brca1

BRCA1-IN-1 is a novel small-molecule-like inhibitor of BRCA1 with an IC50 of 0.53 μM and a Ki of 0.71 μM.

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.

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).

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.

Talazoparib (LT-673) is a new-type PARP inhibitor (IC50: 0.58 nM), It similarly binds to PARP1/2 (Kis: 1.2/0.85 nM).

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.

TG2-179-1 is a BRCA1-associated protein 1 (BAP1) inhibitor that effectively hampers BAP1's deubiquitinase activity in cell-free assays at concentrations between 25 µM and 1.5 mM. This compound exhibits cytotoxicity towards a range of eight colon cancer cell lines, with half-maximal inhibitory concentrations (IC50s) spanning from 4.48 to 7.52 µM. Additionally, in an HCT116 colon cancer mouse xenograft model, TG2-179-1 administration at doses of 10 and 30 mg/kg significantly reduces tumor volume, demonstrating its potential in vivo efficacy against colon cancer.

Tumor protein p53 binding protein (53BP1) has been identified in a yeast two-hybrid screen as a protein that interacts with the central DNA–binding domain of p532. Similar to breast cancer susceptibility gene 13, 4 (BRCA1; 53BP1 enhances p53-dependent tra

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].

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.

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.

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.

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.

BAP1-IN-1 is a catalytic activity inhibitor of BRCA1 associated protein 1 (BAP1), exhibiting an inhibitory concentration (IC50) ranging between 0.1-1 μM.

TS-24 is an inhibitor of the cysteine protease histatin S (CTSS).TS-24 promotes BRCA1-mediated apoptosis and shows radiosensitization in a TNBC xenograft mouse model.

PARP1-IN-15 (Compound 6) is a PARP1 inhibitor that also inhibits tankyrase (TNKS) and promotes DNA double-strand breaks, leading to tumor cell apoptosis. It exhibits anti-cancer activity in triple-negative breast cancer (TNBC) cells and patient-derived organoids, making it useful for TNBC research, including cases with or without BRCA1 mutations [1].