Pan-RAS-IN-1 is cytostatic, possibly due to pan-RAS inhibition at some concentrations. Pan-RAS-IN-1 is evaluated in primary T cell acute lymphoblastic leukemia (T-ALL) cells. Selective lethality is observed, with mutant NRAS cells retaining only 20%-40% viability after 5 μM treatment. Pan-RAS-IN-1 binds to KRasG12D-GppNHp with an affinity of less than 20 μM. Pan-RAS-IN-1 binds to Ras proteins and exhibits lethality in cells partially dependent on the expression of Ras proteins. The potency of pan-RAS-IN-1 correlates with the degree of dependency on the mutated isoform over a 5-fold concentration range [1].

Pan-RAS-IN-1-treated mice show decreased tumor pERK levels compared with vehicle-treated mice. Pan-RAS-IN-1 administration causes inhibition of tumor growth over 15 days of treatment. A modest increase in cleaved caspase-3 is also observed, showing that pan-RAS-IN-1 has the capacity to induce caspase activation in this model[1].