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CAS号:138736-73-9
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英文名称:HAMNO
分子式
C17H13NO2
分子量
263
EINECS号
604-604-1
MDL
Smiles
InChIKey
乙二醇化学百科
基本信息
物化性质
安全信息
生产及用途
HAMNO (NSC-111847) 是一种有效的、选择性的、具有抗肿瘤活性的 replication protein A (RPA) 的抑制剂。HAMNO 可抑制 ATR 的自磷酸化及ATR诱导的RPA32 Ser33磷酸化。
HAMNO is a novel protein interaction inhibitor of replication protein A (RPA). RPA is involved in the ATR/Chk1 pathway. HAMNO alone inhibits colony formation in both HNSCC cell lines in the low micromolar range. HAMNO combined with etoposide significantly inhibits colony formation to a greater degree than HAMNO alone. After UMSCC38 cells are exposed to HAMNO, increased pan-nuclear γ-H2AX staining occurs in a dose dependent manner. Cancer derived UMSCC38 cells, as well as another cancer cell line, UMSCC11B, have prominent γ-H2AX staining, particularly after incubation with 20 μM HAMNO. Both UMSCC38 and OKF4 cells present increased γ-H2AX staining after addition of HAMNO, with the greatest increase in signal occurring in S-phase.
In mice, HAMNO slows the progression of UMSCC11B tumors. Ser33 of RPA32, an ATR substrate, is highly phosphorylated after two hours of treatment with 20 μM of etoposide, which is reduced with the addition of 2 μM HAMNO, and is nearly absent at higher concentrations, demonstrating an in vivo effect of HAMNO as an inhibitor of RPA32 phosphorylation by ATR.
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