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Purity: ≥98%
HAMNO (formerly known as NSC-111847) is a novel, potent and selective protein interaction inhibitor of replication protein A (RPA). The replication stress response proteins and RPA are thought to interact. The N-terminal domain of RPA70 is specifically bound by HAMNO, effectively inhibiting the crucial RPA protein interactions that rely on this domain. HAMNO prevents ATR from phosphorylating itself as well as RPA32 Ser33. HAMNO treatment acts synergistically with etoposide to kill cancer cells in vitro and slow tumor growth in vivo, but it does not cause DNA replication stress on its own in normal cells or in cancer cells that are already under replication stress. As a result, HAMNO shows how RPA inhibitors are potential therapeutics for the treatment of cancer, offering disease selectivity in cancer cells by focusing on their various responses to replication stress.
| Targets |
RPA
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| ln Vitro |
HAMNO is a novel protein interaction inhibitor of replication protein A (RPA). The ATR/Chk1 pathway includes RPA. In both HNSCC cell lines, HAMNO inhibits colony formation at low micromolar concentrations. Colony formation is significantly inhibited by HAMNO and etoposide when compared to HAMNO alone. A dose-dependent increase in pan-nuclear -H2AX staining happens after UMSCC38 cells are exposed to HAMNO. Both the cancer cell line UMSCC11B and cancer cell line UMSCC38 exhibit strong -H2AX staining, especially following incubation with 20 M HAMNO. Following the addition of HAMNO, both UMSCC38 and OKF4 cells exhibit increased -H2AX staining, with S-phase showing the greatest increase in signal[1].
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| ln Vivo |
HAMNO slows the growth of UMSCC11B tumors in mice. After two hours of treatment with 20 M etoposide, Ser33 of RPA32, an ATR substrate, is heavily phosphorylated. This phosphorylation is reduced with the addition of 2 M HAMNO and is almost absent at higher concentrations, demonstrating an in vivo effect of HAMNO as an inhibitor of RPA32 phosphorylation by ATR[1].
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| Cell Assay |
Cell cycle assessment and γ-H2AX staining are monitored in UMSCC38 and OKF4 cells after 2 h incubation with HAMNO (2, 20, 50 μM) and fixed in 70% ethanol overnight. Cells are washed with PBS and incubated overnight in PBS containing 1% BSA, 10% goat serum and PS139-H2AX antibodies, washed and incubated in goat anti-mouse Alexa Fluor 647 antibody for 30 min at room temperature. Cells are incubated in 50 μg/mL propidium iodide and 100 μg/mL RNase A for 30 min, and 10,000 cells per sample are analyzed[1].
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| Animal Protocol |
In this study, naked thymic mice were used. The tumor cells (2 to 6105 cells in 100 mL of sterile PBS) are subcutaneously injected into 6-week-old female mice to implant UMSCC38 and UMSCC11B cells. Tumor volume [tumor volume=1/2(lengthwidth2)] and vernier calipers are used every day to measure the growth rates of tumors. Etoposide (10 mg/kg mouse) and HAMNO (2 mg/kg) are injected intraperitoneally every day for three days once the tumor has grown to a size of 50 mm3. The volume of the tumor is compared between all experimental groups, and tumor size is tracked daily. Every group includes a minimum of three mice[1].
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| References |
| Molecular Formula |
C17H13NO2
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| Molecular Weight |
263.3
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| Exact Mass |
263.09
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| Elemental Analysis |
C, 77.55; H, 4.98; N, 5.32; O, 12.15
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| CAS # |
138736-73-9
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| Related CAS # |
138736-73-9
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| Appearance |
Solid powder
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| SMILES |
O=C(C=CC1=C/2C=CC=C1)C2=C/NC3=CC=CC=C3O
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| InChi Key |
NADCEWZYITXLKJ-KAMYIIQDSA-N
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| InChi Code |
InChI=1S/C17H13NO2/c19-16-10-9-12-5-1-2-6-13(12)14(16)11-18-15-7-3-4-8-17(15)20/h1-11,18,20H/b14-11-
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| Chemical Name |
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| Synonyms |
HAMNO; CID 6335338; NSC-111847; NSC111847; NSC111847; MLS000737724;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (9.50 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.7979 mL | 18.9897 mL | 37.9795 mL | |
| 5 mM | 0.7596 mL | 3.7979 mL | 7.5959 mL | |
| 10 mM | 0.3798 mL | 1.8990 mL | 3.7979 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Structure/Activity of HAMNO.Cancer Res.2014 Sep 15;74(18):5165-72. |
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Cell-cycle dependent phosphorylation of H2AX generated by HAMNO.Cancer Res.2014 Sep 15;74(18):5165-72. |
HAMNO alters RPA32 and ATR phosphorylation.Cancer Res.2014 Sep 15;74(18):5165-72. |
Additive and synergistic effects of HAMNO with etoposide.Cancer Res.2014 Sep 15;74(18):5165-72. |
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