フェンホルミンは7-デヒドロコレステロールレダクターゼの機能阻害を介しコレステロール生合成を抑制することで皮膚黒化を誘導する

1. Sturm, R.A. Molecular genetics of human pigmentation diversity. Hum Mol Genet. 2009, 18, R9–17.

2. Quevedo, W.C.; Holstein, T.J. General biology of mammalian pigmentation. The Pigmentary System. In: Nordlund, J.J.; Boissy, R.E.; Hearing, V.J.; King, R.A.; Oetting, W.S.; Ortonne, J.P. eds), Blackwell Publishing: Oxford, UK, 2006, pp. 63– 90.

3. Costin, G.E.; Hearing, V.J. Human skin pigmentation: melanocytes modulate skin color in response to stress. FASEB J. 2007, 21, 976–994.

4. Halder, R.M.; Nootheti, P.K. Ethnic skin disorders overview. J Am Acad Dermatol. 2003, 48, S143–148.

5. Swinney, D.C.; Anthony, J. How were new medicines discovered? Nat Rev Drug Discov. 2011, 10, 507–519.

6. Murase, D.; Hachiya, A.; Takano, K.; Hicks, R.; Visscher, M.O.; Kitahara, T.; et al. Autophagy has a significant role in determining skin color by regulating melanosome degradation in keratinocytes. J Invest Dermatol. 2013, 133, 2416–2424.

7. Murase, D.; Hachiya, A.; Fullenkamp, R.; Beck, A.; Moriwaki, S.; Hase, T.; et al. Variation in HSP70-1A expression contributes to skin color diversity. J Invest Dermatol. 2016, 136, 1681–1691.

8. Alaimo, P.J.; Shogren-Knaak, M.A.; Shokat, K.M. Chemical genetic approaches for the elucidation of signaling pathways. Curr Opin Chem Biol. 2001, 5, 360–367.

9. Zheng, X.F.; Chan, T.F. Chemical genomics in the global study of protein functions.Drug Discov Today. 2002, 7, 197–205.

10. Schreiber, S.L. The small-molecule approach to biology: Chemical genetics and diversity-oriented organic synthesis make possible the systematic exploration of biology. C&EN. 2003, 81, 51–61.

11. Choi, H.; Kim, J.Y.; Chang, Y.T.; Nam, H.G. Forward chemical genetic screening.Methods Mol Biol. 2014, 1062, 393–404.

12. Hart, C.P. Finding the target after screening the phenotype. Drug Discov Today. 2005, 10, 513–519.

13. Tashiro, E.; Imoto, M. Target identification of bioactive compounds. Bioorg Med Chem. 2012, 20, 1910–1921.

14. Kawatani, M.; Osada, H. Affinity-based identification for bioactive small molecules.Med Chem Commun. 2014, 5, 277–287.

15. Lehraiki, A.; Abbe, P.; Cerezo, M.; Rouaud, F.; Regazzetti, C.; Chignon-Sicard, B; et al. Inhibition of melanogenesis by the antidiabetic metformin. J Invest Dermatol. 2014, 134, 2589–2597.

16. Ando, H.; Niki, Y.; Yoshida, M.; Ito, M.; Akiyama, K.; Kim, J.H.; et al. Keratinocytes in culture accumulate phagocytosed melanosomes in the perinuclear area. Pigment Cell Melanoma Res. 2010, 23, 129–133.

17. Winder, A.J.; Harris, H. New assays for the tyrosin hydroxylase and dopa oxidase activities of tyrosinase. Eur J Biochem. 1991, 198, 317–326.

18. Hachiya, A.; Sriwiriyanont, P.; Kaiho, E.; Kitahara, T.; Takema, Y.; Tsuboi, R. An in vivo mouse model of human skin substitute containing spontaneously sorted melanocytes demonstrates physiological changes after UVB irradiation. J Invest Dermatol. 2005, 125, 364–372.

19. Butterfield, W.J.; Whichelow, M.J. The hypoglycemic action of phenformin. Effect of phenformin on glucose metabolism in peripheral tissues. Diabetes. 1962, 11, 281– 286.

20. Searle, G.L.; Gulli, R. The mechanism of the acute hypoglycemic action of phenformin (DBI). Metabolism. 1980, 29, 630–635.

21. Zhang, L.; He, H.; Balschi, J.A. Metformin and phenformin activate AMP-activated protein kinase in the heart by increasing cytosolic AMP concentration. Am J Physiol Heart Circ Physiol. 2007, 293, H457–466.

22. Theos, A.C.; Truschel, S.T.; Raposo, G.; Marks, M.S. The Silver locus product Pmel17/gp100/Silv/ME20: controversial in name and in function. Pigment Cell Res. 2005, 18, 322–336.

23. del Marmol, V.; Beermann, F. Tyrosinase and related proteins in mammalian pigmentation. FEBS Lett. 1996, 381, 165–168.

24. Sakamoto, S.; Kabe, Y.; Hatakeyama, M.; Yamaguchi, Y.; Handa, H. Development and application of high-performance affinity beads: toward chemical biology and drug discovery. Chem Rec. 2009, 9, 66–85.

