Effects of Food on the Pharmacokinetics and Safety of HA121-28 Tablet, a Novel Multi-Targeting Tyrosine Kinase Inhibitor, in Healthy Chinese Subjects: A Phase I Clinical Trial

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 515 - 524

Published: Jan. 1, 2025

HA121-28, a novel multi-targeting tyrosine kinase inhibitor, has dual efficacy against tumor growth and neovascularization. The objectives of this study were to assess the effect high-fat high-calorie food on pharmacokinetic (PK) profile safety HA121-28 tablet in healthy subjects. A single-dose, randomized, open-label, two-period, crossover-designed phase I clinical trial was conducted. Subjects received 200 mg fasted state or with breakfast. effects PK evaluated by using noncompartmental analysis whole-process assessment. Twenty subjects successfully completed trial. geometric mean ratios (GMRs) for peak concentration plasma (Cmax), area under curve from zero time point (AUClast), infinite (AUCinf) postprandially versus 108.45% (98.51% - 119.40%), 105.23% (100.25% 110.47%), 104.14% (97.41% 111.34%), respectively. majority reported adverse events graded as either level 1 2 severity recovered spontaneously without any interventions. exposure not significantly affected food. application can be recommended use both postprandial states.

Language: Английский

New S‐substituted‐3‐phenyltetrahydrobenzo[4,5]thieno[2,3‐d]pyrimidin‐4(3H)‐one scaffold with promising anticancer activity profile through the regulation and inhibition of mutated B‐RAF signaling pathway

Drug Development Research, Journal Year: 2024, Volume and Issue: 85(7)

Published: Oct. 18, 2024

Abstract Novel 3‐phenyltetrahydrobenzo[4,5]thieno[2,3‐ d ]pyrimidine derivatives were synthesized and screened for their antiproliferative activity against a panel of 60 cancer cell lines. Derivatives 5b , 5f 9c showed significant antitumor at single dose with mean growth inhibition 55.62%, 55.79%, 71.40%, respectively. These compounds further investigated HCT‐116, colon line, FHC, normal line. Compound the highest IC 50 = 0.904 ± 0.03 µM SI 20.42 excelling doxorubicin which scored 2.556 0.09 6.19. was also most potent B‐RAF WT mutated V600E 0.145 0.005 0.042 0.002 µM, respectively in comparison vemurafenib 0.229 0.008 0.038 0.001 The cycle analysis that increased population induced an arrest HCT‐116 cells G0‐G1 stage 1.23‐fold. Apoptosis evaluation compound displayed 18.18‐fold elevation total apoptosis to control. content caspase‐3 by 3.52‐fold versus A molecular modeling study determined binding profile interaction active site.

Language: Английский

Pd-catalysed regioselective cross dehydrogenative coupling of quinazolinones with aromatic carboxylic acids

Tetrahedron Letters, Journal Year: 2024, Volume and Issue: 147, P. 155214 - 155214

Published: July 23, 2024

Language: Английский