PD184161 is an orally bioactive, time- and concentration-dependent MEK inhibitor (IC50=10-100 nM). PD184161 inhibits cell growth/proliferation and causes apoptosis. PD184161 induces depressive-like behavior.

Physicochemical Properties

Molecular Formula	C17H13BRCLF2IN2O2
Molecular Weight	557.55
Exact Mass	555.886
CAS #	212631-67-9
PubChem CID	9937619
Appearance	Off-white to gray solid powder
Density	1.9±0.1 g/cm3
Index of Refraction	1.670
LogP	9.28
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	6
Heavy Atom Count	26
Complexity	505
Defined Atom Stereocenter Count	0
InChi Key	VJNZMSLGVUSPCF-UHFFFAOYSA-N
InChi Code	InChI=1S/C17H13BrClF2IN2O2/c18-11-6-10(17(25)24-26-7-8-1-2-8)16(15(21)14(11)20)23-13-4-3-9(22)5-12(13)19/h3-6,8,23H,1-2,7H2,(H,24,25)
Chemical Name	5-bromo-2-(2-chloro-4-iodoanilino)-N-(cyclopropylmethoxy)-3,4-difluorobenzamide
Synonyms	PD184161; PD 184161; PD184161
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	Inducing apoptosis and inhibiting cell proliferation, PD184161 (1–20 μM) exhibits concentration- and time-dependent effects [1]. A one-hour dose of 0.1 and 1.0 μM PD184161,2 inhibits phosphorylation of ERK1,2 [1]. PD184161 (5 μM; 30 min) protects against the toxic effects of bicuculline [3].
ln Vivo	After oral administration, PD184161 decreases P-ERK levels in tumor xenografts in 3–12 hours [1]. PD184161, administered orally twice daily for 38 days at a dose of 300 mg/kg, dramatically slowed the growth and implantation of tumors [1]. A single injection of PD184161, at a dose of 30 mg/kg, induces depressive-like symptoms [2]. After a stroke, PD184161, administered intravenously at a dose of 500 μg/kg, stops the progression of neurological impairments and brain damage [3].
Cell Assay	Cell Proliferation Assay[1] Cell Types: HCC cell lines (HepG2, Hep3B, PLC and SKHep) Tested Concentrations: 1-20 μM Incubation Duration: 24, 48 or 72 hrs (hours) Experimental Results: Cell proliferation was inhibited. Apoptosis analysis[1] Cell Types: HCC cell lines (HepG2, Hep3B, PLC and SKHep) Tested Concentrations: 1-20 μM Incubation Duration: 48 hrs (hours) Experimental Results: Induction of apoptosis. Western Blot Analysis[1] Cell Types: HCC cell lines (HepG2, Hep3B, PLC and SKHep) Tested Concentrations: 0.1 and 1.0 μM Incubation Duration: 1 hour Experimental Results: ERK1,2 phosphorylation is inhibited. Cell viability assay[3] Cell Types: Primary Mouse Neurons Tested Concentrations: 5 μM Incubation Duration: 30 min Experimental Results: Protection against toxic effects of bicuculline.
Animal Protocol	Animal/Disease Models: Hep3B tumor xenograft BALB/c athymic nude mice [1] Doses: 300 mg/kg Route of Administration: Orogastric gavage, twice a day for 38 days Experimental Results: diminished early tumor growth. Animal/Disease Models: Male, 6weeks old C57Bl/6 mice [2] Doses: 500 μg/kg Route of Administration: intravenous (iv) (iv)injection 30 minutes before MCAO or PTZ administration Experimental Results: Prevent the progression of neurological deficits and brain damage after stroke. Animal/Disease Models: C57Bl/6 mice [3] Doses: 30 mg/kg Route of Administration: intraperitoneal (ip) injection, single injection Experimental Results:depressive-like behavior.
References	[1]. 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]. A role for MAP kinase signaling in behavioral models of depression and antidepressant treatment. Biol Psychiatry. 2007 Mar 1;61(5):661-70. [3]. ERK inhibition with PD184161 mitigates brain damage in a mouse model of stroke. J Neural Transm (Vienna). 2014 May;121(5):543-7.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~179.35 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 2.5 mg/mL (4.48 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.48 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.7936 mL	8.9678 mL	17.9356 mL
	5 mM	0.3587 mL	1.7936 mL	3.5871 mL
	10 mM	0.1794 mL	0.8968 mL	1.7936 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.