JCN037 (JGK037) is a potent, covalent, BBB (blood-brain barrier) permeable (penetrable) EGFR inhibitor (antagonist) with IC50s of 2.49 nM, 3.95 nM and 4.48 nM for EGFR, p-wtEGFR and pEGFRvIII respectively.

Physicochemical Properties

Molecular Formula	C16H11BRFN3O2
Molecular Weight	376.179846048355
Exact Mass	375.001
CAS #	2305154-31-6
PubChem CID	138513760
Appearance	Off-white to light yellow solid powder
LogP	3.9
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	2
Heavy Atom Count	23
Complexity	419
Defined Atom Stereocenter Count	0
SMILES	BrC1=CC=CC(=C1F)NC1C2=CC3=C(C=C2N=CN=1)OCCO3
InChi Key	MTLUFWWVOINWEL-UHFFFAOYSA-N
InChi Code	InChI=1S/C16H11BrFN3O2/c17-10-2-1-3-11(15(10)18)21-16-9-6-13-14(23-5-4-22-13)7-12(9)19-8-20-16/h1-3,6-8H,4-5H2,(H,19,20,21)
Chemical Name	N-(3-bromo-2-fluorophenyl)-7,8-dihydro-[1,4]dioxino[2,3-g]quinazolin-4-amine
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	2.49 nM (EGFR), 3.95 nM (p-wtEGFR), 4.48 nM (pEGFRvⅢ)[1].
ln Vitro	In HK301 cells and GBM39 cells, JCN037 displays GI50 values of 329 nM and 1116 nM, respectively[1].
ln Vivo	Due to a fast hydroxylation of the fused 1,4-dioxane ring, compound 5, JCN037, shows limited oral bioavailability, indicating first pass metabolism[1]. Treatment with JCN037 (compound 5, 300 mg/kg, BID) significantly improves survival; median survival improved from 37.5 days to 55 days with 5 treatment, a 47% increase[1].
Cell Assay	Western Blot Analysis[1]. Cell Types: GBM39 and GS025 cells. Tested Concentrations: 0-3333 nM Incubation Duration: Experimental Results: Downregulated pEGFRvⅢ , p Akt, p-ERK, and p-S6 protein levels, dramatically.
References	[1]. Development of a Potent Brain-Penetrant EGFR Tyrosine Kinase Inhibitor against Malignant Brain Tumors. ACS Med. Chem. Lett. 2020. May 1.

Solubility Data

Solubility (In Vitro)

DMSO: 250 mg/mL (664.58 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 6.25 mg/mL (16.61 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 62.5 mg/mL clear DMSO stock solution to 900 μL 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	2.6583 mL	13.2915 mL	26.5830 mL
	5 mM	0.5317 mL	2.6583 mL	5.3166 mL
	10 mM	0.2658 mL	1.3292 mL	2.6583 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.