M-808 is a highly potent and efficacious covalent Menin-MLL interaction inhibitor, with a binding IC50 value of 2.6 nM [1].
In Vivo, M-808 (16) is well tolerated in severe combined immunodeficiency (SCID) mice with intravenous administration of 10 mg/kg (or 25 mg/kg) every other day dosing (three times a week) for one week. M-808 (25 mg/kg) achieves a maximum tumor growth inhibition (TGI) of 97% during treatment (day 35) and reduces the average tumor volume from 92 mm3 at the beginning of the treatment to 59 mm3 at day 35, with no significant toxicity[1].
In Vitro, M808 exhibits IC50 values of 1 nM, 4 nM and 2.8 nM in MV4;11 cells, MOLM-13 cells and HL60 cells, respectively[1]. M808 forms a covalent bond between its acrylamide and the sulfur atom of Cys329 in menin[1].
References:
[1]. Shilin Xu, et al. Discovery of M-808 as a Highly Potent, Covalent, Small-Molecule Inhibitor of the Menin-MLL Interaction With Strong In Vivo Antitumor Activity. J Med Chem. 2020 May 14;63(9):4997-5010.
In Vivo, M-808 (16) is well tolerated in severe combined immunodeficiency (SCID) mice with intravenous administration of 10 mg/kg (or 25 mg/kg) every other day dosing (three times a week) for one week. M-808 (25 mg/kg) achieves a maximum tumor growth inhibition (TGI) of 97% during treatment (day 35) and reduces the average tumor volume from 92 mm3 at the beginning of the treatment to 59 mm3 at day 35, with no significant toxicity[1].
In Vitro, M808 exhibits IC50 values of 1 nM, 4 nM and 2.8 nM in MV4;11 cells, MOLM-13 cells and HL60 cells, respectively[1]. M808 forms a covalent bond between its acrylamide and the sulfur atom of Cys329 in menin[1].
References:
[1]. Shilin Xu, et al. Discovery of M-808 as a Highly Potent, Covalent, Small-Molecule Inhibitor of the Menin-MLL Interaction With Strong In Vivo Antitumor Activity. J Med Chem. 2020 May 14;63(9):4997-5010.