JNJ-38158471 is a well-tolerated, orally bioactive, selective VEGFR-2 inhibitor (antagonist) with IC50 of 40 nM. JNJ-38158471 also inhibits Ret and Kit with IC50s of 180 and 500 nM, respectively.

Physicochemical Properties

Molecular Formula	C15H17CLN6O3
Molecular Weight	364.78688120842
Exact Mass	364.105
CAS #	951151-97-6
PubChem CID	16742063
Appearance	Gray to brown solid powder
Density	1.4±0.1 g/cm3
Index of Refraction	1.637
LogP	4.05
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	6
Heavy Atom Count	25
Complexity	455
Defined Atom Stereocenter Count	0
SMILES	CCNC(=O)NC1=C(C=C(C=C1)OC2=NC=NC(=C2/C=N/OC)N)Cl
InChi Key	BJHCYTJNPVGSBZ-QPSGOUHRSA-N
InChi Code	InChI=1S/C15H17ClN6O3/c1-3-18-15(23)22-12-5-4-9(6-11(12)16)25-14-10(7-21-24-2)13(17)19-8-20-14/h4-8H,3H2,1-2H3,(H2,17,19,20)(H2,18,22,23)/b21-7+
Chemical Name	1-[4-[6-amino-5-[(E)-methoxyiminomethyl]pyrimidin-4-yl]oxy-2-chlorophenyl]-3-ethylurea
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 HUVECs, VEGF-stimulated VEGFR-2 autophosphorylation is inhibited by JNJ-38158471 (1-500 nM; 1 hour) [1]. JNJ-38158471 (50-1000 nM; 12-16 hours) strongly suppresses HUVEC migration that is dependent on VEGF. HUVEC were treated with JNJ-38158471; no cytotoxicity was seen [1].
ln Vivo	JNJ-38158471 (10 or 100 mg/kg; oral; once daily) prevents VEGF-induced ocular neovascularization [1]. JNJ-38158471 (10-200 mg/kg; oral) suppresses the growth of human tumor xenografts in a dose-dependent manner in A431 and HCT116 models. JNJ-38158471 therapy was well tolerated, and after 24 days of continuous administration, the body weight was comparable to that of control animals [1]. JNJ-38158471 (100 mg/kg; oral; once daily) therapy revealed statistically significant action compared to vehicle-treated mice. At the end of the research, body weights were comparable between the JNJ-38158471 and vehicle-treated groups [1].
Cell Assay	Western blot analysis [1] Cell Types: Human umbilical vein endothelial cells (HUVEC) Tested Concentrations: 1, 10, 100, 500 nM Incubation Duration: 1 hour Experimental Results: The concentrations used were 500, 100, 10 and 1nM respectively.
Animal Protocol	Animal/Disease Models: Female C57BL/6J mice implanted with rhVEGF165[1] Doses: 10 or 100 mg/kg Route of Administration: Daily oral administration for 6 days Experimental Results: Obvious dose dependence on VEGF-dependent vascularization Inhibition (100 mg/kg, resulted in 83% inhibition; 10 mg/kg, resulted in 15% inhibition). Animal/Disease Models: female athymic nude mice; 5-6 weeks; subcutaneously (sc) (sc) implanted with human colorectal cancer cells (HCT116) or human epidermoid cancer cells (A431) [1] Doses: 10, 50, 100, 200 mg/kg given Medication method: Oral administration for 35 days. Experimental Results: Optimum efficacy is achieved when the dosage is from 100 to 200 mg/kg daily. Animal/Disease Models: Female athymic nude mice; 5-6 weeks; subcutaneousimplantation of human skin melanoma cells (A375) [1] Doses: 100 mg/kg Route of Administration: Oral one time/day for 28 days Experimental Results: Daily A dose of 100 mg/kg can inhibit 90% of tumor growth. Animal/Disease Models: Female C57BL/6J-Apc Min mice; 5 weeks old [1] Doses: 100 mg/kg Route of Administration: Orally once d
References	[1]. A Highly Selective, Orally Bioavailable, Vascular Endothelial Growth Factor receptor-2 Tyrosine Kinase Inhibitor Has Potent Activity in Vitro and in Vivo. Angiogenesis. 2009; 12(3): 287-96.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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	2.7413 mL	13.7065 mL	27.4130 mL
	5 mM	0.5483 mL	2.7413 mL	5.4826 mL
	10 mM	0.2741 mL	1.3707 mL	2.7413 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.