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

RAD51-IN-8, a new RAD51 binder, is a RAD51-BRCA2 inhibitor that inhibits the RAD51 BRCA2 protein protein interaction in the micromolar range. RAD51-IN-8 also is a protein protein interaction (PPI) inhibitor. RAD51-IN-8 has inhibitory activity for H4A4 with an EC 50 value of 19 μM [1].

RI(dl)-2 TFA is a potent and selective RAD51-mediated D-loop formation inhibitor with an IC 50 of 11.1 μM which also inhibits homologous recombination(HR) activity in human cells with IC50 of 3.0 μM[1].

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)

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

Phosphoramide mustard cyclohexanamine is the major metabolite for Cyclophosphamide , with anticancer activitiy. Phosphoramide mustard cyclohexanamine induces DNA adduct formation in ovarian granulosa cells, induces DNA damage and elicits the ovarian DNA repair response[1][2]. Phosphoramide mustard cyclohexanamine causes cytotoxicity through forming cross-linked DNA adducts which inhibit DNA strand separation during replication[1].Phosphoramide mustard cyclohexanamine destroys rapidly dividing cells by forming NOR-G-OH, NOR-G and G-NOR-G adducts with DNA, potentially leading to DNA damage[1].Phosphoramide mustard cyclohexanamine (3-6 μM; 48 hours) reduces cell viability in rat spontaneously immortalized granulosa cells (SIGCs)[1].Phosphoramide mustard cyclohexanamine (3-6 μM; 24-48 hours) induces DNA adduct formation[1].Phosphoramide mustard cyclohexanamine (3-6 μM; 24-48 hours) induces ovarian DNA damage in rat ovaries[1].Phosphoramide mustard cyclohexanamine increases DNA damage responses (DDR) gene (Atm, Parp1, Prkdc, Xrcc6, Brca1, Rad51) mRNA expression level[1].Phosphoramide mustard cyclohexanamine (3-6 μM; 24-48 hours) increased DDR proteins[1]. Cell Viability Assay[1] Cell Line: SIGCs Phosphoramide mustard cyclohexanamine (2.1-20.7 mg/kg; i.p.; daily; for 5 days) inhibits subcutaneous tumor growth in rats[2].Phosphoramide mustard cyclohexanamine (86.0 mg/kg; i.v.) has a plasma disappearance half-life of 15.1 minutes[2]. Animal Model: Rat, subcutaneously implanted Walker 256 carcinosarcoma tumor[2] [1]. Shanthi Ganesan, et al. Phosphoramide mustard exposure induces DNA adduct formation and the DNA damage repair response in rat ovarian granulosa cells. Toxicol Appl Pharmacol. 2015 Feb 1; 282(3): 252-258. [2]. S Genka, et al. Brain and plasma pharmacokinetics and anticancer activities of cyclophosphamide and phosphoramide mustard in the rat. Cancer Chemother Pharmacol. 1990;27(1):1-7.

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.

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].