BRCA2

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].

D-I03 is a selective RAD52 inhibitor with a Kd of 25.8 µM. It specifically inhibits RAD52-dependent single-chain annealing (SSA) and D-loop formation, with IC50 values of 5 µM and 8 µM, respectively. D-I03 also inhibits the growth of BRCA1 and BRCA2 deficient cells and prevents the formation of damage-induced RAD52 foci, but does not affect 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.

Carboplatin (JM-8) is a cisplatin derivative, a DNA synthesis inhibitor. Carboplatin binds to DNA, inhibits replication and transcription, and induces cell death. Carboplatin has antitumor activity.

Rucaparib (PF-01367338) is a PARP protein inhibitor (PARP-1 Ki=1.4 nM) and hexose hexose-6-phosphate dehydrogenase (H6PD) inhibitor with oral activity. Rucaparib exhibits antitumor activity, with activity against desmoplasia-resistant prostate cancer (CRPC).

Rucaparib monocamsylate (Rucaparib Camsylate) is a PARP inhibitor (PARP1,Ki of 1.4 nM). Rucaparib Camsylate also displays binding affinity to eight other PARP domains.

PARP1-IN-30 is a specific and effective PARP1 inhibitor with cytotoxic properties. It precisely inhibits PARP1 in tumor cells lacking breast cancer 1 protein (BRCA1) or BRCA2. PARP1-IN-30 holds potential for use in cancer research.

MU147 is an MRE11 nuclease inhibitor and chemical probe with anticancer properties, exhibiting lethal effects on Ehrlich ascites tumor cells both in vivo and in vitro. It disrupts the MRE11 nuclease-dependent double-strand break repair mechanism without impairing ATM activation. Additionally, MU147 damages the degradation of nascent strands at stalled replication forks and selectively affects BRCA2-deficient cells.

MU1409 is an MRE11 nuclease inhibitor with an IC50 of 12.1 μM. It also inhibits FEN1 and EXO1, with IC50 values of 24.2 μM and 176.4 μM, respectively. MU1409 impacts cellular DNA repair and prevents the degradation of stalled replication forks in BRCA2-deficient cells, making it a promising candidate for studying BRCA2 mutation-induced cancers.

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)

Rucaparib Phosphate (PF-01367338 phosphate) is an inhibitor of PARP (Ki: 1.4 nM for PARP1) that is used in clinical therapy to sensitize cancer cells to chemotherapy.

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].

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.

PARP1-IN-14 (compound 19k) is a potent PARP1 inhibitor with an IC50 of 0.6 ± 0.1 nM, displaying antiproliferative effects on MDA-MB-436 (BRCA1 − −) and Capan-1 (BRCA2 − −) cells, with IC50 values below 0.3 nM [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.

BSJ-5-63 is an effective degrader of CDK12, CDK7, and CDK9. It reduces the protein expression of CDK12, CDK7, CDK9, RNAPII, and Cyclin K, and also decreases the mRNA expression of BRCA1 and BRCA2. BSJ-5-63 exhibits anticancer activity and holds potential for prostate cancer research.