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[[alternative]]Pyrimidine compounds and their pharmaceutical uses
No full text[[abstract]]本發明提供一種式(I)嘧啶化合物：其式中之變數於本文中進行定義。本發明還揭露一種用嘧啶化合物中之一者治療癌症之方法
作為極光激酶抑制劑的稠合雙環嘧啶化合物
No full text[[abstract]]本發明關於式(I)的稠合雙環嘧啶化合物。本發明也公開一種抑制極光激酶活性的方法，以及一種用這些化合物治療癌症的方法
Fused bicyclic pyrimidine compounds as Aurora kinase inhibitors
No full text[[abstract]]Fused bicyclic pyrimidine compounds of formula (I) defined herein. Also disclosed are a method for inhibiting Aurora kinase activity and a method for treating cancer with these compounds
[[alternative]]Fused bicyclic pyrimidine compounds as aurora kinase inhibitors
No full text[[abstract]]本發明公開了如在此限定的式(I)的稠合多環化合物。本發明也公開了一種抑制蛋白激酶(如極光激酶)活性的方法，以及一種以這些化合物治療蛋白激酶介導的疾病(如癌症)的方法
噻唑烷酮化合物及其用途
No full text[[abstract]]一種包含式(I)化合物的用於治療阿片樣物質受體相關病症的藥物組合物。也公開了使用這種化合物治療阿片樣物質受體相關病症的方法。進一步公開了兩組式(I)的噻唑烷酮化合物：(i)各自具有大於90％對映體過量值的化合物以及(ii)各自經氘取代的化合物
Inhibitors of positive strand RNA viruses
No full text[[abstract]]Methods of treating a disease caused by a positive strand RNA virus. The methods include administering to a subject in need thereof an effective amount of a compound of Formula I or Formula II
Aminothiazole compounds
No full text[[abstract]]Aminothiazole compounds of Formula (I) shown herein and pharmaceutical compositions containing one of such compounds
Thiazole compounds as protein kinase inhibitors
No full text[[abstract]]Thiazole compounds of Formula (I) shown below and pharmaceutical compositions containing one of such compounds: wherein R1 and R2 are defined in the specification. Also disclosed are methods of inhibiting a tyrosine kinase and treating cancer associated with a tyrosine kinase with one of the thiazole compounds
The effect of dopamine receptor D1 (Drd1) gene variants on changes in craving severity during alcohol withdrawal
No full text[[abstract]]Background: Alcohol dependence (AD) is a complex disorder with unclear underlying etiologies. One strategy to understand its pathophysiology involves investigating the behaviors or symptoms, namely subphenotypes, associated with AD. Given that aggression is a prevalent behavior in individuals with AD and is associated with a poor outcome, we attempted to examine the biological underpinnings of aggression as a subphenotype of AD in terms of genetic predisposition. Furthermore, we also explored the impact of genes on craving, a hallmark of AD and AD relapse. Aims & Objectives: This study aimed to identify the association of aggression-related candidate genes with AD. In addition, we also investigated the genetic association with changes in craving severity following 2 weeks of alcohol withdrawal. Method: A total of 210 treatment-seeking patients with AD and 117 healthy controls were recruited in this study. 7 candidate genes were screened based on genome-wide genotyping Axiom Genome-Wide TWB 2.0 Array, included MECOM, AVPR1A, DRD1, DRD2, DRD3, RBOX1, and HTR2A. We followed the Alcohol Craving Questionnaire-Short Form-Revised (ACQ-SF-R) and Obsessive-Compulsive Drinking Scale (OCDS), both of which were used to assess the severity of alcohol craving during withdrawal. Results: Among the candidate genes, we identified a significant association of Dopamine Receptor D1 ( DRD1) gene with AD. The DRD1 single nucleotide polymorphisms (SNPs) (rs12518222, rs144667196, rs4867798, rs686, rs4532, rs5326, and rs265981) were further examined, and we found these SNPs were significantly associated with AD. The minor alleles of rs12518222, rs4867798, rs686, rs4532, rs5326, rs265981 were associated with higher craving scores throughout the withdrawal period. Haplotype-based analyses also demonstrated a significant association of DRD1 gene with less craving alleviation during alcohol withdrawal. Discussion & Conclusion: Our data indicates an association between the aggression-related gene DRD1 and AD within Taiwanese population. Particularly, patients harboring the minor alleles of DRD1 SNPs have a higher risk of AD and display a higher post-withdrawal craving scores compared to those harboring their counterparts. These findings, indicating that DRD1 gene plays a role in the susceptibility to AD and retards craving amelioration during the recovery phase, suggest that aggression might intricately involve neurobiological mechanisms contributing to AD
