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Human sebum requires de novo lipogenesis, which is increased in acne vulgaris and suppressed by acetyl-CoA carboxylase inhibition.
Esler WP, Tesz GJ, Hellerstein MK, Beysen C, Sivamani R, Turner SM, Watkins SM, Amor PA, Carvajal-Gonzalez S, Geoly FJ, Biddle KE, Purkal JJ, Fitch M, Buckeridge C, Silvia AM, Griffith DA, Gorgoglione M, Hassoun L, Bosanac SS, Vera NB, Rolph TP, Pfefferkorn JA, Sonnenberg GE. Esler WP, et al. Among authors: tesz gj. Sci Transl Med. 2019 May 15;11(492):eaau8465. doi: 10.1126/scitranslmed.aau8465. Sci Transl Med. 2019. PMID: 31092695 Clinical Trial.
ACC inhibitor alone or co-administered with a DGAT2 inhibitor in patients with non-alcoholic fatty liver disease: two parallel, placebo-controlled, randomized phase 2a trials.
Calle RA, Amin NB, Carvajal-Gonzalez S, Ross TT, Bergman A, Aggarwal S, Crowley C, Rinaldi A, Mancuso J, Aggarwal N, Somayaji V, Inglot M, Tuthill TA, Kou K, Boucher M, Tesz G, Dullea R, Bence KK, Kim AM, Pfefferkorn JA, Esler WP. Calle RA, et al. Nat Med. 2021 Oct;27(10):1836-1848. doi: 10.1038/s41591-021-01489-1. Epub 2021 Oct 11. Nat Med. 2021. PMID: 34635855 Clinical Trial.
Pharmacologic inhibition of ketohexokinase prevents fructose-induced metabolic dysfunction.
Gutierrez JA, Liu W, Perez S, Xing G, Sonnenberg G, Kou K, Blatnik M, Allen R, Weng Y, Vera NB, Chidsey K, Bergman A, Somayaji V, Crowley C, Clasquin MF, Nigam A, Fulham MA, Erion DM, Ross TT, Esler WP, Magee TV, Pfefferkorn JA, Bence KK, Birnbaum MJ, Tesz GJ. Gutierrez JA, et al. Among authors: tesz gj. Mol Metab. 2021 Jun;48:101196. doi: 10.1016/j.molmet.2021.101196. Epub 2021 Mar 3. Mol Metab. 2021. PMID: 33667726 Free PMC article. Clinical Trial.
Discovery of Fragment-Derived Small Molecules for in Vivo Inhibition of Ketohexokinase (KHK).
Huard K, Ahn K, Amor P, Beebe DA, Borzilleri KA, Chrunyk BA, Coffey SB, Cong Y, Conn EL, Culp JS, Dowling MS, Gorgoglione MF, Gutierrez JA, Knafels JD, Lachapelle EA, Pandit J, Parris KD, Perez S, Pfefferkorn JA, Price DA, Raymer B, Ross TT, Shavnya A, Smith AC, Subashi TA, Tesz GJ, Thuma BA, Tu M, Weaver JD, Weng Y, Withka JM, Xing G, Magee TV. Huard K, et al. Among authors: tesz gj. J Med Chem. 2017 Sep 28;60(18):7835-7849. doi: 10.1021/acs.jmedchem.7b00947. Epub 2017 Sep 11. J Med Chem. 2017. PMID: 28853885
Discovery of PF-06835919: A Potent Inhibitor of Ketohexokinase (KHK) for the Treatment of Metabolic Disorders Driven by the Overconsumption of Fructose.
Futatsugi K, Smith AC, Tu M, Raymer B, Ahn K, Coffey SB, Dowling MS, Fernando DP, Gutierrez JA, Huard K, Jasti J, Kalgutkar AS, Knafels JD, Pandit J, Parris KD, Perez S, Pfefferkorn JA, Price DA, Ryder T, Shavnya A, Stock IA, Tsai AS, Tesz GJ, Thuma BA, Weng Y, Wisniewska HM, Xing G, Zhou J, Magee TV. Futatsugi K, et al. Among authors: tesz gj. J Med Chem. 2020 Nov 25;63(22):13546-13560. doi: 10.1021/acs.jmedchem.0c00944. Epub 2020 Sep 27. J Med Chem. 2020. PMID: 32910646
Discovery of Selective Small Molecule Inhibitors of Monoacylglycerol Acyltransferase 3.
Huard K, Londregan AT, Tesz G, Bahnck KB, Magee TV, Hepworth D, Polivkova J, Coffey SB, Pabst BA, Gosset JR, Nigam A, Kou K, Sun H, Lee K, Herr M, Boehm M, Carpino PA, Goodwin B, Perreault C, Li Q, Jorgensen CC, Tkalcevic GT, Subashi TA, Ahn K. Huard K, et al. J Med Chem. 2015 Sep 24;58(18):7164-72. doi: 10.1021/acs.jmedchem.5b01008. Epub 2015 Sep 8. J Med Chem. 2015. PMID: 26258602
Serine catabolism generates liver NADPH and supports hepatic lipogenesis.
Zhang Z, TeSlaa T, Xu X, Zeng X, Yang L, Xing G, Tesz GJ, Clasquin MF, Rabinowitz JD. Zhang Z, et al. Among authors: tesz gj. Nat Metab. 2021 Dec;3(12):1608-1620. doi: 10.1038/s42255-021-00487-4. Epub 2021 Nov 29. Nat Metab. 2021. PMID: 34845393 Free PMC article.
24 results