EGR240 (ERG240) is an orally active, selective inhibitor of branched-chain amino acid transaminase 1 (BCAT1) with an IC₅₀ of 0.1–1nM[1-2]. EGR240 is suitable for research in cancer, rheumatoid arthritis, and bone diseases[3-4].
In vitro, THP-1 macrophages were pretreated with EGR240 (20μM) for 3 hours, followed by LPS (200ng/mL) and Nigericin (10μM) to induce pyroptosis. EGR240 significantly suppressed BCAT1-mediated NF-κB signaling activation and reduced the secretion of key pyroptosis-related proteins, GSDMD-NT and IL-1β[5]. Ovarian cancer persistent cells (OVCAR8-Persister and A2780-Persister) were treated with EGR240 (60μM) for 24 hours. EGR240 did not significantly affect cell viability, and EGR240 combination with paclitaxel did not enhance paclitaxel cytotoxicity[6].
In vivo, collagen-induced arthritis mice were orally administered EGR240 (720–1000mg/kg). EGR240 significantly alleviated arthritis severity, reducing joint inflammation, pannus formation, cartilage degradation, and bone erosion[7]. db/db diabetic retinopathy mice received intravitreal injections of EGR240 (100–200μM; 1μL) for 2 or 4 weeks. EGR240 significantly downregulated retinal inflammatory gene mRNA expression, such as Gfap and Il6, and reduced retinal vascular leakage[8].
References:
[1] Papathanassiu, et al. Methods for treatment of cancer, inflammatory autoimmune disorders and bone diseases using branched-chain amino acid aminotransferase-1 (BCAT1) inhibitors. Patent. WO2012173987.
[2] Angana A.H, Jozefina Dzanan, Ali, et al. Aging promotes lung cancer metastasis through epigenetic ATF4 induction. bioRxiv 2024.07.03.601209.
[3] Chen L, Shi Y, Xiao D, et al. NR4A1 deficiency promotes carotid plaque vulnerability by activating integrated stress response via targeting Bcat1. Cell Mol Life Sci. 2025 Feb 22;82(1):91.
[4] Yuan Z, Li M, Tang Z. BCAT1 promotes cell proliferation, migration, and invasion via the PI3K-Akt signaling pathway in oral squamous cell carcinoma. Oral Dis. 2025 Feb;31(2):364-375.
[5] Feng J, Zhang H, Zhu M, et al. CHI3L1 promotes macrophage pyroptosis in ulcerative colitis via the BCAT1/NF-κB axis. Life Sci. 2026 Jan 1;384:124108.
[6] Lin H, Wang L, Chen H, et al. Mitochondrial fatty acid oxidation as the target for blocking therapy-resistance and inhibiting tumor recurrence: The proof-of-principle model demonstrated for ovarian cancer cells. J Adv Res. 2026 Jan;79:571-585.
[7] Papathanassiu AE, Ko JH, Imprialou M, et al. BCAT1 controls metabolic reprogramming in activated human macrophages and is associated with inflammatory diseases. Nat Commun. 2017 Jul 12;8:16040.
[8] Wang J, Yin Z, Yang J, et al. BCAT1 Activation Reprograms Branched-Chain Amino Acid Metabolism and Epigenetically Promotes Inflammation in Diabetic Retinopathy. Invest Ophthalmol Vis Sci. 2025 Jun 2;66(6):59.
EGR240 (ERG240)是一种具有口服活性的支链氨基酸转氨酶1（BCAT1）选择性抑制剂（IC₅₀=0.1-1nM）[1-2]。EGR240可用于癌症、类风湿性关节炎及骨病的相关研究[3-4]。
在体外，EGR240（20μM）预处理THP-1巨噬细胞3小时，随后在LPS（200ng/mL）和Nigericin（10μM）诱导的焦亡模型中，EGR240显著抑制BCAT1介导的NF-κB信号通路活化，并降低焦亡关键蛋白GSDMD-NT和IL-1β的分泌[5]。EGR240（60μM）处理卵巢癌耐受细胞（OVCAR8-Persister和A2780-Persister）24小时，EGR240未显著影响细胞存活率。EGR240联合紫杉醇处理后未增强紫杉醇的细胞毒性[6]。
在体内，EGR240（720–1000mg/kg）口服给药处理胶原诱导关节炎小鼠，EGR240显著减轻关节炎严重程度，减少关节炎症、血管翳形成、软骨降解和骨侵蚀[7]。EGR240（100–200μM；1μL）玻璃体内注射处理db/db糖尿病视网膜病变小鼠2周或4周。EGR240显著降低视网膜中Gfap和Il6等炎症基因mRNA表达，并减轻视网膜血管渗漏[8]。