homologous recombination repair

Fluzoparib (SHR3162) is a novel, potent, and orally available inhibitor of PARP, potentially for the treatment of solid tumours.

AZD-9574 is a selective inhibitor of PARP1 at the sites of SSBs. AZD-9574 exhibits anti-cancer activities and can be used in studies about HRD+ breast cancer and advanced solid malignancies.

Zelpolib is a specific inhibitor of DNA polymerase δ (Pol δ), thereby inhibiting DNA replication and DNA double-strand break homologous recombination repair. It exhibits antiproliferative activity in triple-negative breast cancer cell lines, pancreatic cancer cell lines, and platinum-resistant pancreatic cancer cell lines.

Ran-IN-1 (Compound M36) is an orally active and selective inhibitor of Ran GTPase. It binds allosterically with high specificity to the switch II pocket of GDP-bound Ran (RanGDP), stabilizing its inactive state and reducing the formation of active Ran-GTP. Ran-IN-1 induces apoptosis in epithelial ovarian cancer (EOC) cells and inhibits DNA repair pathways such as homologous recombination (HR) and non-homologous end joining (NHEJ). This compound shows potential for research in epithelial ovarian cancer, particularly in high-grade serous carcinoma.

D-G23 is a selective RAD52 inhibitor. It disrupts RAD52-mediated DNA repair pathways and suppresses the growth of cancer cells deficient in BRCA1 and BRCA2. D-G23 shows promise for research into homologous recombination-related cancers caused by BRCA1/2 mutations, such as hereditary breast and ovarian cancers.

BRCA2-RAD51-IN-2 (compound S-35d) is a BRCA2-RAD51 inhibitor that, when combined with 10 µM Olaparib, can inhibit homologous recombination repair.

PARP-1/Proteasome-IN-1 (compound 42i) is a dual inhibitor of PARP-1 and the proteasome, demonstrating significant inhibitory effects on breast cancer. By downregulating the expression of BRCA1 and RAD51, it impairs homologous recombination repair and induces apoptosis (cellular death).

EXO1-IN-1 (Compound F684) is a potent and selective inhibitor of exonuclease 1 (EXO1) with an IC50 of 15.7 μM. It inhibits DNA end resection, promotes the accumulation of DNA double-strand breaks, and induces S-phase polyadenylation, thereby disrupting DNA repair pathways in homologous recombination-deficient (HRD) cancer cells. This selectivity effectively targets and kills tumor cells with homologous recombination gene defects, such as BRCA1/2 mutations. EXO1-IN-1 holds promise for researching cancers with homologous recombination deficiencies, including BRCA-related tumors.

BER-IN-1 is a base excision repair (BER) inhibitor that specifically targets DNA apurinic/apyrimidinic (abasic) sites. It works by disrupting the BER pathway through β-elimination and β,δ-elimination cleavage at these sites, leading to DNA double-strand breaks (DSBs). BER-IN-1 enhances the effects of the PARP inhibitor Olaparib in cancer cells with normal homologous recombination repair (HR) such as MDA-MB-231, HeLa, and SKOV3. When used in combination with Olaparib, BER-IN-1 can induce S-phase arrest and apoptosis. This compound is utilized in research on cancers, including breast, cervical, and ovarian cancers.

HDAC1-IN-11 (Compound 6) is an HDAC1 inhibitor with an IC50 of 106.6 nM. It suppresses the expression of Sp1 and RAD51, leading to Caspase-dependent apoptosis. HDAC1-IN-11 exhibits antitumor activity and enhances the sensitivity of Etoposide and Gemcitabine by promoting synergistic cell death in NSCLC through inhibiting homologous recombination and non-homologous end joining (NHEJ) pathways involved in DNA double-strand break repair. It is applicable in chemotherapy research for cancers such as NSCLC.

MU876 (Compound 32) is an MUS81 inhibitor with an IC50 of 0.5 μM. It effectively inhibits MUS81-dependent homologous recombination (HR) and break-induced replication (BIR) pathways. MU876 enhances the sensitivity of cancer cells to DNA-damaging agents like Cisplatin by impairing their ability to repair DNA damage. This compound is applicable in cancer chemotherapy research.

HDAC6-IN-63 (Compound 7) is an orally active inhibitor of HDAC6 with an IC50 of 145 nM. It suppresses the expression of Sp1 and RAD51, inducing caspase-dependent apoptosis. HDAC6-IN-63 exhibits antitumor activity and enhances the sensitivity of Etoposide and Gemcitabine by inhibiting homologous recombination and non-homologous end joining (NHEJ) pathways involved in DNA double-strand break (DSB) repair, promoting synergistic cell death in NSCLC cells. This compound is applicable for chemotherapy research in cancers such as NSCLC.

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.

Simmiparib (SMOCL-9112) is a novel and potent PARP1 and PARP2 inhibitor, a derivative of Olaparib.Simmiparib induces DNA double-strand breaks (DSBs) and cell cycle arrest in homologous recombination repair (HR)-deficient cells, thereby contributing to apoptosis.Simmiparib has been used for study Parkinson's disease, Alzheimer's disease, breast cancer, and melanoma.

RECQL5-IN-1 is an orally active RECQL5 inhibitor (IC50 = 46.3 nM) that simultaneously targets both enzymatic and non-enzymatic domains. RECQL5-IN-1 stabilizes the interaction between RECQL5 and RAD51 proteins, disrupting homologous recombination repair (HRR), thereby selectively killing cancer cells that express RECQL5.

MI-223 is an inhibitor of Mcl-1-stimulated homologous recombination (HR) DNA repair, which leads to sensitization of cancer cells to hydroxyurea- or olaparib-induced DNA replication stress.

Zelavespib HCl is a novel Hsp90 inhibitor, a novel purine-based analog, and a radiosensitizer that may be a promising agent for CIRT. Zelavespib HCl shows antitumor activity in many preclinical models of malignancy. Zelavespib 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.

Antitumor agent-81, a P62-RNF168 agonist with low cytotoxicity, enhances the P62-RNF168 interaction, leading to decreased RNF168-mediated H2A ubiquitination and impaired homologous recombination-mediated DNA repair. Additionally, it exhibits dose-dependent inhibition of xenograft tumor growth in mice.

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].

PFM01 is an inhibitor of MRE11 endonuclease. PFM01 can regulate double-strand break repair (DSBR) by nonhomologous end-joining (NHEJ) versus homologous recombination (HR).

KWWCRW is an inhibitory peptide targeting the Holliday junction, exhibiting anticancer activity. It inhibits homologous recombination repair (HDR) during DNA repair by binding to the intermediate structures of the reactive Holliday junction and preventing their resolution. Additionally, KWWCRW inhibits site-specific recombination in vitro in bacteriophages.