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在落幕的 ACS Spring 2025 (美國化學會春季年會) 上，多個創新藥物首-次披露，涵蓋了腫瘤、心血管、神經系統疾病等多個領域。

這些小分子藥物代表了當下最-前沿的藥物化學設計趨勢。這些首-次亮相的“新星"是否有望成為下一代重磅新藥？跟隨小 M 一起來看看它們的背景信息。

這 12 個首-次亮相的小分子藥物，不僅展示了目前藥物研發的多樣化方向 (從傳統抑制劑到蛋白降解劑、共價靶向劑、大環肽等)，也反映出精準醫療背景下對突變蛋白、腫瘤微環境、腦部靶點等復雜機制的深入探索。部分分子已經進入臨床階段，值得持續關注。

[1] Seth Cohen, et al. First disclosure of FG-2101: A novel non-hydroxamate inhibitor of LpxC for treating Gram-negative bacteria infections including drug-resistant strains. ACS. 2025 Mar 26.

[2] Koichi Ito, et al. Abstract B113: Discovery of PRT3789, a first-in-class potent and selective SMARCA2 degrader in clinical trials for the treatment of patients with SMARCA4 mutated cancers. Mol Cancer Ther 1 December 2023; 22 (12_Supplement): B113. 

[3] Lynda Groocock, et al. BMS-986458 a Potential First-in-Class, Highly Selective, Potent and Well Tolerated BCL6 Ligand Directed Degrader (LDD) Demonstrates Multi-Modal Anti-Tumor Efficacy for the Treatment of B-Cell Non-Hodgkin's Lymphoma. Blood. 2024 Volume 144, Supplement 1, Page 957.

[4] Frederic Vallee. Discovery of RP-1664 / a first-in-class orally bioavailable, selective PLK4 inhibitor. ACS. 2025 Mar 26.

[5] Paul M. Scola, et al. Discovery of BMS-986238, a second-generation macrocyclic peptide inhibitor of programmed death-ligand 1 (PD-L1). ACS. 2025 Mar 26.

[6] Yee B, et al. O013 Preliminary Results from a Phase 1 Study of ALKS 2680, an Orexin-2 receptor Agonist, in Healthy Participants and Patients with Narcolepsy or Idiopathic Hypersomnia. Sleep Adv. 2023 Oct 23;4(Suppl 1):A5–6.

[7] Marco Borgogno, et al. Discovery of IAMA-6: A selective inhibitor of NKCC1 and clinical candidate to treat brain disorders. ACS. 2025 Mar 26.

[8] Hong, M.H, et al. A global phase 1b study of ORIC-114, a highly selective, brain penetrant EGFR and HER2 inhibitor, in patients with advanced solid tumors harboring EGFR Exon 20 or HER2 alterations. Annals of Oncology, Volume 34, S769.

[9] Anneli Nordqvist, et al. AZD2389, a first in class candidate drug for the treatment of metabolic dysfunction-associated steatohepatitis. ACS. 2025 Mar 26.

[10] Thomas Chappie, et al. PF-07853578: A clinical candidate for the treatment of PNPLA3 I148M mediated MASLD. ACS. 2025 Mar 26.

[11] Sankar Sarkar, et al. Preclinical characterization of CK-4021586, a new class of cardiac myosin inhibitors for the treatment of hypertrophic cardiomyopathy. Biophysical Journal, Volume 122, Issue 3, 122a.

[12] Robert Silasi, et al. Treatment with a Novel Small Molecule Dual Factor IIa/Xa Inhibitor Protects Against Coagulopathy and Organ Dysfunction in a Baboon Model of Staphylococcus Aureus Sepsis. Blood. 2024 Volume 144, Supplement 1, Page 3988.