STAT5-IN-2 is an orally active STAT5 inhibitor. STAT5-IN-2 effectively blocks the phosphorylation and transcriptional activity of STAT5. STAT5-IN-2 is primarily used in scientific research for leukemia and related tumors, and STAT5-IN-2 inhibits the growth of leukemia cells in a concentration-dependent manner[1].
STAT5-IN-2 (1–10μM) pretreatment of Imatinib-resistant K562R cells, Ara-C-resistant MV4-11R cells, and STAT5BN642Hmutant Ba/F3 cells for 24–48 hours, followed by combined treatment with Imatinib (1μM) or Ara-C (1μM), STAT5-IN-2 significantly inhibits STAT5 phosphorylation and transcriptional activity, induces apoptosis, and overcomes chemotherapy resistance[2].
In vivo, STAT5-IN-2 (10mg/kg) administered intraperitoneally every two days to 6-week-old male C57BL/6 mice for 7 days, STAT5-IN-2 did not produce a significant effect on the number of neutrophils and monocytes/macrophages in the peripheral blood of the mice[3].
References:
[1] Juen L, Brachet-Botineau M, Parmenon C, et al. New Inhibitor Targeting Signal Transducer and Activator of Transcription 5 (STAT5) Signaling in Myeloid Leukemias. J Med Chem. 2017 Jul 27;60(14):6119-6136.
[2] Brachet-Botineau M, Deynoux M, Vallet N, et al. A Novel Inhibitor of STAT5 Signaling Overcomes Chemotherapy Resistance in Myeloid Leukemia Cells. Cancers (Basel). 2019 Dec 17;11(12):2043.
[3] Zhang M, Meng Y, Ying Y, et al. Selective activation of STAT3 and STAT5 dictates the fate of myeloid progenitor cells. Cell Death Discov. 2023 Jul 28;9(1):274.
STAT5-IN-2是一种具有口服活性的STAT5抑制剂。STAT5-IN-2能够有效阻断STAT5的磷酸化和转录活性。STAT5-IN-2主要用于白血病及相关肿瘤的科学研究，STAT5-IN-2能以浓度依赖的方式抑制白血病细胞的生长[1]。
STAT5-IN-2（1–10μM）预处理Imatinib耐药K562R细胞、Ara-C耐药MV4-11R细胞及STAT5BN642H突变Ba/F3细胞24–48h，随后联合Imatinib（1μM）或Ara-C（1μM）处理，STAT5-IN-2显著抑制STAT5磷酸化与转录活性，同时诱导细胞凋亡并克服化疗耐药性[2]。
在体内，STAT5-IN-2（10mg/kg）每两日一次腹腔注射，用于处理6周龄C57BL/6雄性小鼠，持续7天。STAT5-IN-2对小鼠外周血中性粒细胞和单核/巨噬细胞数量未产生显著影响[3]。