TNG260 (TNG-260) is a potent, CoREST-selective deacetylase (CoreDAC) inhibitor, inhibits HDAC1 with 10-fold selectivity over HDAC3 in cells.
TNG260 displays 500-fold selectivity for the CoREST complex over the other HDAC1-containing complexes, NuRD and Sin3.
TNG260 re-sensitizes α-PD1 resistant STK11-mutant MC38 syngeneic tumor model with α-PD1.
The combination of TNG260 and α-PD1 led to durable complete tumor regressions in α-PD1 resistant STK11-mutant MC38 syngeneic tumor models.
TNG260 has no anti-tumor efficacy in immunocompromised mice, indicating the tumor cell killing with TNG260 is immune-mediated and not due to direct cell killing.
TNG260 also decreased intratumoral infiltration of neutrophils, an immune suppressive cell type associated with STK11-mutant NSCLC.
TNG260 reverses the immune evasion phenotype caused by loss of STK11 and induces tumor regressions in an STK11-mutant model in combination with α-PD1.