DBPR112 is an orally bioactive fluoropyrimidine-based EGFR inhibitor (antagonist) with IC50s of 15 nM and 48 nM for EGFRWT and EGFRL858R/T790M, respectively. DBPR112 can occupy the ATP binding site. DBPR112 has significant anti-tumor efficacy.

Physicochemical Properties

Molecular Formula	C32H31N5O3
Molecular Weight	533.6202
Exact Mass	533.242
CAS #	1226549-49-0
PubChem CID	46212971
Appearance	Off-white to light yellow solid powder
LogP	4.9
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	10
Heavy Atom Count	40
Complexity	812
Defined Atom Stereocenter Count	1
SMILES	O1C2C(=C(N=C([H])N=2)N([H])[C@]([H])(C([H])([H])O[H])C2C([H])=C([H])C([H])=C([H])C=2[H])C(C2C([H])=C([H])C([H])=C(C=2[H])N([H])C(/C(/[H])=C(\[H])/C([H])([H])N(C([H])([H])[H])C([H])([H])[H])=O)=C1C1C([H])=C([H])C([H])=C([H])C=1[H]
InChi Key	NQAMTZUVRFRJCZ-VMMYIZNOSA-N
InChi Code	InChI=1S/C32H31N5O3/c1-37(2)18-10-17-27(39)35-25-16-9-15-24(19-25)28-29-31(36-26(20-38)22-11-5-3-6-12-22)33-21-34-32(29)40-30(28)23-13-7-4-8-14-23/h3-17,19,21,26,38H,18,20H2,1-2H3,(H,35,39)(H,33,34,36)/b17-10+/t26-/m1/s1
Chemical Name	(E)-4-(dimethylamino)-N-[3-[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-6-phenylfuro[2,3-d]pyrimidin-5-yl]phenyl]but-2-enamide
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	EGFRL858R/T790M 48 nM (IC50) EGFRWT 15 nM (IC50)
ln Vitro	In a dose-dependent manner, DBPR112 (compound 78; 0.32-1000 nM; 16 hours) reduces phosphorylated EGFR[1]. HCC827 (CC50=25 nM), H1975 (CC50=620 nM), and A431 Cell (CC50=1.02 μM) cell lines are all inhibited by DBPR112[1]. With its occupation of the ATP-binding site and its interactions—covalent, hydrogen, and hydrophobic—with neighboring residues, DBPR112 exhibits a strong inhibitory effect on WT EGFR[1].
ln Vivo	In the HCC827 tumor model, DBPR112 (orally administered at 20–50 mg/kg, five days per week for two weeks in a row) dramatically slows tumor growth. In the H1975 tumor model, DBPR112 (orally; 50 mg/kg; once daily for 15 days) significantly inhibits tumor development (mean tumor growth suppression of 34%)[1]. The T1/2, CL, and Vss of DBPR112 (IV; 5 mg/kg) in rats are 2.3 hours, 55.6 mL/min·kg, and 8.6 L/kg, respectively[1].
Cell Assay	Western Blot Analysis[1] Cell Types: H1975 cells Tested Concentrations: 0.32, 1.6, 8.0, 40, 200, 1000 nM Incubation Duration: 16 hrs (hours) Experimental Results: Induced reduction of phosphorylated EGFR in a dose-dependent manner in H1975 cells.
Animal Protocol	Animal/Disease Models: HCC827 tumor model (6- to 8weeks old athymic NU-Fox1nu nude mice)[1] Doses: 20, 50 mg/kg Route of Administration: po (oral gavage) 5 days/week for 2 consecutive weeks (days 1-5 and 8-12) Experimental Results: Dramatically decreased tumor growth. Animal/Disease Models: Rats[1] Doses: 5 mg/kg for IV and 20 mg/kg for PO (pharmacokinetic/PK Analysis) Route of Administration: IV or PO Experimental Results: Had a T1/2 of 2.3 hrs (hours), a CL of 55.6 mL/min·kg, and a Vss of 8.6 L/kg by IV. Had a T1/2 of 3.4 hrs (hours), a Cmax of 508 ng/mL and an AUC of 2978 ng/mL·h by PO.
References	[1]. Discovery of a Furanopyrimidine-Based Epidermal Growth Factor Receptor Inhibitor (DBPR112) as a Clinical Candidate for the Treatment of Non-Small Cell Lung Cancer. J Med Chem. 2019 Nov 27;62(22):10108-10123.

Solubility Data

Solubility (In Vitro)

DMSO: 250 mg/mL (468.50 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (3.90 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.08 mg/mL (3.90 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 2.08 mg/mL (3.90 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 20.8 mg/mL clear DMSO stock solution to 900 μL of 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	1.8740 mL	9.3700 mL	18.7399 mL
	5 mM	0.3748 mL	1.8740 mL	3.7480 mL
	10 mM	0.1874 mL	0.9370 mL	1.8740 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.