PD 198306

PD 198306 is a selective MAPK/ERK-kinase (MEK) inhibitor. PD 198306 results in an observable reduction in the Streptozocin induced increase in the level of active ERK1 and 2. Antihyperalgesic effects[1].

Signaling Pathways >> MAPK/ERK Pathway >> MEK

Research Areas >> Neurological Disease

MEK

PD198306 significantly inhibits Tha-GFP replication by 25% at 10 μM, after 36 h[2]. PD198306 (5 μM) reduces Tha-Crimson replication significantly by 20% at 18 h but such a result could not be confirmed at 36 h[2]. Cell Cycle Analysis[2] Cell Line: Human induced pluripotent stem cells (iPSC) Concentration: 10  μM Incubation Time: 6  hours Result: Inhibited Tha-Crimson replication at 10 μM, reducing it by 30% at 18 h and 50% at 36 h.

Intrathecal administration of PD 198306 (1-30 μg per 10 μL) dose-dependently (1-30 μg) blocks static allodynia in both the streptozocin and the chronic constriction injury (CCI) models of neuropathic pain[1]. Animal Model: Male Sprague Dawley rats (250-300 g) bearing neuropathic pain[1] Dosage: 1-30 μg per 10 μL and 3 mg per 100 μL (PD 198306 is suspended in cremophor:ethanol:water, 1 : 1 : 8.) Administration: Single doses of intrathecal (i.t.) or intraplantar (ipl) of PD 198306 (1-30 μg per 10 μL and 3 mg per 100 μL respectively Result: Intrathecal administration dose-dependently (1-30 μg) blocked static allodynia the streptozocin model of neuropathic pain. The minimum effective doses (MED) of 3 μg significantly blocked static allodynia 30 min after treatment. Both 10 μg and the highest dose used (30 μg) totally blocked the maintenance of static allodynia, for up to 1 h.

[1]. A Ciruela, et al. Identification of MEK1 as a novel target for the treatment of neuropathic pain. Br J Pharmacol. 2003 Mar;138(5):751-6.

[2]. Benoit Besson, et al. Kinome-Wide RNA Interference Screening Identifies Mitogen-Activated Protein Kinases and Phosphatidylinositol Metabolism as Key Factors for Rabies Virus Infection. mSphere. 2019 May 22;4(3):e00047-19.