EGF816 mesylate

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

EGF816 (Nazartinib) 是一种有效的、不可逆的、突变选择性 EGFR 抑制剂，Ki 和 Kinact 分别为 31 nM 和 0.222 min-1。

EGF816 (Nazartinib) is a potent, irreversible, mutant-selective EGFR inhibitor with Ki and Kinact of 31 nM and 0.222 min-1, respectively; shows potent inhibition of pEGFR levels in H3255, HCC827, and H1975 with EC50 of 5, 1, and 3 nM, which harbor the L858R, Ex19del, and L858R/T790M mutations, respectively, inhibitscell proliferation with EC50 of 9, 11, and 25 nM, but not the WT EGFR-containing patient-derived cell lines; potently inhibits the most common EGFR mutations L858R, Ex19del, and T790M in vitro; causes tumor regressions in vivo in several patient-derived xenograft models, also demonstrates antitumor activity in exon 20 insertion mutant model.Lung Cancer Phase 3 Clinical.

Nazartinib (EGF816) has inhibitory effect on the mutant cell lines with IC50s of 4, 6, 2 nM in H1975, H3255, and HCC827, respectively, and demonstrates improved ADME and PK properties. Nazartinib (EGF816) shows potent inhibition of pEGFR levels in H3255, HCC827, and H1975 cell lines with EC50 values of 5, 1, and 3 nM, respectively. Nazartinib inhibits cell proliferation, with EC50 values of 9, 11, and 25 nM in H3255, HCC827, and H1975, respectively. Nazartinib has an OC50 (compound concentration at 50% occupancy) value of 2 and 5 nM on HCC827 and H1975, respectively.

In H1975 mouse xenograft model, Nazartinib (EGF816; 50 and 20 mg/kg or 25 mg/kg, p.o.) demonstrates dose-dependent efficacy with near complete tumor cells regression at the highest dose tested (50 mg/kg). In H1975 mouse model, Nazartinib (EGF816; 10 mg/kg, p.o.) induces tumor growth inhibition with a T/C (tumor/control volume) of 29%, and when doses are 30 and 100 mg/kg, tumor regressions are achieved (T/C, ?61% and ?80%, respectively). In the H3255 xenograft model, Nazartinib (30 mg/kg, p.o.) shows significant antitumor activity. Antiproliferative activity of Nazartinib on 89 lung cancer cell lines indicates that Nazartinib selectively inhibits cell lines containing EGFR with catalytic domain mutations.

EGF-816 mesylate | Nazartinib mesylate

Angiogenesis

EGFR

EGFR

Cancer

Lung Cancer

1508250-72-3

591.122

C27H35ClN6O5S

>98% (HPLC)

10 mM in DMSO

CC1=NC=CC(=C1)C(=O)NC2=NC3=C(N2C4CCCCN(C4)C(=O)C=CCN(C)C)C(=CC=C3)Cl.CS(=O)(=O)O

4-Pyridinecarboxamide, N-[7-chloro-1-[(3R)-1-[(2E)-4-(dimethylamino)-1-oxo-2-buten-1-yl]hexahydro-1H-azepin-3-yl]-1H-benzimidazol-2-yl]-2-methyl-, methanesulfonate (1:1)

(-20℃)

With Ice Pack

≥ 2 years