Tyrosinemia produced by 2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione (NTBC) in experimental animals and its relationship to corneal injury

The Metabolic Basis of Inherited Disease

(1990) · Annals of Internal Medicine · doi:10.7326/0003-4819-112-5-389_2 · Cited by 3,990 · see citing works

Treatment of hereditary tyrosinaemia type I by inhibition of 4-hydroxyphenylpyruvate dioxygenase

LINDSTEDT, S. (1992) · The Lancet · doi:10.1016/0140-6736(92)92685-9 · Cited by 631 · see citing works

SC‐0051, a 2‐benzoyl‐cyclohexane‐1,3‐dione bleaching herbicide, is a potent inhibitor of the enzyme p‐hydroxyphenylpyruvate dioxygenase

Schulz, A., Ort, O., Beyer, P., & Kleinig, H. (1993) · FEBS Letters · doi:10.1016/0014-5793(93)80013-k · Cited by 192 · see citing works

NONTRANSPLANT TREATMENT OF TYROSINEMIA

Holme, E., & Lindstedt, S. (2000) · Clinics in Liver Disease · doi:10.1016/s1089-3261(05)70142-2 · Cited by 159 · see citing works

Structure of the Ferrous Form of (4-Hydroxyphenyl)pyruvate Dioxygenase from Streptomyces avermitilis in Complex with the Therapeutic Herbicide, NTBC,

Brownlee, J. M., Johnson-Winters, K. L., Harrison, D. H. T., & Moran, G. R. (2004) · Biochemistry · doi:10.1021/bi049317s · Cited by 136 · see citing works

Inhibition of 4-Hydroxyphenylpyruvate Dioxygenase by 2-(2-Nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione and 2-(2-Chloro-4-methanesulfonylbenzoyl)-cyclohexane-1,3-dione

Ellis, M. K., Whitfield, A. C., Gowans, L. A., Auton, T. R., Provan, W. M., Lock, E. A., & Smith, L. L. (1995) · Toxicology and Applied Pharmacology · doi:10.1006/taap.1995.1121 · Cited by 114 · see citing works

Pharmacokinetics and pharmacodynamics of NTBC (2‐(2‐nitro‐4‐fluoromethylbenzoyl)‐1,3‐cyclohexanedione) and mesotrione, inhibitors of 4‐hydroxyphenyl pyruvate dioxygenase (HPPD) following a single dose to healthy male volunteers

Hall, M. G., Wilks, M. F., Provan, W. M., Eksborg, S., & Lumholtz, B. (2001) · British Journal of Clinical Pharmacology · doi:10.1046/j.0306-5251.2001.01421.x · Cited by 110 · see citing works

From toxicological problem to therapeutic use: The discovery of the mode of action of 2‐(2‐nitro‐4‐trifluoromethylbenzoyl)‐1,3‐cyclohexanedione (NTBC), its toxicology and development as a drug

Lock, E. A., Ellis, M. K., Gaskin, P., Robinson, M., Auton, T. R., Provan, W. M., Smith, L. L., Prisbylla, M. P., Mutter, L. C., & Lee, D. L. (1998) · Journal of Inherited Metabolic Disease · doi:10.1023/a:1005458703363 · Cited by 108 · see citing works

THE SOLUBILITY OF THE AMINO ACIDS IN WATER

Dunn, M. S., Ross, F. J., & Read, L. S. (1933) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)75836-5 · Cited by 85 · see citing works

Steady state distribution of free amino acids in the aqueous humours, vitreous body and plasma of the rabbit

Reddy, D. V. N., Rosenberg, C., & Kinsey, V. E. (1961) · Experimental Eye Research · doi:10.1016/s0014-4835(61)80024-9 · Cited by 80 · see citing works

Interaction of (4-Hydroxyphenyl)pyruvate Dioxygenase with the Specific Inhibitor 2-[2-Nitro-4-(trifluoromethyl)benzoyl]-1,3-cyclohexanedione

