Extended Data Fig. 4: AN15368 is activated by a T. cruzi serine carboxypeptidase and targets CPSF3. | Nature Microbiology

Extended Data Fig. 4: AN15368 is activated by a T. cruzi serine carboxypeptidase and targets CPSF3.

From: Discovery of an orally active benzoxaborole prodrug effective in the treatment of Chagas disease in non-human primates

Extended Data Fig. 4

a. Fold change in CPSF3 transcripts by qRT-PCR in two CPSF3-overexpressing T. cruzi lines (n = 3 biological replicates). b. Overexpression of CPSF3 in T. cruzi results in increased resistance to all AN15368 analogues (CSPF3-OE: n = 3 biological replicates; WT: n = 2 biological replicates). c. AN15368 analogues require activation by the T. cruzi CBP in order to efficiently kill intracellular T. cruzi as demonstrated by the increased resistance of CBP deficient parasites (TcCBP KO: n = 3 biological replicates; WT: n = 2 biological replicates). d. AN15368 analogues with poor activity against intracellular T. cruzi amastigotes have low nanomolar activity on extracellular amastigotes (n = 3 biological replicates). Data are presented as mean values + /- SD.

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