Keap1-Nrf2-IN-14 (化合物 20c) 是一种KEAP1-NRF2抑制剂，能有效破坏KEAP1-NRF2相互作用 (IC50=75 nM)，其对KEAP1的Kd值为 24 nM。Keap1-Nrf2-IN-14 能诱导NRF2靶基因的表达并增强下游的抗氧化和抗炎活性。Keap1-Nrf2-IN-14 可用于氧化应激相关炎症的研究。
| 生物活性 | Keap1-Nrf2-IN-14 (compound 20c) is aKEAP1-NRF2inhibitor that effectively disrupts theKEAP1-NRF2interaction (IC50=75 nM) with aKdvalue of 24 nM forKEAP1. Keap1-Nrf2-IN-14 induces the expression ofNRF2target genes and enhances the downstream antioxidant and anti-inflammatory activities. Keap1-Nrf2-IN-14 can be used in the study of oxidative stress-related inflammation[1]. |
| IC50& Target[1] | |
体外研究
(In Vitro) | Keap1-Nrf2-IN-14 effectively activated NRF2-ARE regulated cytoprotective defense system in both concentration- and time- dependent manner in RAW264.7 cells[1].
Keap1-Nrf2-IN-14 (1, 10 μM; 12 h) enhanced the antioxidant capacity in macrophage RAW 264.7 cells[1].
Keap1-Nrf2-IN-14 (1, 10 μM; 12 h) attenuates LPS-induced production of inflammation factors in RAW 264.7 cells[1].
Keap1-Nrf2-IN-14 shows high metabolic stability (in co-incubation with rat liver microsomes with half-life of 10.5 h), and have no CYP inhibition on 1A2, 2C9, 2C19, 2D6 and 3A4 when at 10 μM.
Cell Viability Assay[1] | Cell Line: | RAW264.7 cells (LPS-stimulated) | | Concentration: | 10 μM | | Incubation Time: | 12 h | | Result: | Significantly reduced ROS generation to nearly normal level. |
Cell Viability Assay[1] | Cell Line: | RAW264.7 cells (LPS-stimulated) | | Concentration: | 1, 10 μM | | Incubation Time: | 12 h | | Result: | Notably restored the SOD and GSH-Px levels.
Markedly attenuated the levels of the inflammatory factors IL-1b, IL-6, TNF-a and NO (induced by LPS) in a concentration-dependent manner, and when at 10 μM, almost reduced these cytokines to the basal level. |
RT-PCR[1] | Cell Line: | RAW264.7 cells | | Concentration: | 0.1, 1, 5, 10 μM | | Incubation Time: | 12 h | | Result: | Strongly increased the transcription of NRF2 regulated genes in RAW264.7 cells at a concentration-dependent manner. |
Western Blot Analysis[1] | Cell Line: | RAW264.7 cells | | Concentration: | 10 μM | | Incubation Time: | 1, 2, 4, 8, 16, 24 h | | Result: | Led to nuclear translocation of NRF2 began within 2 h, maximized at 8 h and subsequently declined after 16 h.
Induced NRF2, HO-1, NQO-1 and GCLM protein expression in a time- dependent manner. |
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体内研究
(In Vivo) | Keap1-Nrf2-IN-14 (10 mg/kg; i.p.; single daily for 3 days) reduces the LPS-induced production of the proinflammatory factors in vivo[1].
Keap1-Nrf2-IN-14 (1 mg/kg; i.v.; single) shows half-life of 1.72 h in vivo[1].
| Animal Model: | Female C57BL/6 mice (18-22 g; LPS-induced inflammation model)[1]. | | Dosage: | 10 mg/kg | | Administration: | Intraperitoneal injection; single daily for 3 days. | | Result: | Diminished LPS-induced inflammatory response in vivo. |
| Animal Model: | Female C57BL/6 mice (18-22 g; LPS-induced inflammation model)[1]. | | Dosage: | 1 mg/kg | | Administration: | Intravenous injection; single. | | Result: | Led to half-life of 1.72 h. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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