| Identification | Back Directory | [Name]
Ethanesulfonamide, N-[6-(6,7-dihydro-1-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-3-yl)-1-(1,1-di-2-pyridinylethyl)-1H-indol-4-yl]- | [CAS]
2344825-52-9 | [Synonyms]
Ethanesulfonamide, N-[6-(6,7-dihydro-1-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-3-yl)-1-(1,1-di-2-pyridinylethyl)-1H-indol-4-yl]- | [Molecular Formula]
C30H28N6O3S | [MOL File]
2344825-52-9.mol | [Molecular Weight]
552.65 |
| Hazard Information | Back Directory | [Description]
XL-223 is a potent BET inhibitor effective in endocrine-resistant ER+ breast cancer with acquired resistance to fulvestrant and palbociclib. XL-223 was more potent in MCF-7:CFR cells than six BET inhibitors in clinical trials. Transcriptomic analysis differentiated XL-223 from the benchmark BETi, JQ-1, showing downregulation of oncogenes and upregulation of tumor suppressors and apoptosis. The therapeutic approach was validated by oral administration of XL-223 in orthotopic xenografts of endocrine-resistant breast cancer in monotherapy and in combination with fulvestrant. Importantly, at an equivalent dose in rats, thrombocytopenia was mitigated. | [Uses]
XP-524 is a potent BET and EP300 inhibitor. XP-524 shows great tumoricidal activity in vivo. XP-524 prevents KRAS-induced, neoplastic transformation in vivo and extends survival in two transgenic mouse models of aggressive PDAC. XP-524 also enhances the presentation of self-peptide and tumor recruitment of cytotoxic T lymphocytes. XP-524 has the potential for the research of pancreatic ductal adenocarcinoma (PDAC)[1]. | [in vivo]
XP-524 (5 mg/kg; i.p.; daily for 150 days) extends survival and inhibits KRAS signaling in uurinePDAC[1].
XP-524 (5 mg/kg; i.p.; daily for 250 days) Cooperates with PD-1 inhibition to further extends survivalin KPC Mice[1]. | Animal Model: | 15 weeks KPC mice[1] | | Dosage: | 5 mg/kg | | Administration: | I.p., daily for 150 days | | Result: | Significantly delayed mortality in KPC mice, extending median survival from 43- to 108-d postenrollment and reduced ERK activation, with parallel reductions in cell prolif-eration and uniform increases in apoptosis. |
| Animal Model: | 15 weeks KPC mice[1] | | Dosage: | 5 mg/kg | | Administration: | I.p.; daily (200-μg dose of anti–PD-1 every other day) for 250 days | | Result: | Increased in cell-mediated cytotoxicity andreduction in T cell exhaustion, the combination of XP-524 andanti–PD-1 enhanced expression of the surrogate marker of cyto-toxicity perforin-1 in tumor-infiltrating CD8+T cell. |
| [References]
[1] Principe DR, et al. XP-524 is a dual-BET/EP300 inhibitor that represses oncogenic KRAS and potentiates immune checkpoint inhibition in pancreatic cancer. Proc Natl Acad Sci U S A. 2022 Jan 25;119(4):e2116764119. DOI:10.1073/pnas.2116764119 |
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