PF-02413873 (PF-2413873) is a potent, selective, fully competitive and orally bioactive non-steroidal progesterone receptor (PR) antagonist (inhibitor) with Ki of 2.6 nM. PF-02413873 blocks progesterone binding and PR nuclear translocation and inhibits endometrial growth in vivo.

Physicochemical Properties

Molecular Formula	C18H21N3O3S
Molecular Weight	359.44
Exact Mass	359.13
CAS #	936345-35-6
PubChem CID	16662425
Appearance	White to light yellow solid powder
LogP	4.432
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	5
Heavy Atom Count	25
Complexity	622
Defined Atom Stereocenter Count	0
InChi Key	QSFGZNVRVZHUGV-UHFFFAOYSA-N
InChi Code	InChI=1S/C18H21N3O3S/c1-11-7-15(8-12(2)16(11)9-19)24-18-13(3)21(10-25(4,22)23)20-17(18)14-5-6-14/h7-8,14H,5-6,10H2,1-4H3
Chemical Name	4-[3-cyclopropyl-5-methyl-1-(methylsulfonylmethyl)pyrazol-4-yl]oxy-2,6-dimethylbenzonitrile
Synonyms	PF02413873; PF-02413873; PF-02413873
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
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	In a T47D native functional test, PF-02413873 demonstrated strong PR antagonist action with a derived Ki of 9.7 nM [1]. Nuclear translocation is exclusively induced by PF-02413873 (1 nM–10 μM) at high concentrations (>3 μM) [1].
ln Vivo	In monkeys that consume crabs, PF-02413873 (2.5 and 10 mg/kg; administered orally twice daily for 10 days) reduces endometrial thickness in a statistically significant way [1]. The following results were shown by PF-02413873 (3 mg/kg; single oral dose): t1/2 (4.2 h), Cmax (162 ng/mL), and CL/F (41 mL/min/kg) [1].
Animal Protocol	Animal/Disease Models: Cynomolgus monkey (3.7-5.7 kg; 5-6 years old) [1] Doses: 3 mg/kg (pharmacokinetic/PK/PK analysis) Route of Administration: Single oral dose Experimental Results: t1/2=4.2 h, Cmax =162 ng/mL, CL/F=41 ml/min/kg.
References	[1]. The translational efficacy of a nonsteroidal progesterone receptor antagonist, 4-[3-cyclopropyl-1-(mesylmethyl)-5-methyl-1H-pyrazol-4-yl]oxy,-2,6-dimethylbenzonitrile (PF-02413873), on endometrial growth in macaque and human. J Pharmacol. [2]. Preclinical and clinical pharmacokinetics of PF-02413873, a nonsteroidal progesterone receptor antagonist. Drug Metab Dispos. 2011 Aug;39(8):1396-405.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~278.21 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.25 mg/mL (3.48 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 12.5 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: ≥ 1.25 mg/mL (3.48 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 12.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 1.25 mg/mL (3.48 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 12.5 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	2.7821 mL	13.9105 mL	27.8211 mL
	5 mM	0.5564 mL	2.7821 mL	5.5642 mL
	10 mM	0.2782 mL	1.3911 mL	2.7821 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.