Kavana, M., & Moran, G. R. (2003) · Biochemistry · doi:10.1021/bi034658b · Cited by 68 · see citing works

Tissue Distribution of 2-(2-Nitro-4-trifluoromethylbenzoyl)cyclohexane-1,3-dione (NTBC): Effect on Enzymes Involved in Tyrosine Catabolism and Relevance to Ocular Toxicity in the Rat

Lock, E. A., Gaskin, P., Ellis, M. K., Provan, W. M., Robinson, M., Smith, L. L., Prisbylla, M. P., & Mutter, L. C. (1996) · Toxicology and Applied Pharmacology · doi:10.1006/taap.1996.0310 · Cited by 52 · see citing works

Ophthalmic follow‐up of patients with tyrosinaemia type I on NTBC

Gissen, P., Preece, M. A., Willshaw, H. A., & McKiernan, P. J. (2003) · Journal of Inherited Metabolic Disease · doi:10.1023/a:1024011110116 · Cited by 49 · see citing works

Richner-Hanhart's Syndrome: Ultrastructural Abnormalities of Epidermal Keratinization Indicating a Causal Relationship to High Intracellular Tyrosine Levels

Bohnert, A., & Anton‐Lamprecht, I. (1982) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12500027 · Cited by 46 · see citing works

Corneal opacities associated with NTBC treatment

Ahmad, S., Teckman, J. H., & Lueder, G. T. (2002) · American Journal of Ophthalmology · doi:10.1016/s0002-9394(02)01532-5 · Cited by 43 · see citing works

Tissue distribution of 2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione (NTBC) and its effect on enzymes involved in tyrosine catabolism in the mouse

Lock, E. A., Gaskin, P., Ellis, M. K., Provan, W. M., Robinson, M., & Smith, L. L. (2000) · Toxicology · doi:10.1016/s0300-483x(99)00205-x · Cited by 33 · see citing works

Spectroscopic and computational studies of NTBC bound to the non-heme iron enzyme (4-hydroxyphenyl)pyruvate dioxygenase: Active site contributions to drug inhibition

Neidig, M. L., Decker, A., Kavana, M., Moran, G. R., & Solomon, E. I. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.08.242 · Cited by 32 · see citing works

[19] 4-Hydroxyphenylpyruvate dioxygenase from human liver

Lindstedt, S., & Odelhög, B. (1987) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(87)42021-1 · Cited by 30 · see citing works

Fluorometric Measurement of Tyrosine in Serum and Plasma

Ambrose, J. A. (1974) · Clinical Chemistry · doi:10.1093/clinchem/20.4.505 · Cited by 29 · see citing works

Crystals in corneal epithelial lesions of tyrosine-fed rats.

Gipson, I. K., Burns, R. P., & Wolfe-Lande, J. D. (1975) · PubMed · Cited by 27 · see citing works

Excess dietary tyrosine and corneal lesions

Rich, L. F., Beard, M. E., & Burns, R. P. (1973) · Experimental Eye Research · doi:10.1016/0014-4835(73)90170-x · Cited by 23 · see citing works

New method for assay of tyrosine transaminase

Schepartz, B. (1969) · Analytical Biochemistry · doi:10.1016/0003-2697(69)90139-0 · Cited by 23 · see citing works

Molecular Biology and Molecular Pathology of a Newly Described Molecular Disease – Tyrosinemia II (The Richner-Hanhart Syndrome)

Goldsmith, L. A. (2008) · Experimental Cell Biology · doi:10.1159/000162885 · Cited by 22 · see citing works

The Effect of a Low-Protein Diet and Dietary Supplementation of Threonine on Tyrosine and 2-(2-Nitro-4-trifluoromethylbenzoyl) cyclohexane-1,3-dione-Induced Corneal Lesions, the Extent of Tyrosinemia, and the Activity of Enzymes Involved in Tyrosine Catabolism in the Rat

