JNJ28871063 HCl is an orally bioactive, selective and ATP-competitive pan-ErbB kinase inhibitor (antagonist) with IC50s of 22 nM, 38 nM and 21 nM for ErbB1, ErbB2 and ErbB4 respectively. JNJ28871063 HCl inhibits the phosphorylation of functionally important tyrosine residues in EGFR and ErbB2. JNJ28871063 HCl can penetrate the BBB (blood-brain barrier) and has anti-tumor activity in human tumor xenograft models overexpressing EGFR and ErbB2.

Physicochemical Properties

Molecular Formula	C24H28CL2N6O3
Molecular Weight	519.42
Exact Mass	518.16
CAS #	944342-90-9
PubChem CID	17747413
Appearance	Typically exists as solid at room temperature
LogP	5.111
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	10
Heavy Atom Count	35
Complexity	605
Defined Atom Stereocenter Count	0
SMILES	N(C1C=CC(OCC2C=CC=CC=2)=C(Cl)C=1)C1=NC=NC(N)=C1/C=N/OCCN1CCOCC1.Cl
InChi Key	ZXKZRKQMKNRZNN-GZPZNDDGSA-N
InChi Code	InChI=1S/C24H27ClN6O3.ClH/c25-21-14-19(6-7-22(21)33-16-18-4-2-1-3-5-18)30-24-20(23(26)27-17-28-24)15-29-34-13-10-31-8-11-32-12-9-31;/h1-7,14-15,17H,8-13,16H2,(H3,26,27,28,30);1H/b29-15+;
Chemical Name	4-N-(3-chloro-4-phenylmethoxyphenyl)-5-[(E)-2-morpholin-4-ylethoxyiminomethyl]pyrimidine-4,6-diamine;hydrochloride
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	ErbB1 22 nM (IC50) ErbB2 38 nM (IC50) ErbB4 21 nM (IC50)
ln Vitro	Human cancer cell lines (N87; BT474; SKBR3; A431; HN5) overexpressing the ErbB2 receptor show strong growth inhibition in vitro when treated with JNJ-28871063, with IC50 values ranging from 60 to 168 nM. When it came to preventing the growth of primary fibroblast cells (HeLa, A375, HCT116, HT29, and MRC5) that did not overexpress ErbB, 28871063, had the least amount of effect (IC50>10 μM)[1]. ErbB2 phosphorylation in SKBR3 cells is decreased at the basal level by JNJ-28871063 hydrochloride (3 μM; 16 hours) [1]. The hydrochloride JNJ28871063 belongs to the aminopyrimidine oxime structural class[1].
ln Vivo	For 30 days, JNJ28871063 hydrochloride (100 mg/kg/day; oral; TGI=71%) significantly inhibits tumor growth[1]. In an A431 human tumor xenograft model, JNJ28871063 hydrochloride significantly inhibits tumor development at 100 mg/kg (TGI=66.8%][1].
Cell Assay	Western Blot Analysis[1] Cell Types: BT474 cells Tested Concentrations: 3 μM Incubation Duration: 16 hrs (hours) Experimental Results: diminished the basal level of ErbB2 phosphorylation.
Animal Protocol	Animal/Disease Models: Nude mice bearing N87 tumor xenografts[1] Doses: 100 mg/kg Route of Administration: Oral; daily for 30 days Experimental Results: demonstrated significant inhibition of tumor growth (TGI= 71%).
References	[1]. Cellular and in vivo activity of JNJ-28871063, a nonquinazoline pan-ErbB kinase inhibitor that crosses the blood-brain barrier and displays efficacy against intracranial tumors. Mol Pharmacol. 2008 Feb;73(2):338-48.

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	1.9252 mL	9.6261 mL	19.2522 mL
	5 mM	0.3850 mL	1.9252 mL	3.8504 mL
	10 mM	0.1925 mL	0.9626 mL	1.9252 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.