BRCA1-IN-1

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

Signaling Pathways >> Cell Cycle/DNA Damage >> PARP

Signaling Pathways >> Epigenetics >> PARP

Research Areas >> Cancer

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].

[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.

Talazoparib | XAV-939 | MK-4827(Niraparib) | Veliparib (ABT-888) | Rucaparib (AG-014699) phosphate | PJ34 HCl | Pamiparib | Rucaparib camsylate | E-7449 | AZD2461 | G007-LK | Iniparib (BSI-201) | NMS-P118 | A-966492 | AG14361