NT-113

NT-113 is an irreversible pan-ERBB inhibitor, with IC50s of 0.4, 4.35, 4.18 and 2.08 nM for EGFR, EGFRT790M, ERBB2/HER2 and ERBB4/HER4, respectively, exhibiting anti-glioma activities.

Research Areas >> Cancer

EGFR:0.4 nM (IC50)

ErbB2:4.18 nM (IC50)

ErbB4:2.08 nM (IC50)

EGFRT790M:4.35 nM (IC50)

NT113 shows inhibitory activity against U87vIII cells, with IC50 of 0.19 μM[1].

NT113 (20 mg/kg/day) shows inhibitory activity against intracranial EGFRvIII-amplified GBM39 xenograft tumors. NT113 (10 mg/kg/day) causes growth delay in the U87vIII intracranial xenografts. Mice receiving NT113 treatment survive significantly longer than mice receiving lapatinib[1].

Cells are seeded in 96 well plates: 2000 cells/well in 200 μL, in hextuplicate. One day after seeding, 1 μL of DMSO, with or without NT113, is added to cells to achieve NT113 concentrations between 0.01 and 20.0 μM. Seventy-two hours later, WST-1 reagent is added, and sample 450 nm absorbance determined using a microplate reader, with background reading at 800 nm subtracted.

Mice with intracranial GBM12 tumors are administered NT113, at 10 mg/kg/day for 3 days, with blood and intracranial tissue samples obtained 2 hours following the third administration. Plasma is separated from whole blood, and frozen at −80°C. After brain resection, tumor tissue is immediately dissected from tumor-bearing hemisphere, then snap frozen and stored at −80°C, as is contralateral hemisphere without tumor. NT113 is extracted from homogenized tissues using a Bullet Blender. Homogenates are extracted with organic solvent and further processed prior to transfer to an autosampler for high performance liquid chromatography (HPLC) analysis, and determination of NT113 content.

[1]. Yoshida Y, et al. NT113, a pan-ERBB inhibitor with high brain penetrance, inhibits the growth of glioblastoma xenografts with EGFR amplification. Mol Cancer Ther. 2014 Dec;13(12):2919-29

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