JOURNAL OF MEDICINAL CHEMISTRY药物化学杂志
JOURNAL OF MEDICINAL CHEMISTRY(英文缩写 J MED CHEM),ISSN 0022-2623,eISSN 1520-4804,中文译名:药物化学杂志 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-09-27 至 2026-09-27，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 8.039 | Q1 |
| 2022 | 7.300 | Q1 |
| 2023 | 6.800 | Q1 |
| 2024 | 6.800 | Q1 |
| 2025 | 7.300 | Q1 |
JOURNAL OF MEDICINAL CHEMISTRY 最新收录文献
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2. Retraction of "Redesigning Kinase Inhibitors to Enhance Specificity".
PMID:日期:2026-09-10该文献暂无摘要。
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3. Retraction of "A Priori Inference of Cross Reactivity for Drug-Targeted Kinases".
PMID:日期:2026-09-10该文献暂无摘要。
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4. A 177Lu-Labeled Circular Bivalent Aptamer for PTK7-Targeting Radionuclide Therapy in Ovarian Cancer and Orthotopic Hepatoblastoma.
PMID:日期:2026-09-10Targeted radionuclide therapy (TRT) is a promising strategy for precision oncology but is limited by the lack of high-performance targeting ligands. Here, we report a lutetium-177 (177Lu)-labeled PTK7-targeted cyclized bivalent aptamer (CBSgc8) for treating an orthotopic hepatoblastoma. The cyclized multivalent design enhances biostability and binding affinity, while 177Lu labeling preserves its functional properties. The resulting 177Lu-CBSgc8 exhibited high serum stability, strong specificity for PTK7-positive cells, efficient internalization, and dose-dependent cytotoxicity in vitro. In vivo, 177Lu-CBSgc8 inhibited tumor growth in an OVCAR3 ovarian cancer model, although tumor accumulation remained limited. Given its PTK7-targeting capability and preferential hepatic distribution, we further evaluated its therapeutic potential in an orthotopic HepG2 hepatoblastoma model. In this setting, 177Lu-CBSgc8 achieved 76.6% tumor growth inhibition with a favorable safety. These findings demonstrate the potential of exploiting tissue distribution characteristics together with molecular targeting to expand the applicability of aptamer-based TRTs.
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5. From Fragment Hit to Clinical Candidate: Discovery of Dual H1R/H4R Ligands with Superior Efficacy in Allergic Conjunctivitis.
PMID:日期:2026-09-10Dual inhibition of the histamine H1 and H4 receptors (H1R and H4R) has been shown to provide superior anti-inflammatory efficacy in preclinical models of allergic disease compared to selective inhibition of either receptor alone. Building on this concept, we initiated a fragment-based discovery program and previously identified a quinazoline-containing fragment hit. Here, we describe the lead optimization toward compounds with unique dual H1R/H4R activity. Structure-activity relationship studies yielded potent and balanced ligands with nanomolar affinities for both receptors, as well as pharmacokinetic properties suitable for ocular administration. Among these, quinazoline 35.HCl (GD136) and tetrahydroquinazoline 72.HCl (GD134) demonstrate robust in vivo efficacy in a ragweed-induced mouse model of allergic conjunctivitis, significantly reducing hyperemia and outperforming selective H1R or H4R antagonists. Based on its pharmacological profile, ADME properties, ease of formulation, and in vivo efficacy, GD134 was selected as the clinical development candidate for a first-in-class dual-targeted therapy of allergic conjunctivitis.
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6. Potent Anticancer Tethered Organorhodium(III) Complexes Target the Mitochondria.
PMID:日期:2026-09-10We report a family of tethered rhodium(III) complexes of formula [Rh(η5:κ1-C5Me4(CH2)npyN)(C,N)]+ (n = 1 or 2; C,N = 2-phenylpyridine or benzoquinoline), their nontethered analogues, and their iridium(III) counterparts. The tethered pyridine, κ1-coordinated to the metal, does not dissociate in water, yet the metal-Npy(tether) bond can be cleaved by strong nucleophiles, enabling metal activation. We corroborated that metal-Z bond reactivity correlated with cytotoxicity in breast cancer cells; complexes lacking reactive metal-Z bonds exhibited low anticancer potency, while excessive reactivity impaired efficacy likely through off-target reactions. For the highly potent tethered complexes, we determined the kinetics of pyridine cleavage using DMSO and confirmed that N-acetylcysteine can also promote pyridine dissociation. In tethered complexes, metal-mediated reactivity is crucial to potency, as metal-pyridine bonds with higher activation energy produce complexes less damaging to cells. We confirmed mitochondrial involvement in cell death, demonstrating that the most cytotoxic complexes inhibit OXPHOS more efficiently.
