138736-73-9|HAMNO|CsnPharm

CAS No.: 138736-73-9

HAMNO Catalog No. CSN26246

Synonyms: NSC111847;CID 6335338;MLS000737724

HAMNO is a potent and selective inhibitor of replication protein A (RPA) interactions with proteins involved in the replication stress response. It has shown to significantly inhibits colony formation when combined with etoposide.

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技术信息

生物活性

描述Replication protein A (RPA), a major eukaryotic ssDNA-binding protein, is essential for all metabolic processes that involve ssDNA, including DNA replication, repair, and damage signaling^[1]. During DNA replication stress, RPA binds the ssDNA exposed downstream of stalled primer/template (P/T) junctions, releasing Rad6/Rad18. RPA restricted the resident PCNAs to the upstream duplex regions by physically blocking diffusion of PCNA along ssDNA, and this activity was required for efficient monoubiquitination of PCNA on DNA^[2]. HAMNO is a potent and selective inhibitor of replication protein A (RPA) interactions with proteins involved in the replication stress response. HAMNO was first identified as a RPA DBD-F inhibitor. It affects RPA and ATR phosphorylation directly by inhibiting DBD-F interactions with replication stress response protein involved in activating ATR. Ser22 of RPA showed highly phosphorylated after 2 h of treatment with 20μM of etoposide, which is reduced with the addition of 2 μM HAMNO. 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^[3].The experiment of Fanconi anemia (FA) repair pathway, which is induced by RPA, showed that HAMNO significantly induced FANCD2 monoubiquitination and foci formation and also caused increased level of γ-H2AX and S-phase accumulation in FA-deficient cells^[4].
参考文献

[1] Olga M Mazina,et al. Replication protein A binds RNA and promotes R-loop formation. J Biol Chem. 2020. 295(41), 14203-14213.
[2] Mark Hedglin,et al. Replication protein A dynamically regulates monoubiquitination of proliferating cell nuclear antigen. J Biol Chem. 2019. 294(13), 5157-5168.
[3] Glanzer JG, et al. RPA inhibition increases replication stress and suppresses tumor growth. Cancer Res. 2014. 74(18), 5165-72.
[4] Jang, S., Kim, J. M. The RPA inhibitor HAMNO sensitizes Fanconi anemia pathway-deficient cells. Cell cycle. 2022. 21(14), 1468-1478.

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 3.7981 mL
- 18.9904 mL
- 37.9808 mL
- 5 mM
- 0.7596 mL
- 3.7981 mL
- 7.5962 mL
- 10 mM
- 0.3798 mL
- 1.8990 mL
- 3.7981 mL

技术信息

CAS号	138736-73-9	储存条件	粉末 Keep in dark place,Sealed in dry,2-8°C 液体 -20°C:3-6 月 -80°C:12月
分子式	C17H13NO2	运输	蓝冰
分子量	263.29	别名	NSC111847;CID 6335338;MLS000737724

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