PD184161

PD184161 is an orally active MEK inhibitor. PD184161 inhibits MEK activity (IC50=10-100 nM) in a time- and concentration-dependent manner. PD184161 inhibits cell proliferation and induces apoptosis. PD184161 produces depressive-like behavior[1][2].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> MAPK/ERK Pathway >> MEK

Research Areas >> Neurological Disease

MEK:10-100 nM (IC50)

PD184161 (1-20 μM; 24, 48, or 72 hours) inhibits cell proliferation and induces apoptosis in a time and concentration dependent manner[1]. PD184161 (0.1 and 1.0 μM; 1 hour) inhibits ERK1,2 phosphorylation[1]. PD184161 (5 μM; 30 min) prevents the toxic effects of bicuculline[3]. Cell Proliferation Assay[1] Cell Line: HCC cell lines (HepG2, Hep3B, PLC, and SKHep) Concentration: 1-20 μM Incubation Time: 24, 48, or 72 hours Result: Inhibited cell proliferation. Apoptosis Analysis[1] Cell Line: HCC cell lines (HepG2, Hep3B, PLC, and SKHep) Concentration: 1-20 μM Incubation Time: 48 hours Result: Induced cell apoptosis. Western Blot Analysis[1] Cell Line: HCC cell lines (HepG2, Hep3B, PLC, and SKHep) Concentration: 0.1 and 1.0 μM Incubation Time: 1 hours Result: Inhibited ERK1,2 phosphorylation. Cell Viability Assay[3] Cell Line: Primary mouse neurons Concentration: 5 μM Incubation Time: 30 min Result: Prevents the toxic effects of bicuculline.

PD184161 reduces tumor xenograft P-ERK levels in 3-12 hours after an oral dose[1]. PD184161 (300 mg/kg; orogastric gavage twice daily for 38 days) significantly suppresses tumor engraftment and initial growth[1]. PD184161 (30 mg/kg; i.p.; single injection) produces depressive-like behavior[2]. PD184161 (500 μg/kg; intravenous injection) prevents the progression of neurological deficits and brain damage after stroke[3]. Animal Model: Hep3B tumor xenografts BALB/c athymic nude mice[1] Dosage: 300 mg/kg Administration: Orogastric gavage twice daily for 38 days Result: Decreased the early tumor growth. Animal Model: Male, 6 weeks C57Bl/6 mice[2] Dosage: 500 μg/kg Administration: intravenously in 30 min before MCAO or PTZ administration Result: Prevented the progression of neurological deficits and brain damage after stroke. Animal Model: C57Bl/6 mice[3] Dosage: 30 mg/kg Administration: i.p., single injection Result: Produced depressive-like behavior.

[1]. Klein PJ, et al. The effects of a novel MEK inhibitor PD184161 on MEK-ERK signaling and growth in human liver cancer. Neoplasia. 2006 Jan;8(1):1-8.

[2]. Duman CH, et al. A role for MAP kinase signaling in behavioral models of depression and antidepressant treatment. Biol Psychiatry. 2007 Mar 1;61(5):661-70.

[3]. Gladbach A, et al. ERK inhibition with PD184161 mitigates brain damage in a mouse model of stroke. J Neural Transm (Vienna). 2014 May;121(5):543-7.