ADT-007 is a potent and orally active pan-RAS inhibitor with strong anticancer effects. ADT-007 binds RAS in a nucleotide-free conformation to block GTP activation. ADT-007 potently and selectively inhibits the growth of cancer cells with mutated or per-activated wild-type RAS isozymes.
ADT-007 displays the highest potency and selectivity to inhibit the growth of KRASG13D HCT-116 cells with an IC50 of 5 nM, while RAS 110 wild-type HT-29 cells are ~100 fold less sensitive with an IC50 of 493 nM. ADT-007 displays even greater potency in KRAS G12C MIA PaCa-2 PDA cells, resulting in IC50 values as low as 2 nM. ADT-007 also potently inhibits the growth of three other mutant KRAS PDA cell lines with G12V or G12D mutations[1].
ADT-007 (10 mg/kg; intra-tumoral injection; once a day; for 17-21 days) strongly inhibits tumor growth in syngeneic immune competent mouse models of colorectal cancer[1].
References:
[1]. Jeremy B Foote, et al. A Novel Pan-RAS Inhibitor with a Unique Mechanism of Action Blocks Tumor Growth in Mouse Models of GI Cancer. bioRxiv[Preprint]. 2024 Jan 24:2023.05.17.541233.