MAP855

• CAT Number: I043857
• CAS Number: 1660107-77-6
• Molecular Formula: C28H23ClF2N6O3
• Molecular Weight: 564.97
• Purity: ≥95%
• Synonyms: 1-[(3S,4S)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone
• InChI: InChI=1S/C28H23ClF2N6O3/c1-15-35-24-12-34-23-11-21(30)18(17-4-3-16(9-20(17)29)40-28-32-6-2-7-33-28)10-19(23)27(24)37(15)25-5-8-36(13-22(25)31)26(39)14-38/h2-4,6-7,9-12,22,25,38H,5,8,13-14H2,1H3/t22-,25-/m0/s1
• InChIKey: WZZBNLYBHUDSHF-DHLKQENFSA-N
• SMILES: CC1=NC2=C(N1C3CCN(CC3F)C(=O)CO)C4=CC(=C(C=C4N=C2)F)C5=C(C=C(C=C5)OC6=NC=CC=N6)Cl

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]
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

Reference

[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.
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