Lock, E. A., Gaskin, P., Ellis, M. K., Robinson, M., Provan, W. M., & Smith, L. L. (1998) · Toxicology and Applied Pharmacology · doi:10.1006/taap.1998.8404 · Cited by 19 · see citing works

Conrneal tyrosine crystals in transient neonatal tyrosinemia

Driscoll, D. J., Jabs, E. W., Alcorn, D., Maumenee, I. H., Brusilow, S. W., & Valle, D. L. (1988) · The Journal of Pediatrics · doi:10.1016/s0022-3476(88)80539-0 · Cited by 19 · see citing works

Haemolysis induced by tyrosine crystals: Modifiers and inhibitors

Goldsmith, L. A. (1976) · Biochemical Journal · doi:10.1042/bj1580017 · Cited by 13 · see citing works

Microassay of tyrosine-amino transferase and p-hydroxyphenylpyruvic acid oxidase in mammalian liver and patients with hereditary tyrosinemia

Whelan, D. T., & Zannoni, V. G. (1974) · Biochemical Medicine · doi:10.1016/0006-2944(74)90079-9 · Cited by 10 · see citing works

The Corneal Effects of 2-(2-Nitro-4-Trifluoromethyl-Benzoyl)-Cyclohexane 1,3-Dione (NTBC) in the Rat

Robinson, M. (1995) · Springer eBooks · doi:10.1007/978-1-4615-1887-7_38 · Cited by 9 · see citing works

Perinatal Development of the Tyrosine Oxidizing System

Coufalik, A. H., & Monder, C. (2009) · Biology of the Neonate · doi:10.1159/000241120 · Cited by 9 · see citing works

Corneal organ cultures in tyrosinemia release chemotactic factors.

Lohr, K. M., Hyndiuk, R. A., Dl, H., & Ce, K. (1985) · PubMed · Cited by 2 · see citing works

Recommendations for the management of tyrosinaemia type 1

de Laet, C., Dionisi-Vici, C., Leonard, J. V., McKiernan, P., Mitchell, G., Monti, L., de Baulny, H. O., Pintos-Morell, G., & Spiekerkötter, U. (2013) · Orphanet Journal of Rare Diseases · doi:10.1186/1750-1172-8-8 · Cited by 227 · see citing works

4-Hydroxyphenylpyruvate Dioxygenase and Its Inhibition in Plants and Animals: Small Molecules as Herbicides and Agents for the Treatment of Human Inherited Diseases

Santucci, A., Bernardini, G., Braconi, D., Petricci, E., & Manetti, F. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01395 · Cited by 112 · see citing works

Tyrosine Detoxification Is an Essential Trait in the Life History of Blood-Feeding Arthropods

Sterkel, M., Perdomo, H. D., Guizzo, M. G., Barletta, A. B. F., Nunes, R. D., Dias, F. A., Sorgine, M. H. F., & de Oliveira, P. L. (2016) · Current Biology · doi:10.1016/j.cub.2016.06.025 · Cited by 79 · see citing works

Experience of nitisinone for the pharmacological treatment of hereditary tyrosinaemia type 1

Santra, S., & Baumann, U. (2008) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.9.7.1229 · Cited by 68 · see citing works

Long-Term Outcomes and Practical Considerations in the Pharmacological Management of Tyrosinemia Type 1

van Ginkel, W. G., Rodenburg, I. L., Harding, C. O., Hollak, C. E. M., Heiner-Fokkema, M. R., & van Spronsen, F. J. (2019) · Pediatric Drugs · doi:10.1007/s40272-019-00364-4 · Cited by 58 · see citing works

Nitisinone improves eye and skin pigmentation defects in a mouse model of oculocutaneous albinism

Onojafe, I. F., Adams, D. R., Simeonov, D. R., Zhang, J., Chan, C., Bernardini, I. M., Sergeev, Y. V., Dolinska, M. B., Alur, R. P., Brilliant, M. H., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci59372 · Cited by 57 · see citing works