Updated results from the trastuzumab deruxtecan (T-DXd) 5.4 mg/kg triplet combination of DESTINY-Gastric03 (DG-03): First-line (1L) T-DXd with fluoropyrimidine (FP) and pembrolizumab in advanced/metastatic HER2-positive (HER2+) esophageal adenocarcinoma,
No full text[[abstract]]Background: T-DXd is a HER2-directed antibody-drug conjugate; T-DXd 6.4 mg/kg monotherapy is approved for patients with metastatic HER2+ GC/GEJA who have received a prior trastuzumab-based regimen. Preliminary results from DG-03 Part 2 showed feasibility and promising antitumor activity with 1L T-DXd 6.4 mg/kg (arm D) or 5.4 mg/kg (arm F) with FP and pembrolizumab in patients with esophageal adenocarcinoma/GC/GEJA. T-DXd 6.4 mg/kg and FP with pembrolizumab was associated with higher than expected toxicity; alternatively, early safety data from T-DXd 5.4 mg/kg triplet combination showed a manageable safety profile. We report updated results for arm F from DG-03 Part 2 with an approximate time-matched analysis with arm D. Methods: DG-03 (NCT04379596) is a Phase 1b/2 multicenter, open-label, dose-escalation (Part 1) and -expansion (Parts 2, 3, and 4) study. In Part 2, patients with HER2+ (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization–positive by local testing) esophageal adenocarcinoma/GC/GEJA, irrespective of programmed cell death ligand 1 status, and no prior treatment for metastatic disease were enrolled. In arm D, patients received T-DXd 6.4 mg/kg intravenous (IV) infusion every 3 weeks (Q3W) and FP (5-fluorouracil [5-FU] 600 mg/m2 continuous IV or capecitabine [cape] 1000 mg/m2 twice daily [BID]) with pembrolizumab 200 mg IV Q3W; in arm F, patients received T-DXd 5.4 mg/kg IV Q3W and FP (5-FU 600 mg/m2 continuous IV or cape 750 mg/m2 BID) with pembrolizumab 200 mg IV Q3W.Primary endpoint was confirmed objective response rate by investigator assessment (INV) per RECIST 1.1. Secondary endpoints included duration of response by INV and progression-free survival by INV. Safety and tolerability were also assessed. Results: A time matched analysis was performed to compare the efficacy of arm D (n=43), data cut-off (DCO) October 27, 2022, and arm F (n=32), DCO May 6, 2024, given the limited follow up of the 5.4mg/kg. The median duration of follow up for the two cohorts was 4.1 months and 4.6 months for arm D and arm F, respectively. Objective response rate for arm D was 41.9% and 59.4% for arm F. Median PFS was 6.4 months (95% CI: 5.0, NC) for arm D and 5.8 months (95% CI: 5.6, NE) for arm F. At DCO, the median overall survival in both arms was not reached. Updated time matched safety and efficacy data will be provided at the time of presentation. Conclusion: The time matched analysis shows that lowering the dose of T-DXd to 5.4 mg/kg from 6.4 mg/kg and lowering the starting dose of capecitabine, did not result in decrease in efficacy of the combination of T-DXd + FP + pembrolizumab. Funding: This study is sponsored by AstraZeneca in collaboration with Daiichi Sankyo. In March 2019, AstraZeneca entered into a global development and commercialization collaboration agreement with Daiichi Sankyo for trastuzumab deruxtecan (T-DXd; DS-8201). Editorial acknowledgment: Under guidance of the authors and in accordance with Good Publication Practice, medical writing and editorial support was provided by Carmen Grimaldos, PhD, of Helios Medical Communications, part of Helios Global Group, and was funded by AstraZeneca. Clinical trial information: NCT04379596