Opportunities and challenges in developing stearoyl-coenzyme A desaturase-1 inhibitors as novel therapeutics for human disease

Journal of Medicinal Chemistry

Volumn 57, Issue 12, 2014, Pages 5039-5056

  Zhang, Zaihui ^a   Dales, Natalie A ^b   Winther, Michael D ^c  

^a Signalchem Lifesciences Corp   (Canada)

^b NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

^c Xenon Pharmaceuticals Inc   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ACYL COENZYME A DESATURASE 1; BIOLOGICAL MARKER; ENZYME INHIBITOR; STEAROYL COENZYME A; STEAROYL COENZYME A DESATURASE 1 INHIBITOR; UNCLASSIFIED DRUG;

ENZYME ACTIVITY; ENZYME INHIBITION; HIGH THROUGHPUT SCREENING; METABOLIC DISORDER; REVIEW;

ANIMALS; HUMANS; LIPID METABOLISM; METABOLIC DISEASES; MOLECULAR TARGETED THERAPY; STEAROYL-COA DESATURASE;

EID: 84903553831     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm401516c     Document Type: Review

References (151)

1. Rask-Andersen, M.; Almén, M. S.; Schiöth, H. B. Trends in the exploitation of novel drug targets Nat. Rev. Drug Discovery 2011, 10, 579-590
2. Mullard, A. Reliability of "new drug target" claims called into question Nat. Rev. Drug Discovery 2011, 10, 643-644
3. Wierzbicki, A. S.; Viljoen, A.; Hardman, T. C.; Mikhailidis, D. P. New therapies to reduce low-density lipoprotein cholesterol Curr. Opin. Cardiol. 2013, 28, 452-457
4. Enoch, H. G.; Catalá, A.; Strittmatter, P. Mechanism of rat liver microsomal stearoyl-CoA desaturase. Studies of the substrate specificity, enzyme-substrate interactions, and the function of lipid J. Biol. Chem. 1976, 251, 5095-5103
5. Spector, A. A.; Yorek, M. A. Membrane lipid composition and cellular function J. Lipid Res. 1985, 26, 1015-1035
6. Jeffcoat, R.; James, A. T. Interrelationship between the dietary regulation of fatty acid synthesis and the fatty acyl-CoA desaturases Lipids 1977, 12, 469-474
7. Gates, A. H.; Karasek, M. Hereditary absence of sebaceous glands in the mouse Science 1965, 148, 1471-1473
8. Zheng, Y.; Eilertsen, K. J.; Ge, L.; Zhang, L.; Sundberg, J. P.; Prouty, S. M.; Stenn, K. S.; Parimoo, S. SCD1 is expressed in sebaceous glands and is disrupted in the asebia mouse Nat. Genet. 1999, 23, 268-270
9. Miyazaki, M.; Kim, Y.-C.; Gray-Keller, M. P.; Attie, A. D.; Ntambi, J. M. The biosynthesis of hepatic cholesterol esters and triglycerides is impaired in mice with a disruption of the gene for stearoyl-CoA desaturase 1 J. Biol. Chem. 2000, 275, 30132-30138
10. Flowers, J. B.; Rabaglia, M. E.; Schueler, K. L.; Flowers, M. T.; Lan, H.; Keller, M. P.; Ntambi, J. M.; Attie, A. D. Loss of stearoyl-CoA desaturase-1 improves insulin sensitivity in lean mice but worsens diabetes in leptin-deficient obese mice Diabetes 2007, 56, 1228-1239
11. Ntambi, J. M.; Miyazaki, M.; Stoehr, J. P.; Lan, H.; Kendziorski, C. M.; Yandell, B. S.; Song, Y.; Cohen, P.; Friedman, J. M.; Attie, A. D. Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 11482-11486
12. Cohen, P.; Miyazaki, M.; Socci, N. D.; Hagge-Greenberg, A.; Liedtke, W.; Soukas, A. A.; Sharma, R.; Hudgins, L. C.; Ntambi, J. M.; Friedman, J. M. Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss Science 2002, 297, 240-243
13. Miyazaki, M.; Sampath, H.; Liu, X.; Flowers, M. T.; Chu, K.; Dobrzyn, A.; Ntambi, J. M. Stearoyl-CoA desaturase-1 deficiency attenuates obesity and insulin resistance in leptin-resistant obese mice Biochem. Biophys. Res. Commun. 2009, 380, 818-822
14. Attie, A. D.; Krauss, R. M.; Gray-Keller, M. P.; Brownlie, A.; Miyazaki, M.; Kastelein, J. J.; Lusis, A. J.; Stalenhoef, A. F. H.; Stoehr, J. P.; Hayden, M. R.; Ntambi, J. M. Relationship between stearoyl-CoA desaturase activity and plasma triglycerides in human and mouse hypertriglyceridemia J. Lipid Res. 2002, 43, 1899-1907
