LC-1-40 is a potent, specific NUDT1 (MTH1) degrader/PROTAC with DC50 of 0.97 nM in SHEP MYCN-ER cells, Dmax value of 96% at 50 nM.
LC-1-40 induced a dose- and time-dependent NUDT1 degradation in SHEP MYCN-ER cells.
LC-1-40 causes minimal changes in NUDT1 mRNA levels in Kelly and SF188 cells.
LC-1-40 markedly increases 8-oxo-dG levels and selectively induces SHEP cell death upon 4-OHT induction of MYCN hyperactivation, elicits MYC(N)-driven synthetic lethality
LC-1-40 (IP, 30 mg/kg) caused a remarkable intratumoral NUDT1 depletion within 1 h in patient-derived xenografts using MYCN-amplified T409 and MYCN-nonamplified T423 primary neuroblastoma tumors.
LC-1-40 (30 mg/kg) selectively impeded the growth of MYCN-amplified T409 tumors.
