reasonable approach to treat autoimmune/inflammatory diseases and B cell malignancies.
View Article and Find Full Text PDFBackground: Spleen tyrosine kinase (Syk) inhibitor is a treatment option for primary immune thrombocytopenia. We aimed to evaluate the safety, tolerability, pharmacokinetics, preliminary activity, and recommended phase 2 dose of sovleplenib in patients with primary immune thrombocytopenia.
Methods: This randomised, double-blind, placebo-controlled, phase 1b/2 study was conducted at nine hospitals in China.
Background: Savolitinib, a selective MET inhibitor, showed efficacy in patients with non-small cell lung cancer (NSCLC), including pulmonary sarcomatoid carcinoma (PSC), harbouring exon 14 skipping alteration (ex14).
Objective: To analyse , the association between circulating tumour DNA (ctDNA) biomarkers and clinical outcomes, including resistance, with savolitinib.
Design: A multicentre, single-arm, open-label phase 2 study.
Introduction: Savolitinib has been found to have encouraging antitumor activity and a favorable safety profile in Chinese patients with pulmonary sarcomatoid carcinoma and other NSCLCs with exon 14 skipping alterations ( ex14 positive) at the primary analysis of a phase 2 study. Here, we present the long-term efficacy and safety data of savolitinib, including subgroup analyses.
Methods: This multicenter, single-arm, open-label, phase 2 study in the People's Republic of China enrolled MET inhibitor-naive adults with locally advanced or metastatic ex14-positive NSCLC (NCT02897479).
The mechanical properties of epoxy resin can be enhanced by adding nanofillers into its matrix. This study researches and compares the impacts of adding nanofillers with different dimensions, including two-dimensional boron nitride and zero-dimensional silica, on the mechanical and toughness properties of epoxy resin. At low fractions (0-2.
View Article and Find Full Text PDFAdipose-derived stem cells (ADSCs) are stem cells with multidirectional differentiation potential isolated from adipose tissue. They have the same immunomodulatory effect as bone marrow mesenchymal stem cells in wound repair and immune regulation as bone marrow. The mechanism of action of ADSCs in skin wound repair has not been elucidated.
View Article and Find Full Text PDFBackground: Non-small-cell lung cancer (NSCLC) had poor prognosis in patients with brain metastasis. The trial evaluated the safety and efficacy of epitinib (HMPL-813), an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), for EGFR-mutant NSCLC with brain metastasis.
Patients And Methods: This open-label, dose-expansion phase Ib study (ClinicalTrials.
Aim: To investigate the health-related quality of life (HRQoL) of patients who had neuroendocrine tumors (NETs) from SANET trials.
Methods: Eligible patients were randomized in a 2:1 ratio to receive surufatinib or placebo. HRQoL questionnaires, including the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-G.
Background: Savolitinib has shown good tolerability and preliminary efficacy, but efficacy biomarkers require investigation. The main purpose of this study was to confirm in Chinese patients the recommended phase II dose (RP2D) of savolitinib and to explore overall benefit in tumors bearing c-Met aberration.
Methods: This was an open-label, multi-center, 2-part phase I study.