25. Tint, G.S.; Irons, M.; Elias, E.R.; Batta, A.K.; Frieden, R.; Chen, T.S.; et al. Defective cholesterol biosynthesis associated with the Smith-Lemli-Opitz syndrome. N Engl J Med. 1994, 330, 107–113.

26. Clémençon, B.; Babot, M.; Trézéguet, V. The mitochondrial ADP/ATP carrier (SLC25 family): pathological implications of its dysfunction. Mol Aspects Med. 2013, 34, 485–493.

27. Pollak, M. Metformin and other biguanides in oncology: advancing the research agenda. Cancer Prev Res. 2010, 3, 1060–1065.

28. Kraml, M.; Bagli, J.F.; Dvornik, D. Inhibition of the conversion of 7- dehydrocholesterol to cholesterol by AY-9944. Biochem Biophys Res Commun. 1964, 15, 455–457.

29. Mizushima, N.; Yoshimori, T. How to interpret LC3 immunoblotting. Autophagy. 2007, 3, 542–545.

30. Wu, N.; Sarna, L.K.; Siow, Y.L.; O, K. Regulation of hepatic cholesterol biosynthesis by berberine during hyperhomocysteinemia. Am J Physiol Regul Integr Comp Physiol. 2011, 300, R635–643.

31. Rena, G.; Pearson, E.R.; Sakamoto, K. Molecular mechanism of action of metformin: old or new insights? Diabetologia. 2013, 56, 1898–1906.

32. Palmieri, F.; Monné, M. Discoveries, metabolic roles and diseases of mitochondrial carriers: A review. Biochim Biophys Acta. 2016, 1863, 2362–2378.

33. Rosand, J.; Friedberg, J.W.; Yang, J.M. Fatal phenformin-associated lactic acidosis.Ann Intern Med. 1997, 127, 170.

34. Dempsey, M.E. Inhibition of lipid biosynthesis. Ann N Y Acad Sci. 1968, 148, 631– 646.

35. Koga, H.; Kaushik, S.; Cuervo, A.M. Altered lipid content inhibits autophagic vesicular fusion. FASEB J. 2010, 24, 3052–3065.

36. Horton, J.D.; Goldstein, J.L.; Brown, M.S. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest. 2002, 109, 1125–1131.

37. Issandou, M.; Guillard, R.; Boullay, A.B.; Linhart, V.; Lopez-Perez, E. Up-regulation of low-density lipoprotein receptor in human hepatocytes is induced by sequestration of free cholesterol in the endosomal/lysosomal compartment. Biochem Pharmacol. 2004, 67, 2281–2289.

38. Tsuruoka, H.; Khovidhunkit, W.; Brown, B.E.; Fluhr, J.W.; Elias, P.M.; Feingold, K.R. Scavenger receptor class B type I is expressed in cultured keratinocytes and epidermis. Regulation in response to changes in cholesterol homeostasis and barrier requirements. J Biol Chem. 2002, 277, 2916–2922.

39. Kinslechner, K.; Schütz, B.; Pistek, M.; Rapolter, P.; Weitzenböck, H.P.; Hundsberger, H.; et al. Loss of SR-BI Down-Regulates MITF and Suppresses Extracellular Vesicle Release in Human Melanoma. Int J Mol Sci. 2019, 20, 1063.

40. Endo, A.; Kuroda, M.; Tanzawa, K. Competitive inhibition of 3-hydroxy-3- methylglutaryl coenzyme A reductase by ML-236A and ML-236B fungal metabolites, having hypocholesterolemic activity. FEBS Lett. 1976, 72, 323–326.

41. Galus, R.; Niderla, J.; Sladowski, D.; Sajjad, E.; Włodarski, K.; Jóźwiak, J. Fluvastatin increases tyrosinase synthesis induced by alpha-melanocyte-stimulating hormone in B16F10 melanoma cells. Pharmacol Rep. 2010, 62, 164–169.

42. Galus, R.; Włodarski, K.; Malejczyk, J.; Jóźwiak, J. Fluvastatin influences hair color in C57BL/6 mice. Int J Mol Sci. 2013, 14, 14333–14345.

43. Lee, J.; Lee, J.; Jung, E.; Cho, J.Y.; Park, D. Artemisinic acid inhibits melanogenesis through downregulation of C/EBP α-dependent expression of HMG-CoA reductase gene. Food Chem Toxicol. 2013, 51, 225–230.

44. Lee, H.J.; Jo, S.Y.; Hwang, J.S.; Chan, S.E. Mevastatin suppresses melanogenesis by lowering the levels of cyclic adenosine monophosphate and cholesterol. Exp Dermatol. 2016, 25, 820–822.

45. Kong, W.; Wei, J.; Abidi, P.; Lin, M.; Inaba, S.; Li, C.; et al. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med. 2004, 10, 1344–1351.

46. Abu, T.M.; Pramod, K.; Ansari, S.H.; Ali, J. Current remedies for vitiligo.Autoimmun Rev. 2010, 9, 516–520.

47. Ali, S.A.; Naaz, I.; Choudhary, R.K. Berberine-induced pigment dispersion in Bufo melanostictus melanophores by stimulation of beta-2 adrenergic receptors. J Recept Signal Transduct Res. 2014, 34, 15–20.