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].

RAD51-IN-7 is a potent inhibitor of RAD51, a eukaryotic gene. RAD51-IN-7 has shown research potential for mitochondrial deficiency disorders.

RAD51 Inhibitor B02 (B02) (B02) is an inhibitor of human RAD51 with an IC50 of 27.4 μM.

RAD51-IN-6 is a potent inhibitor of RAD51, which is a eukaryotic gene. RAD51-IN-6 has shown potential for the study of mitochondrial deficiency disorders.

RAD51-IN-4 is a potent RAD51 inhibitor, targeting a eukaryote gene critical for studies on conditions associated with mitochondrial defects.

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

RAD51-IN-3 is a Rad51 inhibitor.

RAD51-IN-5 is a potent inhibitor of RAD51. RAD51-IN-5 has shown potential for the study of mitochondrial deficiency disorders.

RI-1 (RAD51 inhibitor 1) is a RAD51 inhibitor (IC50: 5-30 μM).

Emzadirib (RAD51-IN-2) is a potent RAD51 inhibitor with potential anticancer activity for the study of DNA damage repair.

PU-H71 HCl (Zelavespib HCl) is a novel Hsp90 inhibitor, a novel purine-based analog, and a radiosensitizer that may be a promising agent for CIRT. PU-H71 HCL shows antitumor activity in many preclinical models of malignancy. PU-H71 HCL has an inhibitory effect on the protein expression levels of Rad51 and Ku70, which may be associated with the double chain break repair in the homologous recombination pathway and non-homologous end-joining pathway.

Aromatase inhibitor 23 is an inhibitor that target protein-protein interactions in RAD51 family of recombinases.

D-I03 is a selective RAD52 inhibitor with a Kd of 25.8 µM. D-I03 specifically inhibits RAD52-dependent single-chain annealing (SSA) and D-loop formation, with IC50 of 5 µM and 8 µM, respectively. D-I03 inhibited the growth of BRCA1 and BRCA2 deficient cells and inhibited the formation of damage-induced RAD52 foci, but does not effect on RAD51 foci induced by Cisplatin.

CAM 833 is an effective positivity inhibitor, which can inhibit the interaction between BRCA2 and RAD51. The Kd of ChimRAD51 protein is 366 nM. CAM 833 inhibited the oligocoagulation of RAD51 and promoted the process of apoptosis in G2/M cells.

DIDS, an anion exchange inhibitor, acts by blocking reversibly and later irreversibly, exchangers such as chloride-bicarbonate exchanger. It is also a RAD51 inhibitor.

Amuvatinib (MP470) is an orally bioavailable synthetic carbothioamide with potential antineoplastic activity.

RI-2 is an optimized RAD51 inhibitor with an IC50 of 44.17 μM in the standard DNA binding assay; specifically inhibits HR(Homologous recombination) repair in human cells.

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.

CAM833 is a potent orthosteric inhibitor of the interaction between BRCA2 and RAD51 and also inhibits RAD51 oligomerization and is able to act on the ChimRAD51 protein (Kd: 366 nM).

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].

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.

Halenaquinone is a phosphatidylinositol 3-kinase inhibitor. Halenaquinone specifically inhibits the secondary DNA binding of RAD51. Halenaquinone inhibits RANKL-induced osteoclastogenesis. Halenaquinone induces apoptosis in PC12 cells.

IBR2 (Isoquinoline) is a potent and specific RAD51 inhibitor known for its ability to suppress RAD51-mediated DNA double-strand break repair. By interfering with RAD51 multimerization, accelerating proteasome-mediated RAD51 protein degradation, inhibiting cancer cell growth, and inducing apoptosis, IBR2 has proved to be an effective compound in these aspects.

Bractoppin is a drug-like inhibitor of phosphopeptide recognition by the human BRCA1 tandem (t)BRCT domain (IC50 = 0.074 μM), which selectively inhibits substrate binding with nanomolar potency in vitro. Structure-activity exploration suggests that Bractoppin engages BRCA1 tBRCT residues recognizing pSer in the consensus motif, pSer-Pro-Thr-Phe, plus an abutting hydrophobic pocket that is distinct in structurally related BRCT domains, conferring selectivity.

NSC 617145 (NSC617145) is an inhibitor of WRN helicase that inhibits the ATPase, but not exonuclease, activity of WRN helicase in a concentration-dependent manner.

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.

Amuvatinib hydrochloride (MP470 hydrochloride) is an orally administred multi-targeted tyrosine kinase inhibitor that exhibits strong efficacy against mutant forms of c-Kit, PDGFRα, Flt3, c-Met, and c-Ret, while also acting as a suppressor of DNA repair by inhibiting the RAD51 protein, which is crucial for repairing DNA damage[1][2][3]. This dual mechanism contributes to its antineoplastic activity[4].