Uses
MAP855 is a highly potent, selective, ATP-competitive and orally active MEK1/2 kinase inhibitor (MEK1 ERK2 cascade IC50=3 nM, pERK EC50=5 nM). MAP855 shows equipotent inhibition of wild-type and mutant MEK1/2[1].
Biological Activity
MAP855 is a highly potent, selective, ATP-competitive and orally active MEK1/2 kinase inhibitor (MEK1 ERK2 cascade IC50=3 nM, pERK EC50=5 nM). MAP855 shows equipotent inhibition of wild-type and mutant MEK1/2[1].
MAP855 (compound 30) has single-digit nM inhibition of pERK and proliferation in A375 cells (pERK EC50=5 nM)[1].
MAP855 (3 mg/kg for i.v., 10 mg/kg for p.o.; single) has good oral bioavailability and medium clearance in rodents[1].MAP855 (30 mg/kg; p.o., b.i.d, 14 days) achieves comparable efficacy to trametinib dosed at the mouse MTD without any body weight loss[1].Pharmacokinetic Parameters of MAP855 in mouse, rat and dog[1]. mouse rat dog CL [mL/min*kg]323522Vss [l/kg]2.62.01.8AUC po d.n. [μM*h]0.40.61.4 Oral BAV [% F]4465100
in vivo
MAP855 (3 mg/kg for i.v., 10 mg/kg for p.o.; single) has good oral bioavailability and medium clearance in rodents[1].
MAP855 (30 mg/kg; p.o., b.i.d, 14 days) achieves comparable efficacy to trametinib dosed at the mouse MTD without any body weight loss[1].
Pharmacokinetic Parameters of MAP855 in mouse, rat and dog[1].
| mouse | rat | dog |
| CL [mL/min*kg] | 32 | 35 | 22 |
| Vss [l/kg] | 2.6 | 2.0 | 1.8 |
| AUC po d.n. [μM*h] | 0.4 | 0.6 | 1.4 |
| Oral BAV [% F] | 44 | 65 | 100 |
| Animal Model: | Male Wistar Rats[1] |
| Dosage: | 3 mg/kg for i.v., 10 mg/kg for p.o. |
| Administration: | i.v. and p.o., single |
| Result: | Showed good oral bioavailability and medium clearance. |
| Animal Model: | A375 Tumor Bearing Mice[1] |
| Dosage: | 30 mg/kg |
| Administration: | p.o., b.i.d, 14 days |
| Result: | Achieved comparable efficacy to trametinib dosed at the mouse MTD without any body weight loss. |
IC 50
ERK: 5 nM (EC50); MEK1: 3 nM (IC50)
References
[1]. Poddutoori R, et al. Discovery of MAP855, an Efficacious and Selective MEK1/2 Inhibitor with an ATP-Competitive Mode of Action. J Med Chem. 2022;65(5):4350-4366.
