BCH001 (BCH-001) a specific, small molecule PAPD5 inhibitor, inhibits rPAPD5 in the low micromolar range in vitro.
BCH001 showed no inhibition of PARN or several other canonical and non-canonical polynucleotide polymerases.
BCH001 exhibited ATP- and dose-dependent binding to rPAPD5.
BCH001 (0.1-1 uM) restores TERC and telomere length in dyskeratosis congenita (DC) patient iPSCs, reversibly normalizes telomere length and non-coding RNA biogenesis.
BCH001 upregulates TERC without immortalizing TERT-negative cells, restores TERC maturation in PARN-deficient primary human HSPCs and leukemia cell lines.