15. Castro, L. F. C.; Wilson, J. M.; Gonçalves, O.; Galante-Oliveira, S.; Rocha, E.; Cunha, I. The evolutionary history of the stearoyl-CoA desaturase gene family in vertebrates BMC Evol. Biol. 2011, 11, 132
16. Sinner, D. I.; Kim, G. J.; Henderson, G. C.; Igal, R. A. StearoylCoA desaturase-5: a novel regulator of neuronal cell proliferation and differentiation PLoS One 2012, 7, 39787
17. Gong, J.; Campos, H.; McGarvey, S.; Wu, Z.; Goldberg, R.; Baylin, A. Genetic variation in stearoyl-CoA desaturase 1 is associated with metabolic syndrome prevalence in Costa Rican adults J. Nutr. 2011, 141, 2211-2218
18. Arregui, M.; Buijsse, B.; Stefan, N.; Corella, D.; Fisher, E.; Di Giuseppe, R.; Coltell, O.; Knüppel, S.; Aleksandrova, K.; Joost, H.-G.; Boeing, H.; Weikert, C. Heterogeneity of the stearoyl-CoA desaturase-1(SCD1) gene and metabolic risk factors in the EPIC-Potsdam study PLoS One 2012, 7, 48338
19. Beiraghi, S.; Zhou, M.; Talmadge, C. B.; Went-Sumegi, N.; Davis, J. R.; Huang, D.; Saal, H.; Seemayer, T. A.; Sumegi, J. Identification and characterization of a novel gene disrupted by a pericentric inversion inv(4)(p13.1q21.1) in a family with cleft lip Gene 2003, 309, 11-21
20. House, R. L.; Cassady, J. P.; Eisen, E. J.; McIntosh, M. K.; Odle, J. Conjugated linoleic acid evokes de-lipidation through the regulation of genes controlling lipid metabolism in adipose and liver tissue Obes. Rev. 2005, 6, 247-258
21. Jeffcoat, R.; Pollard, M. R. Studies on the inhibition of the desaturases by cyclopropenoid fatty acids Lipids 1977, 12, 480-485
22. Jiang, G.; Li, Z.; Liu, F.; Ellsworth, K.; Dallas-Yang, Q.; Wu, M.; Ronan, J.; Esau, C.; Murphy, C.; Szalkowski, D.; Bergeron, R.; Doebber, T.; Zhang, B. B. Prevention of obesity in mice by antisense oligonucleotide inhibitors of stearoyl-CoA desaturase-1 J. Clin. Invest. 2005, 115, 1030-1038
23. Gutiérrez-Juárez, R.; Pocai, A.; Mulas, C.; Ono, H.; Bhanot, S.; Monia, B. P.; Rossetti, L. Critical role of stearoyl-CoA desaturase-1 (SCD1) in the onset of diet-induced hepatic insulin resistance J. Clin. Invest. 2006, 116, 1686-1695
24. Brown, J. M.; Chung, S.; Sawyer, J. K.; Degirolamo, C.; Alger, H. M.; Nguyen, T.; Zhu, X.; Duong, M.-N.; Wibley, A. L.; Shah, R.; Davis, M. A.; Kelley, K.; Wilson, M. D.; Kent, C.; Parks, J. S.; Rudel, L. L. Inhibition of stearoyl-coenzyme A desaturase 1 dissociates insulin resistance and obesity from atherosclerosis Circulation 2008, 118, 1467-1475
25. Jones, P. D.; Holloway, P. W.; Peluffo, R. O.; Wakil, S. J. A requirement for lipids by the microsomal stearyl coenzyme A desaturase J. Biol. Chem. 1969, 244, 744-751
26. Talamo, B. R.; Bloch, K. A new assay for fatty acid desaturation Anal. Biochem. 1969, 29, 300-304
27. Dillon, R.; Greig, M. J.; Bhat, B. G. Development of a novel LC/MS method to quantitate cellular stearoyl-CoA desaturase activity Anal. Chim. Acta 2008, 627, 99-104
28. Tawa, P.; Falgueyret, J.-P.; Guiral, S.; Isabel, E.; Powell, D. A.; Zuck, P.; Skorey, K. High-throughput scintillation proximity assay for stearoyl-CoA desaturase-1 J. Biomol. Screening 2011, 16, 506-517
29. Preparation of nicotinamide derivatives and their use as therapeutic agents for treating stearoyl-CoA desaturase-mediated diseases: Fu, J.-M.; Kodumuru, V.; Sun, S.; Winther, M. D.; Fine, R. M.; Harvey, D. F.; Klebansky, B.; Gray-keller, M. P.; Gschwend, H. W.; Li, W. US 2005/0119251 A1, 2005.
30. Preparation of piperazinylpyridines as inhibitors of human stearoyl CoA desaturase (hSCD): Abreo, M.; Harvey, D. F.; Kondratenko, M. A.; Li, W.; Kamboj, R.; Kodumuru, V.; Winther, M. D.; Gschwend, H. W.; Chakka, N.; Liu, S.; Sviridov, S.; Sun, S. WO 2005/011654 A2, 2005.
