DDD85646

DDD85646 (IMP-366) is an orally active of trypanosoma brucei N-myristoyltransferase (TbNMT IC₅₀=2 nM; hNMT IC₅₀=4 nM). The enzyme N-myristoyltransferase (NMT) is a potential agent target for human African trypanosomiasis^[1][2][3][4]. In Vitro:DDD85646 (50 nM) female NMRI mouse model showed significant antitrypanosomic activity^[3].
DDD85646 (0-100 nM; 6, 24h) has a targeting effect in Trypanosoma brucei, and can effectively inhibit the N-myristyl transferase (TbNMT) of bloodstream type Trypanosoma Brucei, and this inhibition is directly related to the inhibition of proliferation of Trypanosoma Brucei^[3].
DDD85646 has an IC₅₀ value of 4.4 nM for L. donovani NMT and an EC₅₀ value of 8µM for L. donovani extracellular amastigotes^[3].
In Vivo:DDD85646 (10, 50 mg/kg; Oral administration; 1) has moderate bioavailability (about 20%) in female NMRI mouse models, and the free drug level is higher than EC₉₉ (EC₉₉ is about 6 nM), which can effectively inhibit the proliferation of T. b. brucei^[3].
DDD85646 (0-50 mg/kg; Oral administration; Twice a day; 4 days) kills Trypanosoma brucei by acting on TbNMT in T. b. brucei acute mouse model of HAT^[3].
DDD85646 (50 mg/kg; Oral administration; Twice a day) shows significant antitrypanosomic activity in female NMRI mice models^[3].