The Role of Nitisinone in Tyrosine Pathway Disorders

Lock, E. A., Ranganath, L. R., & Timmis, O. G. (2014) · Current Rheumatology Reports · doi:10.1007/s11926-014-0457-0 · Cited by 44 · see citing works

Alkaptonuria – Many questions answered, further challenges beckon

Davison, A. S., Hughes, A., Milan, A. M., Sireau, N. T., Gallagher, J. A., & Ranganath, L. R. (2019) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1177/0004563219879957 · Cited by 36 · see citing works

Asymptomatic Corneal Keratopathy Secondary to Hypertyrosinaemia Following Low Dose Nitisinone and a Literature Review of Tyrosine Keratopathy in Alkaptonuria

Khedr, M., Judd, S., Briggs, M. C., Hughes, A. T., Milan, A. M., Stewart, R. M. K., Lock, E. A., Gallagher, J. A., & Ranganath, L. R. (2017) · JIMD Reports · doi:10.1007/8904_2017_62 · Cited by 28 · see citing works

Nitisinone: a review

Zeybek, A. Ç. A., & Zübarioğlu, T. (2017) · Orphan Drugs Research and Reviews · doi:10.2147/odrr.s92995 · Cited by 28 · see citing works

Inhibition of para‐Hydroxyphenylpyruvate Dioxygenase by Analogues of the Herbicide Nitisinone As a Strategy to Decrease Homogentisic Acid Levels, the Causative Agent of Alkaptonuria

Laschi, M., Bernardini, G., Dreassi, E., Millucci, L., Geminiani, M., Braconi, D., Marzocchi, B., Botta, M., Manetti, F., & Santucci, A. (2016) · ChemMedChem · doi:10.1002/cmdc.201500578 · Cited by 26 · see citing works

Preventive use of nitisinone in alkaptonuria

Wolffenbuttel, B. H. R., Heiner-Fokkema, M. R., & van Spronsen, F. J. (2021) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-021-01977-0 · Cited by 17 · see citing works

The Discovery of the Mode of Action of Nitisinone

Lock, E. A. (2022) · Metabolites · doi:10.3390/metabo12100902 · Cited by 16 · see citing works

Confocal Microscopy of Corneal Crystals in a Patient With Hereditary Tyrosinemia Type I, Treated With NTBC

Schauwvlieghe, P., Jaeken, J., Kestelyn, P., & Claerhout, I. (2012) · Cornea · doi:10.1097/ico.0b013e318243e474 · Cited by 16 · see citing works

Structure-based discovery of pyrazole-benzothiadiazole hybrid as human HPPD inhibitors

Dong, J., Xiao, H., Chen, J., Zheng, B.-F., Xu, Y.-L., Chen, M., Yang, W., Lin, H., & Yang, G. (2023) · Structure · doi:10.1016/j.str.2023.09.005 · Cited by 15 · see citing works

Nonhuman Primate Model of Oculocutaneous Albinism with TYR and OCA2 Mutations

Wu, K., Lv, J., Yang, H., Yang, F., Lin, R., Lin, Q., Shen, R., Wang, J., Duan, W., Hu, M., et al. (2020) · Research · doi:10.34133/2020/1658678 · Cited by 15 · see citing works

Toxicologic Pathology of the Eye: Histologic Preparation and Alterations of the Anterior Segment

Schafer, K. A., & Render, J. A. (2012) · Molecular and integrative toxicology · doi:10.1007/978-1-62703-164-6_5 · Cited by 11 · see citing works

From Weed Killer to Wonder Drug

Lock, E. A. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-55780-9_16 · Cited by 9 · see citing works

Effects of Nitisinone on Oxidative and Inflammatory Markers in Alkaptonuria: Results from SONIA1 and SONIA2 Studies

Braconi, D., Geminiani, M., Psarelli, E. E., Giustarini, D., Marzocchi, B., Rossi, R., Bernardini, G., Spiga, O., Gallagher, J. A., Sang, K. L. Q., et al. (2022) · Cells · doi:10.3390/cells11223668 · Cited by 8 · see citing works

Tyrosinemia type 1: an overview of nursing care.