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7. Discovery of a Covalent NLRP3 LRR-Domain Probe: Reversing Renal Fibrosis via Immunometabolic Reprogramming in Organoid and Murine Models.
PMID:日期:2026-09-10Targeting the NLRP3 inflammasome is critical for treating fibrotic diseases; however, current NACHT domain inhibitors face mutational escape and limited isoform specificity. The autoinhibitory leucine-rich repeat (LRR) domain represents an underexplored pharmacological target. Here, we report QX-31, a novel covalent probe selectively engaging the LRR domain. QX-31 covalently binds to Cysteine 838, stabilizing NLRP3 in an inactive conformation and preventing inflammasome assembly with high selectivity over AIM2 and NLRC4. Furthermore, QX-31 reverses maladaptive immunometabolic reprogramming within the renal microenvironment by blunting the PI3K/AKT/HIF-1α axis, suppressing aberrant glycolysis and glutaminolysis. Evaluated in human kidney organoids and murine models of renal injury (UUO and IRI), QX-31 demonstrated potent antifibrotic efficacy comparable to reference drugs, alongside a favorable safety profile. Collectively, QX-31 serves as a valuable chemical tool, demonstrating that covalent targeting of this conformational regulatory domain is a viable therapeutic strategy for fibrotic diseases.
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8. Lead Optimization of Multimutant KRAS Switch-II Pocket Macrocyclic Inhibitors via Isosteric Replacement to Improve ADME and Oral Exposure.
PMID:日期:2026-09-10Starting from our internally discovered, potent panKRAS inhibitor BRSD-143 (1), we executed a targeted bioisosteric optimization of the naphthol and fluoropyrrolizidine motifs to preserve (or increase) KRAS pan-inhibitory potency while improving DMPK/ADME liabilities. These studies delivered 12 (BRSD-212), a highly potent and efficacious lead in which (2-azabicyclo[4.2.0]octan-6-yl)methanol (ABO) serves as a bioisostere for the widely deployed 2-fluoropyrrolizidine substituent. In parallel, replacement of the naphthol moiety with an indazole afforded 21, which demonstrated improved pharmacokinetic performance and ADME characteristics by mitigating glucuronidation-mediated clearance as the dominant metabolic pathway.
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9. Synthesis, Biological Evaluation, and Biodistribution of Xinyne, a Novel Quinazoline-carbazole N-methylamine Anticancer Agent Used in Mice Xenograft Models.
PMID:日期:2026-09-10Xinyne, a diaryl-N-methylamine analogue of isoCombretastatin A-4 was synthesized via a late-stage Cl-exchange using KCN. Xinyne exhibited potent antiproliferative activity at nanomolar concentrations against various human cancer cell lines, inhibited tubulin polymerization, induced apoptosis, and induced G2/M phase cell cycle arrest in 4T1 cells. To investigate its in vivo behavior, radiolabeled [14C]-Xinyne was prepared using [14C]-KCN. Pharmacokinetic analysis revealed significant sex-based differences: males showed faster absorption and more efficient elimination, whereas females exhibited broader tissue distribution and slower clearance. A biodistribution study demonstrated preferential accumulation of [14C]-Xinyne in the liver and the small intestine, with larger elimination through feces. Finally, the antitumor efficacy of Xinyne was confirmed in a murine breast cancer model.
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10. Design, Synthesis, and Antitumor Activity Evaluation of Novel Dual A2A/A2B Adenosine Receptor Antagonists.
PMID:日期:2026-09-10Adenosine is an essential signaling molecule with a well-recognized role in the central nervous, cardiovascular, and immune systems. Its immunosuppressive effects have gained significant attention in oncology, as adenosine accumulation within the tumor microenvironment can profoundly inhibit antitumor immunity. Therapeutic strategies to counteract this pathway include inhibiting adenosine-generating enzymes CD39 and CD73 or blocking adenosine A2A and A2B receptors. In this study, we report the development of compound 45, a novel imidazopyrazine derivative acting as a long-lasting, dual A2A/A2B receptor antagonist with nanomolar in vitro potency. This compound exhibits extended receptor residence time and maintains dual antagonistic activity even at high micromolar adenosine levels. Compound 45 demonstrates favorable ADME characteristics as well as pharmacokinetic properties, providing high oral bioavailability and systemic exposure across multiple preclinical species. In efficacy studies, this agent robustly reduced metastatic burden in a murine MCA205 pulmonary metastasis model.