BRCA1-IN-1 

BRCA1-IN-1 is a novel small-molecule-like BRCA1 inhibitor with IC₅₀ and K_i of 0.53 μM and 0.71 μM, respecrively.

IC50: 0.53 μM (BRCA1)^[1]
Ki: 0.71 μM (BRCA1)^[1]

BRCTs are phosphoserine-binding domains found in proteins involved in DNA repair, DNA damage response and cell cycle regulation. BRCA1 is a BRCT domain-containing, tumor-suppressing protein expressed in the cells of breast and other tissues. By targeting the (BRCT)₂ domain, BRCA1-IN-1 (Compound 15a) inhibits BRCA1 activities in tumor cells, sensitizes these cells to ionizing radiation-induced apoptosis, and shows synergistic inhibitory effect when used in combination with Olaparib (a small-molecule inhibitor of poly-ADP-ribose polymerase) and Etoposide (a small-molecule inhibitor of topoisomerase II). BRCA1-IN-1 can effectively inhibit HR activity by binding to BRCA1(BRCT)₂, and functionally mimic genetic knockdown of BRCA1. BRCA1-IN-1 is useful in targeting BRCA1/PARP-related pathways involved in DNA damage and repair response, for cancer therapy. The synergistic inhibition of PARP/BRCA1 (a process referred to as synthetic lethality), is highly effective in cancer therapy. BRCA1-IN-1 is small-molecule-like and can be directly administered to tumor cells, thus making them useful for future studies of BRCA1/PARP-related pathways in DNA damage and repair response, and in cancer therapy^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

578.54

C₂₇H₃₃F₂N₄O₆P

1622262-74-1

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Na Z, et al. Discovery of cell-permeable inhibitors that target the BRCT domain of BRCA1 protein by using a small-molecule microarray. Angew Chem Int Ed Engl. 2014 Aug 4;53(32):8421-6.  [Content Brief]