Indoleamine 2,3-dioxygenase 1 (IDO1) is a cytosolic enzyme involved in immune metabolism and inflammatory programing via the regulation in tryptophan catabolism. BMS-986205 is a selective, irreversible inhibitor of IDO1 that potently inhibits kynurenine production in IDO1-HEK293 cells with an IC50 value of 1.1 nM[3]. BMS-986205 also displayed inhibitory effect on IDO1 in Hela cells with an IC50 value of 0.5 nM[4]. In IFNγ SKOV-3 cells, BMS-98620 exhibited 80% maximum inhibition on IDO1 activity with an IC50 value of 9.5nM. IDO1-mediated blockage of Jurkat T cell activation was rescued by BMS-986205 with an IC50 value of 8nM. Incubation with BMS-98620 for 72 hours also induced Jurkar cell death with an IC50 value of 6.3M[5].
Linrodostat 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
SKOV3 xenograft model
Oral
60 mpk QD PO
Once daily
Evaluate the pharmacodynamic effects of Linrodostat on kynurenine levels in the SKOV3 xenograft model
ACS Med Chem Lett. 2021 Jan 28;12(2):288-294
Mice
B16F10 melanoma model
Intraperitoneal injection
10 mg/kg/day
Daily until the end of the experiment
To test the effect of varying doses of Linrodostat in combination with ibrutinib on tumor growth, and found that the dose of Linrodostat correlated with anti-tumor efficacy and induction of Ly6c+CD103+ DCs.
Immunity. 2021 Oct 12;54(10):2354-2371. e8
Mice
VPA-exposed pregnant mouse model
Subcutaneous injection
5 mg/kg
Single administration
Linrodostat inhibited placental IDO-1 expression and reversed the protective effects of taprenepag on maternal-fetal interface homeostasis.
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