molecules of the month


>300-fold family-selective PARP14 inh. tool

90x IC50 coverage at 500 mpk BID PO in vivo

from PARP-preferring directed library + SBDD

Cell Chem. Bio., Mar. 10, 2021

Ribon Therapeutics, Cambridge, MA

1 min read

The Ribon Therapeutics PARP14 inhibitor (RBN-012759) is a tool compound with >300x selectivity over all PARP family members. While PARP1/2 are well-known to drug hunters as synthetic lethal targets due to their role in DNA damage repair, there are 17 PARP enzymes with many other biological roles without as much pharmacological exploration. The starting point for RBN-012759 was identified by screening a PARP-preferring directed library and structure-based design led to RBN-012759. Preclinical studies in mice demonstrated modest oral bioavailability of RBN-012759, but it was well tolerated over several days at 500 mg/kg BID orally, a dose that provides 90-fold coverage of the mouse PARP14-free IC50 value (15 ng/mL) at 8 h. This tool should help elucidate the role of PARP14…

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