DBPR112

• CAT Number: I017821
• CAS Number: 1226549-49-0
• Molecular Formula: C32H31N5O3
• Molecular Weight: 533.62
• Purity: ≥95%
• Synonyms: (E)-4-(dimethylamino)-N-[3-[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-6-phenylfuro[2,3-d]pyrimidin-5-yl]phenyl]but-2-enamide
• InChI: 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
• InChIKey: NQAMTZUVRFRJCZ-VMMYIZNOSA-N
• SMILES: CN(C)CC=CC(=O)NC1=CC=CC(=C1)C2=C(OC3=NC=NC(=C23)NC(CO)C4=CC=CC=C4)C5=CC=CC=C5

DBPR112 is an orally active furanopyrimidine-based EGFR inhibitor with IC50s of 15 nM and 48 nM for EGFRWT and EGFRL858R/T790M, respectively. DBPR112 can occupy the ATP-binding site. DBPR112 has significant antitumor efficacy[1].
DBPR112 (compound 78; 0.32-1000 nM; 16 hours) induces reduction of phosphorylated EGFR in a dose-dependent manner[1].
DBPR112 shows the inhibitory activity against HCC827 (CC50=25 nM), H1975 (CC50=620 nM) and A431 Cell (CC50=1.02 μM) cell lines[1].
DBPR112 occupies the ATP-binding site and interacts with surrounding residues by covalent bonding, hydrogen bonds, and hydrophobic interactions, which give it a potent inhibitory activity against WT EGFR[1].
DBPR112 (orally; 20-50 mg/kg; 5 days/week for 2 consecutive weeks) significantly reduces tumor growth in HCC827 tumor model. DBPR112 (orally; 50 mg/kg; once a day for 15 days) has a significant antitumor effect (mean tumor growth inhibition of 34%) in H1975 tumor model[1].
DBPR112 (IV; 5 mg/kg) has a T1/2 of 2.3 hours, a CL of 55.6 mL/min•kg, and a Vss of 8.6 L/kg for rats[1].

Reference

[1]. Lin SY, et al. 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.
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