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BCH001, a quinoline derivative, is a specific PAPD5 inhibitor. BCH001 restores telomerase activity and telomere length in dyskeratosis congenita (DC) induced pluripotent stem cells. BCH001 shows no inhibition of poly(A)-specific ribonuclease (PARN) or several other canonical and non-canonical polynucleotide polymerases. BCH001 is used to regulate aging.

BCH001 (100 nM-1 µM; for 7 days) reduces telomerase RNA component (TERC) RNA oligo-adenylation and increases steady state TERC RNA levels in PARN-mutant iPSC clones. BCH001 causes few transcriptome-wide changes and rescues other ncRNAs disrupted by PARN mutations.
BCH001 (1 µM, 24-72 h) has no adverse impact on cell growth, cell cycle, or apoptosis in induced pluripotent stem cells (iPSCs) from DC.
BCH001 inhibits ATP- and dose-dependently recombinant PAPD5 (rPAPD5) in vitro. PAPD5 is a non-canonical polymerase that oligoadenylates and destabilizes telomerase RNA component (TERC).

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