| Identification | Back Directory | [Name]
Butanoic acid, 4,4'-thiobis-, bis[[(2-hydroxyphenyl)methylene]hydrazide] (9CI) | [CAS]
6325-13-9 | [Synonyms]
Butanoic acid, 4,4'-thiobis-, bis[[(2-hydroxyphenyl)methylene]hydrazide] (9CI) | [Molecular Formula]
C22H26N4O4S | [MOL File]
6325-13-9.mol | [Molecular Weight]
442.53 |
| Hazard Information | Back Directory | [Uses]
Nrf2-IN-3 (Compound R16) is a small-molecule NRF2 inhibitor and increases reactive oxygen species (ROS) production. Nrf2-IN-3 selectively binds KEAP1 mutants and restores their NRF2-inhibitory function by repairing the disrupted KEAP1/NRF2 interactions, leading to proteasome-dependent NRF2 degradation in cells. Nrf2-IN-3 sensitizes KEAP1-mutated tumor cells to Cisplatin (HY-17394), Gefitinib (HY-50895), and KEAP1 G333C-mutated xenograft to Cisplatin [1]. | [in vivo]
Nrf2-IN-3 (110 mg/kg i.p. daily for 5 days per week for six weeks) inhibits tumor growth and selectively sensitizes mKEAP1 A549ctl xenograft to Cisplatin (HY-17394)[1].
| Animal Model: | Palpable tumors were generated by subcutaneous injection of a million A549ctl or A549(WT-KEAP1) cells in the flank of NOD-SCID mice[1].
| | Dosage: | 110 mg/kg for Nrf2-IN-3 and 2 mg/kg for Cisplatin. | | Administration: | Combination of Cisplatin (2 mg/kg) and Nrf2-IN-3 (110 mg/kg). The treatment started on day 18 after subcutaneous injection of A549ctl cells. Mice were treated i.p. with R16 at 110 mg/kg daily for 5 consecutive days per week, Cisplatin at 2 mg/kg twice per week, or the combination of both, or the vehicle | | Result: | Combination of Cisplatin and Nrf2-IN-3 strongly inhibited the growth of A549ctl xenograft, while Cisplatin or Nrf2-IN-3 alone has no effect[1].
Cisplatin alone or in combination with Nrf2-IN-3 significantly inhibited the growth of A549(WT-KEAP1) xenograft, but Nrf2-IN-3 did not significantly enhance the efficacy of cisplatin against this WT-KEAP1 tumor[1].
Cisplatin alone caused slight, but significant, weight loss, Nrf2-IN-3 did not enhance Cisplatin toxicity.
Nrf2-IN-3 alone or in combination with Cisplatin significantly decreased the levels of the NRF2 protein in the A549ctl tumors but not in the A549 (WT-KEAP1) tumors.
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| [References]
[1] Aboulkassim T, et al. A NRF2 inhibitor selectively sensitizes KEAP1 mutant tumor cells to cisplatin and gefitinib by restoring NRF2-inhibitory function of KEAP1 mutants. Cell Rep. 2023 Sep 12;42(9):113104. DOI:10.1016/j.celrep.2023.113104 |
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