sb-435495 ( sb435495), inhibitor of Lp-PLA2 (IC50 = 0.06 nM) with anti-Atherosclerosis activity. It suppresses BRB breakdown in streptozotocin-diabetic Brown Norway rats,

Physicochemical Properties

Molecular Formula	C38H40N6O2F4S
Molecular Weight	720.8218
Exact Mass	720.286
CAS #	304694-39-1
Related CAS #	SB-435495 hydrochloride;304694-41-5;SB-435495 ditartrate;304694-43-7
PubChem CID	10417440
Appearance	White to off-white solid powder
Density	1.3±0.1 g/cm3
Boiling Point	793.9±70.0 °C at 760 mmHg
Flash Point	433.9±35.7 °C
Vapour Pressure	0.0±2.8 mmHg at 25°C
Index of Refraction	1.595
LogP	7.48
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	15
Heavy Atom Count	51
Complexity	1190
Defined Atom Stereocenter Count	0
InChi Key	VGIQUSQBXZXBGW-UHFFFAOYSA-N
InChi Code	InChI=1S/C38H40F4N6O2S/c1-4-46(5-2)18-19-47(23-27-6-10-30(11-7-27)31-12-14-33(15-13-31)38(40,41)42)35(49)25-48-24-32(20-29-21-43-45(3)22-29)36(50)44-37(48)51-26-28-8-16-34(39)17-9-28/h6-17,21-22,24H,4-5,18-20,23,25-26H2,1-3H3
Chemical Name	N-[2-(diethylamino)ethyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(1-methylpyrazol-4-yl)methyl]-4-oxopyrimidin-1-yl]-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]acetamide
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: Please store this product in a sealed and protected environment, avoid exposure to moisture.
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	At a 10 μM IC50 and a 0.017 cm/h membrane permeability, SB-435495 inhibits CYP450 3A4[1]. While oxLDL has a greater effect on HUVEC SB-435495 (5 μM; 24-72 h), it greatly reduces the expression of Lp-PLA2 protein. dramatically lowers ET-1 expression and dramatically boosts cell survival [2]. The phospho-AMPKα (T172) and AMPKα expression levels [2].
ln Vivo	SB-435495 (10 mg/kg; po; once) inhibits Lp-PLA2 coagulation in WHHL rabbits [1]. SB-435495 (10 mg/kg; ip; daily for 28 days) efficiently suppresses disruption of blood connectivity (BRB) in streptozotocin diabetic Norwegian solution [3].
Cell Assay	Western Blot analysis [2] Cell Types: oxLDL-exposed human umbilical vein endothelial cells Tested Concentrations: 5μM Incubation Duration: 24 hrs (hours) Experimental Results: The expression of Lp-PLA2 protein was Dramatically inhibited. Increases the expression levels of AMPKα and phosphorylated AMPKα (T172). Cell viability assay[2] Cell Types: oxLDL Exposed Human Umbilical Vein Endothelial Cells Tested Concentrations: 5 μM Incubation Duration: 24, 48 and 72 hrs (hours) Experimental Results: Significant increase in cell viability.
References	[1]. The discovery of SB-435495. A potent, orally active inhibitor of lipoprotein-associated phospholipase A(2) for evaluation in man. Bioorg Med Chem Lett. 2002 Sep 16;12(18):2603-6. [2]. AMP-activated protein kinase mediates the effects of lipoprotein-associated phospholipase A2 on endothelial dysfunction in atherosclerosis. Exp Ther Med. 2017 Apr;13(4):1622-1629. [3]. Lipoprotein-associated phospholipase A2 (Lp-PLA2) as a therapeutic target to prevent retinal vasopermeability during diabetes. Proc Natl Acad Sci U S A. 2016 Jun 28;113(26):7213-8.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~138.73 mM)

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	1.3873 mL	6.9365 mL	13.8731 mL
	5 mM	0.2775 mL	1.3873 mL	2.7746 mL
	10 mM	0.1387 mL	0.6937 mL	1.3873 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.