| Description |
GY1-22 is an inhibitor of DNAJA1-mutP53R175H interacting pocket. GY1-22 can be used for the research of cancer[1].
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| Related Catalog |
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| Target |
DNAJA1-mutP53R175H interacting pocket[1]
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| In Vitro |
GY1-22 (0-50 μM; 24 h) 降低小鼠胰腺癌 P03 和人结肠癌 LS123 细胞中突变 p53 蛋白的表达。GY1-22 在 mutp53 驱动的 P03 细胞中抑制 cyclin D1 表达并诱导 wtp53 激活的 Waf1p21 表达[1]。 在 DNAJA1-mutp53 R175H 复合物界面的关键位点发生突变后，GY1-22 失去了降解 mutp53R175H 的能力[1]。 GY1-22 (0-100 μM; 24 h) 在 mutp53 驱动的 P03 胰腺癌细胞中剂量依赖性地抑制细胞生长和显示出低细胞毒性[1]。 Western Blot Analysis[1] Cell Line: Mouse mutp53-driven P03 pancreatic cancer cells and human colon cancer LS123 cells Concentration: 0, 1, 10, 25 and 50 μM Incubation Time: 24 h Result: Reduced mutp53 protein expression in both cells. Exhibited a dose-dependent effect on inhibition of mutp53 and cyclin D1 expression but induction of wtp53-activated Waf1p21 expression tested in P03 cells. Cell Viability Assay[1] Cell Line: Mouse mutp53-driven P03 pancreatic cancer cells Concentration: 0, 25, 50, 75 and 100 μM Incubation Time: 24 h Result: Showed a dose-dependent effect on inhibiting cell growth with IC50 of 28 μM and low cytotoxicity (cell viability).
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| In Vivo |
GY1-22 在大鼠中的 LD50 为 1240 mg/kg。剂量为 10mg /kg (i.p.; daily for 2 weeks) 时对小鼠在大体上或组织学上没有表现出任何毒性[1]。 GY1-22 (1 mg/kg; i.p.; daily for 2 weeks) 在小鼠中抑制 mutp53 驱动的 P03 胰腺癌细胞生长[1]。 Animal Model: C57BL/6J mice implanted with P03 cells[1] Dosage: 1 mg/kg Administration: IP, daily for 2 weeks Result: Showed a significant inhibition of in vivo tumor growth, which was comparable with P03 DNAJA1 knockout line.
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| References |
[1]. Tong X, et al. Identification of a druggable protein-protein interaction site between mutant p53 and its stabilizing chaperone DNAJA1. J Biol Chem. 2021 Jan-Jun;296:100098.
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