Population pharmacokinetics of iruplinalkib in healthy volunteers and patients with solid tumors.

Iruplinalkib (WX-0593), a selective oral ALK/ROS1 tyrosine kinase inhibitor, was approved in China as first-line therapy for ALK-positive non-small-cell lung cancer (NSCLC) and for the treatment of locally advanced or metastatic ALK-positive NSCLC that has progressed following crizotinib therapy. Pharmacokinetics (PK) data of iruplinalkib have been collected in healthy subjects and patient populations in several studies. We developed a population PK (PopPK) model for describing iruplinalkib plasma concentrations and for evaluating whether dose adjustments are necessary based on demographic factors or disease characteristics.

QL1604 plus paclitaxel-cisplatin/carboplatin in patients with recurrent or metastatic cervical cancer: an open-label, single-arm, phase II trial.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer.

Methods: This was a multicenter, open-label, single-arm, phase II study.

Iruplinalkib (WX-0593) Versus Crizotinib in ALK TKI-Naive Locally Advanced or Metastatic ALK-Positive NSCLC: Interim Analysis of a Randomized, Open-Label, Phase 3 Study (INSPIRE).

Introduction: Iruplinalkib (WX-0593) is a new-generation, potent ALK tyrosine kinase inhibitor (TKI) that has been found to have systemic and central nervous system (CNS) efficacy in ALK-positive NSCLC. We compared the efficacy and safety of iruplinalkib with crizotinib in patients with ALK TKI-naive, locally advanced or metastatic ALK-positive NSCLC.

Methods: In this open-label, randomized, multicenter, phase 3 study, patients with ALK-positive NSCLC were randomly assigned to receive iruplinalkib 180 mg once daily (7-d run-in at 60 mg once daily) or crizotinib 250 mg twice daily.

Efficacy and safety of iruplinalkib (WX‑0593) on non‑small cell lung cancer with fusion: A case report.

The evidence of anaplastic lymphoma kinase (ALK) inhibitor for non-small cell lung cancer (NSCLC) harbouring sperm antigen with calponin homology and coiled-coil domains 1-like ()- fusion was limited. In a previous case report, a Chinese, 44-year-old, female non-smoker with stage IV NSCLC harbouring fusion was treated with crizotinib ± bevacizumab for 23 months (from October 2017 to September 2019) and second-generation ALK inhibitor iruplinalkib for 2.5 months (from October 2019 to January 2020).

Efficacy and safety of iruplinalkib (WX-0593) in ALK-positive crizotinib-resistant advanced non-small cell lung cancer patients: a single-arm, multicenter phase II study (INTELLECT).

Background: Iruplinalkib (WX-0593) is an anaplastic lymphoma kinase (ALK)/c-ros oncogene 1 (ROS1) tyrosine kinase inhibitor. Here we reported the single-arm, phase II study (INTELLECT) results of the efficacy and safety of iruplinalkib for ALK-positive crizotinib-resistant advanced non-small cell lung cancer (NSCLC) patients.

Methods: ALK-positive crizotinib-resistant advanced NSCLC patients aged ≥18 years, with Eastern Cooperative Oncology Group performance status of 0-2 were eligible.

Hyperglycemia decreases anti-cancer efficiency of Adriamycin via AMPK pathway.

The authors and journal apologise for an error in the above paper, which appeared in volume 25 part 11, pages 955–966. The error relates to the artwork of Fig. 5 on page 963, in which the blots given in panel E were mistakenly replicated in panel F.

Hyperglycemia decreases anti-cancer efficiency of Adriamycin via AMPK pathway.

Accumulating clinical evidence indicates that diabetic liver cancer patients are less sensitive to intra-arterial chemotherapy than non-diabetic cancer patients. However, the underlying mechanism remains largely uncharacterized. Here, we report that hyperglycemia inhibits AMPK pathway and subsequently reduces ADR induced DNA damage, resulting in decreased chemotherapeutic sensitivity of Adriamycin (ADR).

Neohesperidin Exerts Lipid-Regulating Effects in vitro and in vivo via Fibroblast Growth Factor 21 and AMP-Activated Protein Kinase/Sirtuin Type 1/Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1α Signaling Axis.

The purpose of this study is to prove the lipid-regulating effects of neohesperidin (NHP) and explore the potential mechanisms related to fibroblast growth factor 21 (FGF21) and AMP-activated protein kinase (AMPK). Free fatty acids (FFAs)-induced lipid-accumulated HepG2 cells, acutely egg yolk-induced dyslipidemia and chronically diet-induced obese (DIO) model mice were treated with NHP. Biochemical analyses were carried out to determine the lipid profiles.

Effects and molecular mechanisms of the antidiabetic fraction of Acorus calamus L. on GLP-1 expression and secretion in vivo and in vitro.

Ethnopharmacological Relevance: The radix of Acorus calamus L. (AC) is widely used in diabetes therapies in traditional folk medicine from America and Indonesia, and we have previously reported that the ethyl acetate fraction of AC (ACE) acts as an antidiabetic through insulin sensitizing, insulin releasing and alpha-glucosidase inhibitory activities. The present study is designed to investigate the effects and molecular mechanisms of ACE on glucagon-like peptide-1 (GLP-1) expression and secretion related to its hypoglycemic effects.

Synthesis and biological evaluation of novel benzyl-substituted (S)-phenylalanine derivatives as potent dipeptidyl peptidase 4 inhibitors.

A series of novel benzyl-substituted (S)-phenylalanine derivatives were synthesized and evaluated for their dipeptidyl peptidase 4 (DPP-4) inhibitory activity and selectivity. It was found that most synthesized target compounds were potent DPP-4 inhibitors with IC50 values in 3.79-25.

A novel indole derivative compound GY3 improves glucose and lipid metabolism via activation of AMP-activated protein kinase pathway.

The AMP-activated protein kinase (AMPK) is a ubiquitously expressed serine/threonine protein kinase that functions as an intracellular fuel sensor. It has been demonstrated to mediate the activities of a number of pharmacological and physiological factors that exert beneficial effects on type2 diabetes mellitus. GY3 is a novel synthesized indole compound derived from indomethacin, a non-steroid anti-inflammatory drug.

Design, synthesis and biological evaluation of novel imidazolone derivatives as dipeptidyl peptidase 4 inhibitors.

A series of novel imidazolone derivatives were designed and synthesized via a rational drug design strategy. These compounds were obtained from 3-substituted imidazolidine-2,4-dione through alkylation, formylation, dehydration, and amination. The structures were characterized by (1)H NMR, (13)C NMR, and MS.

Insulin releasing and alpha-glucosidase inhibitory activity of ethyl acetate fraction of Acorus calamus in vitro and in vivo.

Ethnopharmacological Relevance: The radix of Acorus calamus L. (AC) is widely used in the therapy of diabetes in traditional folk medicine of America and Indonesia, and we previously reported the insulin sensitizing activity of the ethyl acetate fraction of AC (ACE).

Aim Of The Study: To investigate the insulin releasing and alpha-glucosidase inhibitory activity of ACE in vitro and in vivo.