PD184161

Research use only, not for human use.

PD184161 is a novel, orally-active MEK inhibitor.

PD184161 is a novel, orally-active MEK inhibitor. PD184161 inhibited MEK activity (IC50 = 10-100 nM) in a time- and concentration-dependent manner.(In Vitro):PD184161 inhibited MEK activity (IC50 = 10-100 nM) in a time- and concentration-dependent manner more effectively than PD098059 or U0126. PD184161 inhibited cell proliferation and induced apoptosis at concentrations of > or = 1.0 microM in a time- and concentration-dependent manner. (In Vivo):In vivo, tumor xenograft P-ERK levels were significantly reduced 3 to 12 hours after an oral dose of PD184161 (P < .05). Contrarily, tumor xenograft P-ERK levels following long-term (24 days) daily dosing of PD184161 were refractory to this signaling effect. PD184161 significantly suppressed tumor engraftment and initial growth (P < .0001); however, established tumors were not significantly affected. In conclusion, PD184161 has antitumor effects in HCC in vivo that appear to correlate with suppression of MEK activity .

PD184161 (1-20 μM; 24, 48, or 72 hours) inhibits cell proliferation and induces apoptosis in a time and concentration dependent manner.PD184161 (0.1 and 1.0 μM; 1 hour) inhibits ERK1,2 phosphorylation.PD184161 (5 μM; 30 min) prevents the toxic effects of bicuculline. Cell Proliferation Assay 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 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 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 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.PD184161 (300 mg/kg; orogastric gavage twice daily for 38 days) significantly suppresses tumor engraftment and initial growth.PD184161 (30 mg/kg; i.p.; single injection) produces depressive-like behavior.PD184161 (500 μg/kg; intravenous injection) prevents the progression of neurological deficits and brain damage after stroke. Animal Model:Hep3B tumor xenografts BALB/c athymic nude miceDosage: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 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 Dosage:30 mg/kg Administration:i.p., single injection Result:Produced depressive-like behavior.

PD 184161

MAPK/ERK Signaling

MEK

NO Synthase

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212631-67-9

557.56

C17H13BrClF2IN2O2

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (179.35 mM)

Fc1c(F)c(Nc2ccc(I)cc2Cl)c(cc1Br)C(=O)NOCC1CC1

——

(-20℃)

With Ice Pack

≥ 2 years