| Identification | Back Directory | [Name]
Ethanone, 1-[(3S,4S)-4-[8-[2-chloro-4-(2-pyrimidinyloxy)phenyl]-7-fluoro-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl]-3-fluoro-1-piperidinyl]-2-hydroxy- | [CAS]
1660107-77-6 | [Synonyms]
MAP855
Ethanone, 1-[(3S,4S)-4-[8-[2-chloro-4-(2-pyrimidinyloxy)phenyl]-7-fluoro-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl]-3-fluoro-1-piperidinyl]-2-hydroxy- | [Molecular Formula]
C28H23ClF2N6O3 | [MOL File]
1660107-77-6.mol | [Molecular Weight]
564.97 |
| Chemical Properties | Back Directory | [Boiling point ]
813.9±75.0 °C(Predicted) | [density ]
1.53±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 100 mg/mL (177.00 mM; Need ultrasonic) | [form ]
Solid | [pka]
13.88±0.10(Predicted) | [color ]
Off-white to light yellow |
| Hazard Information | Back Directory | [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) | [storage]
Store at -20°C | [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. |
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