Nitisinone
Tyrosine metabolism inhibitor / Inhibitor of 4-Hydroxyphenylpyruvate dioxygenase (HPPD; IC50 = 40 nM1 and 173 nM2) and is in clinical use for the treatment of hereditary tyrosinemia type 13. CD13+ cancer stem cells (CSCs) are dependent on aerobic metabolism of tyrosine - Nitisinone inhibition of tyrosine metabolism results in lowered availability of acetyl-CoA and fumarate for use in the citric acid cycle causing these CSCs to enter cell cycle, decreasing self-renewal, and making them more susceptible to chemotherapy.4 Nitisinone is a potential treatment option for cancers that rely on tyrosine metabolism.
Biochemicals & reagents
104206-65-7
NTBC
1) Ellis et al. (1995), Inhibition of 4-hydroxy-phenylpyruvate dioxygenase by 2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione and 2-(2-chloro-4-methanesulfonylbenzoyl)-cyclohexane-1,3-dione; Toxicol. Appl. Pharmacol., 133 12 2) Laschi et al. (2016), Inhibition of para-hydroxyphenylpyruvate dioxygenase by analogues of the herbicide nitisinone as a strategy to decrease homogentisic acid levels, the causative agent of alkaptonuria; Chem. Med. Chem., 11 674678 3) McKiernan (2006), Nitisinone in the treatment of hereditary tyrosinaemia type 1; Drugs, 66 743 4) Sun et al. (2020), Activation of Tyrosine Metabolism in CD13+ Cancer Stem Cells Drives Relapse in Hepatocellular Carcinoma; Cancer Res. Treat., 52 604
-20°C
PATHWAY: Amino acid metabolism; Protein synthesis; Cell cycle -- RESEARCH AREA: Cancer stem cells -- DISEASE AREA: Cancer