rad51-in-1

Rad51-in-1 is a derivative of B02 and an effective inhibitor of Rad51.

BRCA2-RAD51-IN-1, also known as Compound 46, is an inhibitor of BRCA2-RAD51 with an EC50 value of 28 μM, showcasing antitumor properties [1].

HDAC-IN-85 (Compound 1) is an HDAC inhibitor capable of crossing the blood-brain barrier. It exhibits inhibitory effects on brain tumor cell lines and can induce acetylation, resulting in DNA double-strand breaks and promoting RAD51 ubiquitination, which disrupts the DNA repair process. HDAC-IN-85 is applicable in studies of glioblastoma.

RI(dl)-2 TFA is a potent and selective inhibitor of RAD51-mediated D-loop formation, with an IC50 of 11.1 μM, and inhibits homologous recombination (HR) activity in human cells with an IC50 of 3.0 μM [1].

Phosphoramide mustard cyclohexanamine is the active metabolite of cyclophosphamide, an alkylating agent that cross-links DNA strands, organizes cell division and causes cell death, and has antitumor activity.

CAY10760 is an inhibitor of the protein-protein interaction between RAD51 recombinase and BRCA2 (EC50= 19 μM in a cell-free competitive ELISA).1It decreases homologous recombination by 54% in wild-typeBRCA2-expressing BxPC-3 pancreatic cancer cells when used at a concentration of 20 μM. CAY10760 (20 μM) decreases proliferation of BxPC-3, as well as mutantBRCA2-expressing Capan-1, cancer cells when used alone or in combination with the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib . 1.Bagnolini, G., Milano, D., Manerba, M., et al.Synthetic lethality in pancreatic cancer: Discovery of a new RAD51-BRCA2 small molecule disruptor that inhibits homologous recombination and synergizes with olaparibJ. Med. Chem.63(5)2588-2619(2020)

RAD51-IN-8, a new RAD51 binder, is a RAD51-BRCA2 inhibitor that disrupts the RAD51 BRCA2 protein-protein interaction in the micromolar range. This protein-protein interaction (PPI) inhibitor also demonstrates inhibitory activity for H4A4 with an EC50 value of 19 μM [1].

RS-1 is a RAD51 activator. RS-1 also increases CRISPR Cas9-mediated knock-in efficiencies.

NHEJ Inhibitor-1 (Compound C2), a trifunctional Pt(II) complex, mitigates non-homologous end joining (NHEJ) homologous recombination (HR)-related double strand break (DSB) repairs, combating Cisplatin resistance in non-small cell lung cancer (NSCLC). It achieves this by inhibiting the damage repair proteins Ku70 and Rad51, thus re-sensitizing tumors to Cisplatin. Additionally, this compound prompts the generation of reactive oxygen species (ROS) and reduces mitochondrial membrane potential (MMP) [1].

BRC4wt, an acetylated peptide originating from the BRC4 repeat within human BRCA2 (1521-1536), acts as an inhibitor of the BRCA2 and RAD51 protein-protein interaction. When linked to the cationic cell-penetrating peptide (Arg)9, it effectively shortens DNA replication tract lengths and diminishes the frequency of homologous repair of camptothecin-induced DNA damage in vitro. Additionally, BRC4wt enhances the efficacy of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib in inducing cell death in HeLa human cervical cancer and U2OS human osteosarcoma cells, albeit it does not affect non-cancerous hTERT RPE-1, MRC-5, or MCF-10A cells.