Barnby, E. (2014) · PubMed · Cited by 8 · see citing works

Species differences and human relevance of the toxicity of 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors and a new approach method in vitro for investigation

Botham, J., Lewis, R. W., Travis, K. Z., Baze, A., Richert, L., Codrea, E., Beninel, G. S., Garcin, J.-C., & Strupp, C. (2023) · Archives of Toxicology · doi:10.1007/s00204-023-03458-8 · Cited by 7 · see citing works

Effects of sulcotrione [2-(2-chloro-4-mesylbenzoyl)-cyclohexane-1,3-dione] on enzymes involved in tyrosine catabolism and the extent of the resulting tyrosinemia and its relationship with corneal lesions in rats

Wu, N., Jin, Y. J., Jin, F., Tan, Y., Tao, H., Zheng, M., Chen, R., Liu, K., & Gao, M. (2010) · Pesticide Biochemistry and Physiology · doi:10.1016/j.pestbp.2010.11.013 · Cited by 7 · see citing works

Novel therapeutics in nystagmus: what has the genetics taught us so far?

Self, J., & Lee, H. (2021) · Therapeutic Advances in Rare Disease · doi:10.1177/2633004021998714 · Cited by 5 · see citing works

Molecular Docking and QSAR Studies for Modeling the Inhibitory Activity of Pyrazole-benzimidazolone Hybrids as Novel Inhibitors of Human 4-hydroxyphenylpyruvate dioxygenase Against Type I Tyrosinemia Disease

(2022) · Biointerface Research in Applied Chemistry · doi:10.33263/briac131.038 · Cited by 4 · see citing works

The β-triketone, nitisinone, kills insecticide-resistant mosquitoes through cuticular uptake

Stavrou–Dowd, Z. T., Parsons, G., Rose, C., Brown, F., Lees, R. S., Acosta-Serrano, Á., & Haines, L. R. (2025) · Parasites & Vectors · doi:10.1186/s13071-025-06939-0 · Cited by 3 · see citing works

Synthesis and Cytotoxicity of Heterocyclic Compounds Derived from Cyclohexane-1,3-Dione

Shaaban, M. A., Kamel, M. M., & Milad, Y. R. (2014) · OALib · doi:10.4236/oalib.1101115 · Cited by 3 · see citing works

A Review of Metabolic Disorder of Amino Acid Tyrosinemia type I: When to Suspect and how to Diagnose

Alobaidy, H. (2017) · IOSR Journal of Pharmacy and Biological Sciences · doi:10.9790/3008-1202015664 · Cited by 1 · see citing works

Use of matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to visualize and support interpretation of toxic effects of 4-hydroxyphenylpyruvate dioxygenase inhibitors in rat tissues

Schneider, R., Giampà, M., Schröder, M., Kubicki, M., Boyken, J., Beuret, L., Beninel, G. S., Niehaus, K., Schorsch, F., Lamshoeft, M., et al. (2025) · Archives of Toxicology · doi:10.1007/s00204-025-04175-0 · Cited by 1 · see citing works

Predicting tyrosinaemia: a mathematical model of 4-hydroxyphenylpyruvate dioxygenase inhibition by nitisinone in rats

Ward, J., Dunster, J. L., Derks, G., Mistry, P., & Salazar, J. D. (2016) · Mathematical Medicine and Biology A Journal of the IMA · doi:10.1093/imammb/dqw006 · Cited by 1 · see citing works

The potential of nitisinone for the treatment of alkaptonuria

Taylor, A. M., & Shepherd, L. (2019) · Expert Opinion on Orphan Drugs · doi:10.1080/21678707.2019.1664899 · Cited by 1 · see citing works

Herbicides

Metruccio, F., Tosti, L., Wilks, M. F., & Moretto, A. (2023) · Patty's Toxicology · doi:10.1002/0471125474.tox137 · Cited by 1 · see citing works

