HAMNO

HAMNO (NSC-111847) is a potent and selective replication protein A (RPA) inhibitor with anti-tumor activity. HAMNO inhibits both ATR autophosphorylation and phosphorylation of RPA32 Ser33 by ATR.

Product information

CAS Number: 138736-73-9

Molecular Weight: 263.29

Formula: C17H13NO2

Synonym:

NSC111847

Chemical Name: (1Z)-1-[(2-Hydroxyanilino)methylidene]naphthalen-2-one

Smiles: OC1=CC=CC=C1N/C=C1\C(=O)C=CC2=CC=CC=C2\1

InChiKey: NADCEWZYITXLKJ-KAMYIIQDSA-N

InChi: 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-

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 50 mg/mL (189.90 mM; Need ultrasonic)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

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 Vivo:

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.

References:

1. Glanzer JG, et al. RPA inhibition increases replication stress and suppresses tumor growth. Cancer Res. 2014 Sep 15;74(18):5165-72.

Products are for research use only. Not for human use.