ANA 12 is a small molecule, non-competitive, and highly selective TrkB receptor antagonist (high-affinity site: IC50 = 45.6nM; low-affinity site: IC50 = 41.1μM) [1]. ANA 12 blocks BDNF activation by binding to both high- and low-affinity sites of TrkB, thereby inhibiting multiple downstream signaling pathways (such as ERK/MAPK and PI3K), modulating neuroplasticity and behavior [2-3]. ANA 12 is primarily used to improve anxiety and depression-like symptoms [4].
In D283 and UW-228 cells, ANA 12 (5-30μM; 24-72h) selectively inhibits TrkB and suppresses the proliferation and viability of human cells [5]. In Schwann cells (SC) and B4B8 cells, ANA 12 (5μM; 4d) treatment reduced the mutual migration between SC and cancer cells and initiated more SC-associated cancer cell dissemination [6]. In SubG1 cells, ANA-12 (1μM; 24h) abolished the protective effect of brain-derived neurotrophic factor on astrocyte death induced by serum deprivation by increasing the percentage of SubG1 cells [7].
In C57BL/6 mouse, ANA 12 (0.5mg/kg; ip; 5d) treatment reduces ovarian volume and antral follicle number and increases the proportion of abnormal oocytes in 8-10 weeks-old mice [8]. In collagen-induced arthritis (CIA) mouse model, ANA 12 (0.5mg/kg; ip; 6d) treatment reduces pain behaviors and promotes motor function recovery [9].
References:
[1]. Cazorla M, Premont J, Mann A, et al. Identification of a low–molecular weight TrkB antagonist with anxiolytic and antidepressant activity in mice[J]. The Journal of clinical investigation, 2011, 121(5): 1846-1857.
[2]. Fang X, Yang C, Li S, et al. Brain-derived neurotrophic factor-TrkB signaling in the medial prefrontal cortex plays a role in the anhedonia-like phenotype after spared nerve injury[J]. European archives of psychiatry and clinical neuroscience, 2020, 270(2): 195-205.
[3]. Vassoler F M, White S L, Schmidt H D, et al. Epigenetic inheritance of a cocaine-resistance phenotype[J]. Nature neuroscience, 2013, 16(1): 42-47.
[4]. Zhang J, Yao W, Dong C, et al. Comparison of ketamine, 7, 8-dihydroxyflavone, and ANA-12 antidepressant effects in the social defeat stress model of depression[J]. Psychopharmacology, 2015, 232(23): 4325-4335.
[5]. Thomaz A, Pinheiro K V, Souza B K, et al. Antitumor activities and cellular changes induced by TrkB inhibition in medulloblastoma[J]. Frontiers in Pharmacology, 2019, 10: 698.
[6]. Ein L, Mei C, Bracho O, et al. Modulation of BDNF–TRKB interactions on Schwann cell-induced oral squamous cell carcinoma dispersion in vitro[J]. Anticancer research, 2019, 39(11): 5933-5942.
[7]. Saba J, Turati J, Ramirez D, et al. Astrocyte truncated-TrkB mediates BDNF antiapoptotic effect leading to neuroprotection[J]. J Neurochem, 2018, 146: 686-702.
[8]. Liu B, Liu Y, Li S, et al. BDNF promotes mouse follicular development and reverses ovarian aging by promoting cell proliferation[J]. Journal of Ovarian Research, 2023, 16(1): 83.
[9]. Yuan M, Zhang L, Zheng Y, et al. ANA-12 Targets and Inhibits BDNF/TrkB Signaling to Alleviate Pain Behaviors in Rheumatoid Arthritis Mice[J]. Neurochemical Research, 2025, 50(4): 1-14.
ANA 12是一种小分子、非竞争性、高选择性TrkB受体拮抗剂（高亲和力位点：IC50 = 45.6nM；低亲和力位点：IC50 = 41.1μM） [1]。ANA 12通过结合TrkB的高亲和力位点和低亲和力位点来阻断BDNF活化，从而抑制多条下游信号通路（例如ERK/MAPK和PI3K），调节神经可塑性和行为 [2-3]。ANA 12主要用于改善焦虑和抑郁样症状 [4]。
在D283和UW-228细胞中，ANA 12（5-30μM；24-72h）选择性抑制TrkB，并抑制人类细胞的增殖和活力 [5]。在Schwann细胞（SC）和B4B8细胞中，ANA 12（5μM；4d）治疗可降低SC细胞与癌细胞之间的相互迁移，并启动更多SC细胞相关的癌细胞播散 [6]。在SubG1细胞中，ANA-12（1μM；24h）通过增加SubG1细胞的百分比，消除了脑源性神经营养因子对serum deprivation诱导的星形胶质细胞死亡的保护作用 [7]。
在C57BL/6小鼠中，ANA 12（0.5mg/kg；ip；5d）治疗可减少8-10周龄小鼠的卵巢体积和窦卵泡数量，并增加异常卵母细胞的比例 [8]。在胶原诱导性关节炎（CIA）小鼠模型中，ANA 12（0.5mg/kg；ip；6d）治疗可减轻疼痛行为并促进运动功能恢复 [9]。