Safety Assessment of Agricultural and Bulk Chemicals

Gröters, S. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-821047-5.00001-4

NTBC dosing and outcomes in hereditary tyrosinemia type 1: insights from a representative human model and 99 patientsPreprint

Pham, Q. T., Tamnanloo, F., M’Callum, M.-A., Beaulieu, E., Mghabghab, R., Théorêt, Y., Mitchell, G. A., the Quebec NTBC Study Group, Cyr, D., Waters, P. J., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.06.680797

Photolyse et oxydation par le chlore et l'ozone de la tembotrione et de la sulcotrione : étude cinétique, identification des produits de transformation et impact sur la toxicité et la biodégradabilité

Tawk, A. (2014) · theses.fr (ABES) · doi:10.70675/3e70364cz26fbz4d26z8827ze3b3950350fe

Plasma and urinary NMR metabolic profiling of the phenylalanine-tyrosine pathway in nitisinone-treated alkaptonuria: comparison of two dosing regimens and identification of a candidate pharmacodynamic biomarker

Grasso, D., Balloni, V., Bianchi, E., Mazzon, A., Bardelli, M., Iacomelli, G., Peruzzi, L., Frediani, B., Santucci, A., & Bernini, A. (2026) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2026.110255

BindingDB Entry 50000919: 4-Hydroxyphenylpyruvate Dioxygenase and Its Inhibition in Plants and Animals: Small Molecules as Herbicides and Agents for the Treatment of Human Inherited Diseases.

BindingDB (2020) · UC San Diego · doi:10.7270/q2fn18nd

Tissue Distribution of 2-(2-Nitro-4-trifluoromethylbenzoyl)cyclohexane-1,3-dione (NTBC): Effect on Enzymes Involved in Tyrosine Catabolism and Relevance to Ocular Toxicity in the Rat

Lock, E. A., Gaskin, P., Ellis, M. K., Provan, W. M., Robinson, M., Smith, L. L., Prisbylla, M. P., & Mutter, L. C. (1996) · Toxicology and Applied Pharmacology · doi:10.1006/taap.1996.0310 · Cited by 52 · see citing works

Tissue distribution of 2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione (NTBC) and its effect on enzymes involved in tyrosine catabolism in the mouse

Lock, E. A., Gaskin, P., Ellis, M. K., Provan, W. M., Robinson, M., & Smith, L. L. (2000) · Toxicology · doi:10.1016/s0300-483x(99)00205-x · Cited by 33 · see citing works

From toxicological problem to therapeutic use: The discovery of the mode of action of 2‐(2‐nitro‐4‐trifluoromethylbenzoyl)‐1,3‐cyclohexanedione (NTBC), its toxicology and development as a drug

Lock, E. A., Ellis, M. K., Gaskin, P., Robinson, M., Auton, T. R., Provan, W. M., Smith, L. L., Prisbylla, M. P., Mutter, L. C., & Lee, D. L. (1998) · Journal of Inherited Metabolic Disease · doi:10.1023/a:1005458703363 · Cited by 108 · see citing works

Inhibition of 4-Hydroxyphenylpyruvate Dioxygenase by 2-(2-Nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione and 2-(2-Chloro-4-methanesulfonylbenzoyl)-cyclohexane-1,3-dione

Ellis, M. K., Whitfield, A. C., Gowans, L. A., Auton, T. R., Provan, W. M., Lock, E. A., & Smith, L. L. (1995) · Toxicology and Applied Pharmacology · doi:10.1006/taap.1995.1121 · Cited by 114 · see citing works

Tyrosinemia I, A Model For Human Diseases Mediated By 2-Oxoacid-Utilizing Dioxygenases: Hepatotoxin Suppression By NTBC Does Not Normalize Hepatic Collagen Metabolism

Hanauske-Abel, H. M., Popowicz, A. M., Remotti, H. E., Newfield, R. S., & Levy, J. F. (2002) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/00005176-200207000-00016 · Cited by 6 · see citing works