brca1-in-2

BRCA1-IN-2 is a cell membrane-crossing BRCA1 protein-protein interaction (PPI) inhibitor with antitumor activity that acts by disrupting the interaction of BRCA1 (BRCT)2 with proteins.

AB25583 is a small molecule inhibitor of Polθ helicase (Polθ-hel) with an IC50 of 6 nM. It selectively kills cells deficient in BRCA1/2 and synergizes with Olaparib in cancer cells harboring pathogenic BRCA1/2 mutations. AB25583 can be utilized in tumor research.

(rac)-Talazoparib ((rac)-BMN-673) (Compound 47) is an orally active inhibitor of PARP1/2, with Ki values of 1.2 nM and 0.87 nM, respectively. It inhibits cellular PARylation at an EC50 of 2.51 nM. This compound leads to the accumulation of DNA damage and suppresses the proliferation of BRCA1/2-mutated MX-1 and Capan-1 cells, with IC50 values of 0.3 nM and 5 nM, respectively. Additionally, (rac)-Talazoparib exhibits antitumor activity in mouse models.

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.

Dicycloplatin is an inducer of DNA damage. It activates doubly phosphorylated checkpoint kinase 2 (CHK2), breast cancer 1 (BRCA1), and triply phosphorylated p53 to induce DNA damage. Dicycloplatin can cause cell cycle arrest, inhibit proliferation, and trigger apoptosis in prostate cancer PC3 cells and lung cancer NCI/H446 cells. It is applicable for research in the field of cancer.

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.

SK-575 is a degradation agent targeting protein-hydrolyzed PARP1 chimera with anticancer and antitumor activity.SK-575 effectively inhibits the growth of cancer cells harboring BRCA1/2 mutations and selectively induces PARP1 degradation in cancer cells.

SC10914 is a highly potent PARP inhibitor (PARP1 IC50 = 7.87 nM) with potent anti-proliferative activity against human BRCA deficient tumor cells (MDA-MB-436, BRCA1 deficient, IC50 = 4.03 nM, Capan-1 BRCA2 deficient, IC50 = 11.66 nM) and PTEN deficient tumor cells (HGC-27,PTEN deficient, IC50 = 0.35 μM). SC10914 showed potent anti-tumor activity in BRCA1/2 mutant tumor models and better pharmacokinetics profile has the potential to be selected as the clinical candidate for the treatment of treatment of BRCA1/2 deficient cancers.

TNG348 is an allosteric, selective, and reversible inhibitor of USP1, causing dose-dependent accumulation of ubiquitinated substrates in vitro and in vivo. CRISPR screens demonstrate that TNG348 disrupts DNA damage tolerance by interfering with the translesion synthesis pathway via RAD18-dependent ubiquitinated PCNA. Although both TNG348 and PARP inhibitors selectively kill homologous recombination-deficient tumors, they act through distinct mechanisms: PARP1 knockout confers resistance to PARP inhibitors but sensitizes cells to TNG348. Consistent with this mechanistic divergence, combining TNG348 with PARP inhibitors results in synergistic antitumor efficacy, including tumor growth inhibition and regression in multiple HRD mouse xenograft models.