DBPR112

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

DBPR112 是一种口服有效的基于氟嘧啶的 EGFR 抑制剂，对 EGFRWT 和 EGFRL858R/T790M 的 IC50 分别为 15 nM 和 48 nM。DBPR112 可以占据 ATP 结合位点。DBPR112 具有显着的抗肿瘤功效。

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.

DBPR112 (compound 78; 0.32-1000 nM; 16 hours) induces reduction of phosphorylated EGFR in a dose-dependent manner. DBPR112 shows the inhibitory activity against HCC827 (CC50=25 nM), H1975 (CC50=620 nM) and A431 Cell (CC50=1.02 μM) cell lines. 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. Western Blot Analysis Cell Line: H1975 cells Concentration:0.32, 1.6, 8.0, 40, 200, 1000 nM Incubation Time:16 hours Result:Induced reduction of phosphorylated EGFR in a dose-dependent manner in H1975 cells.

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. 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. Animal Model:HCC827 tumor model (6- to 8-week-old athymic NU-Fox1nu nude mice) Dosage:20, 50 mg/kg Administration: Orally; 5 days/week for 2 consecutive weeks (days 1-5 and 8-12)Result:Significantly reduced tumor growth. Animal Model:Rats Dosage:5 mg/kg for IV and 20 mg/kg for PO (Pharmacokinetic Analysis) Administration:IV or PO Result:Had a T1/2 of 2.3 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 hours, a Cmax of 508 ng/mL and an AUC of 2978 ng/mL?h by PO.

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Angiogenesis

EGFR

EGFR

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1226549-49-0

533.62

C32H31N5O3

>98% (HPLC)

In Vitro:?DMSO 中的溶解度 : 250 mg/mL (468.50 mM; 超声助溶 )

CN(C)C\C=C\C(=O)Nc1cccc(c1)-c1c(oc2ncnc(N[C@H](CO)c3ccccc3)c12)-c1ccccc1

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(-20℃)

With Ice Pack

≥ 2 years