PF429242 (PF-429242) is a novel, potent, reversible and competitive S1P [sterol regulatory element-binding protein (SREBP) site 1 protease] inhibitor with an IC50 of 170 nM. PF 429242 demonstrated only mild inhibition of urokinase (IC50 = 50 μM) and factor Xa (IC50 = 100 μM), and no significant inhibition of trypsin, elastase, proteinase K, plasmin, kallikren, factor XIa, thrombin, or furin at concentrations up to 100 μM. PF-429242 exhibits selectivity towards site 1 protease in contrast to a group of serine proteases. PF-429242 has an IC50 of 0.53 μM and inhibits the rate of cholesterol synthesis in CHO cells.

Physicochemical Properties

Molecular Formula	C25H35N3O2
Molecular Weight	409.5643
Exact Mass	409.272
Elemental Analysis	C, 73.31; H, 8.61; N, 10.26; O, 7.81
CAS #	947303-87-9
Related CAS #	PF429242 dihydrochloride; 2248666-66-0
PubChem CID	23661637
Appearance	Solid powder
Density	1.1±0.1 g/cm3
Boiling Point	562.2±50.0 °C at 760 mmHg
Flash Point	293.8±30.1 °C
Vapour Pressure	0.0±1.5 mmHg at 25°C
Index of Refraction	1.586
LogP	2.88
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	10
Heavy Atom Count	30
Complexity	503
Defined Atom Stereocenter Count	1
SMILES	N([C@H]1CNCC1)(CCC1C=CC=CC=1OC)C(C1C=CC(CN(CC)CC)=CC=1)=O
InChi Key	XKPJTOHUPQWSOJ-HSZRJFAPSA-N
InChi Code	InChI=1S/C25H35N3O2/c1-4-27(5-2)19-20-10-12-22(13-11-20)25(29)28(23-14-16-26-18-23)17-15-21-8-6-7-9-24(21)30-3/h6-13,23,26H,4-5,14-19H2,1-3H3/t23-/m1/s1
Chemical Name	4-(diethylaminomethyl)-N-[2-(2-methoxyphenyl)ethyl]-N-[(3R)-pyrrolidin-3-yl]benzamide
Synonyms	PF 429242; PF-429242; PF429242
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

Targets	S1P ( IC50 = 170 nM )
ln Vitro	PF-429242 suppresses the expression of important genes involved in the synthesis of fatty acids and cholesterol, stops the nuclear translocation of SREBP, and inhibits both pathways in cultured human liver (Hep-G2) cells without causing any cytotoxicity[1]. In various cells derived from primates, the addition of PF-429242 inhibits the viral propagation of all DENV serotypes[2].
ln Vivo	PF-429242's PK data in rats indicate that it had a low oral bioavailability of 5% and a rapid clearance of 75 ml/min/kg[1].
Cell Assay	HeLa cells are cultivated in medium enhanced with 2% FCS and 0.2 mM non-essential amino acids, containing 3 to 300 µM of PF-429242. The cultured cells are given a CellTiter-Glo mixture 72 hours after the medication is administered, and the intracellular ATP is measured for luminescence intensity using an ARVO MX/Light 1420 Multilabel/Luminescence counter.
References	[1]. Bioorg Med Chem Lett . 2007 Aug 15;17(16):4411-4. [2]. Viruses . 2016 Feb 10;8(2):46.

Solubility Data

Solubility (In Vitro)

DMSO: ~82 mg/mL (~200.2 mM) Water: ~82 mg/mL Ethanol: ~82 mg/mL

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.4416 mL	12.2082 mL	24.4164 mL
	5 mM	0.4883 mL	2.4416 mL	4.8833 mL
	10 mM	0.2442 mL	1.2208 mL	2.4416 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.