LM10 is an orally available, aqueous soluble, potent, selective and non-toxic tryptophan 2,3-dioxygenase (TDO) inhibitor. LM10 diminishes tryptophan degradation and effectively prevents the growth of TDO-expressing P815 tumor cells by reversing immune resistance in immune competent but not in immunodeficient mice (at a dose of 4 mg/day, 1 mg/ml in water, pH 9.0). LM10 suppresses autoimmune reactions induced by mouse hepatitis virus in mice.
Proceedings of the National Academy of Sciences of the United States of America, 109(7), 2497-2502 (2012-02-07)
Tryptophan catabolism mediated by indoleamine 2,3-dioxygenase (IDO1) is an important mechanism of peripheral immune tolerance contributing to tumoral immune resistance, and IDO1 inhibition is an active area of drug development. Tryptophan 2,3-dioxygenase (TDO) is an unrelated hepatic enzyme that also
Medical hypotheses, 131, 109314-109314 (2019-08-25)
Metabolic targeting of liver 5-aminolevulinate synthase (5-ALAS) by inhibition of heme utilisation by tryptophan (Trp) 2,3-dioxygenase (TDO) or the use of tryptophan is proposed as a therapy of acute hepatic porphyrias. 5-ALAS, the rate-limiting enzyme of heme biosynthesis, is under
In a previous work we demonstrated that inhibition of mouse indoleamine 2,3-dioxygenase (IDO) by methyltryptophan (MT) exacerbated the pathological actions of mouse hepatitis virus (MHV-A59) infection, suggesting that tryptophan (TRP) catabolism was involved in viral effects. Since there is a
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