Indoximod  别名：NLG-8189; D1MT; 1-methyl-D-tryptophan; 吲哚莫德

Indoximod (别名D-1MT, NLG8189) 是一种吲哚胺2,3-双加氧酶 (IDO) 通路的抑制剂，其Ki值为19 μM。Indoximod 是一种可用于癌症研究的免疫代谢佐剂。Indoximod激活Trp充足信号而刺激mTOR，并解除IDO诱导的Trp缺乏和自体吞噬响应。Indoximod (D-1MT, NLG8189)以两种具有潜在不同生物学特性的立体异构体存在。L异构体是在纯化酶和基于HeLa细胞的测定中更有效的IDO活性抑制剂。而D异构体在逆转由表达IDO的树突细胞产生的T细胞的抑制方面显得更为有效。

体内研究中，口服联合给予dl-1-methyl-tryptophan与紫杉醇，可引起原发性乳腺肿瘤的消退。在移植的黑色素瘤和移植的原生乳腺癌小鼠模型中，Indoximod (400 mg/kg p.o.) 结合化学免疫疗法增强抗肿瘤免疫力。

To prepare 1MT for oral gavage, 1 g of 1MT was added to a 15 ml conical tube with 7.8 ml Methocel/Tween [0.5% Tween 80/0.5% Methylcellulose (v/v in water)]. The mixture was bead milled overnight by adding 1-2 ml by volume of 3 mm glass beads (Fisher) and mixing by inversion. The next day, the 1MT concentration was adjusted to 85 mg/ml by adding an additional 4 ml Methocel/Tween and mixing again briefly. The 1MT slurry was administered by oral gavage at 400 mg/kg/dose (0.1 cc/20 g mouse) using a curved feeding needle (20 G x 1 1/2 in; Fisher). For bid (twice a day) dosing, 1MT was administered once in the morning and once in the evening.

For administration in drinking water, D-1MT was prepared at 2 mg/ml in water as described above, supplemented with a small amount of aspartame (2 envelopes per liter) to improve acceptance by the mice, and filter sterilized. The solution was delivered in standard autoclaved drinking-water bottles. Mice drank 4.5-5.0 ml/day (similar to consumption of water without drug).