31. Preparation of pyridazine derivatives as stearoyl-CoA desaturase inhibitors for the treatment of diabetes and other diseases: Abreo, M.; Chafeev, M.; Chakka, N.; Chowdhury, S.; Fu, J.-M.; Gschwend, H. W.; Holladay, M. W.; Hou, D.; Kamboj, R.; Kodumuru, V.; Li, W.; Liu, S.; Raina, V.; Sun, S.; Sun, S.; Sviridov, S.; Tu, C.; Winther, M. D.; Zhang, Z. WO 2005/011655 A2, 2005.
32. Preparation of piperazinylpyridines as stearoyl-CoA desaturase inhibitors: Abreo, M.; Harvey, D. F.; Gschwend, H. W.; Li, W.; Tu, C.; Kamboj, R.; Winther, M. D.; Kodumuru, V.; Hudson, C. J.; Kondratenko, M. A.; Liu, S.; Raina, V.; Sviridov, S.; Zhang, Z.; Seid, B. M.; Sun, S. WO 2005/011656 A2, 2005.
33. Preparation of pyridazine derivatives as stearoyl-CoA desaturase inhibitors for the treatment of diabetes and other diseases: Abreo, M.; Chafeev, M.; Chakka, N.; Chowdhury, S.; Fu, J.-M.; Gschwend, H. W.; Holladay, M. W.; Hou, D.; Kamboj, R.; Kodumuru, V.; Li, W.; Liu, S.; Raina, V.; Sun, S.; Sun, S.; Sviridov, S.; Tu, C.; Winther, M. D.; Zhang, Z. WO 2005/011655 A2, 2005.
34. Pyridazine derivatives and their use as therapeutic agents in treating stearoyl-CoA desaturase-mediated disease: Gschwend, H. W.; Kodumuru, V.; Liu, S.; Kamboj, R. WO 2005/011653 A2, 2005.
35. Liu, G. Recent advances in stearoyl-CoA desaturase 1 inhibitors for dyslipidemia and obesity Curr. Top. Med. Chem. 2010, 10, 419-433
36. Liu, G. Stearoyl-CoA desaturase 1 (SCD1) inhibitors: bench to bedside must only go through liver RSC Drug Discovery Ser. 2012, 27, 249-269
37. Pyridylpiperazines and aminonicotinamides and their use as therapeutic agents: Gray-Keller, M. P.; Winther, M. D.; Fine, R. M.; Klebansky, B.; Gschwend, H.; Harvey, D. F. US 7,390,813 B1, 2008.
38. Zhang, Z.; Sun, S.; Kodumuru, V.; Hou, D.; Liu, S.; Chakka, N.; Sviridov, S.; Chowdhury, S.; McLaren, D. G.; Ratkay, L. G.; Khakh, K.; Cheng, X.; Gschwend, H. W.; Kamboj, R.; Fu, J.; Winther, M. D. Discovery of piperazin-1-ylpyridazine-based potent and selective stearoyl-CoA desaturase-1 inhibitors for the treatment of obesity and metabolic syndrome J. Med. Chem. 2013, 56, 568-583
39. Meingassner, J. G.; Aschauer, H.; Winiski, A. P.; Dales, N.; Yowe, D.; Winther, M. D.; Zhang, Z.; Stutz, A.; Billich, A. Pharmacological Inhibition of stearoyl CoA desaturase in the skin induces atrophy of the sebaceous glands J. Invest. Dermatol. 2013, 133, 2091-2094
40. Preparation of pyridazinylpiperazinyl trifluorophenyl methanones as stearoyl-CoA desaturase inhibitors: Kamboj, R.; Zhang, Z.; Fu, J.-M.; Kodumuru, V.; Sviridov, S.; Sadalapure, K.; Liu, S.; Sun, S.; Hou, D.; Chakka, N. WO 2006/034440 A2, 2006.
41. Preparation of piperazinylthiadiazole carboxamides as inhibitors of stearoyl-CoA desaturase: Kamboj, R.; Zhang, Z.; Fu, J.-M.; Kodumuru, V.; Liu, S.; Sun, S.; Chakka, N. WO 2008/109840 A1, 2006.
42. Preparation of piperazinylimidazo[1,2- b ]pyridazine-2-carboxamides as inhibitors of stearoyl-CoA desaturase: Kamboj, R.; Fu, J.-M.; Kodumuru, V.; Liu, S.; Sadalapure, K.; Chakka, N.; Hou, D.; Sun, S. WO 2006/034312 A1, 2006.
43. Preparation of piperazinyl benzamide derivatives as stearoyl-CoA desaturase inhibitors: Kamboj, R.; Zhang, Z.; Sviridov, S.; Raina, V.; Hou, D.; Kodumuru, V.; Seid, B. M. WO 2006/034441 A1, 2006.
44. Preparation of bipyridine carboxamide derivatives as inhibitors of stearoyl-CoA desaturase: Kamboj, R.; Zhang, Z.; Fu, J.-M.; Seid, B. M.; Sviridov, S.; Chowdhury, S.; Liu, S.; Kodumuru, V. WO 2006/034279 A1, 2006.
45. Preparation of piperidinylpyridazine carboxamide derivatives as inhibitors of stearoyl-CoA desaturase: Kamboj, R.; Zhang, Z.; Fu, J.-M.; Sviridov, S.; Sun, S.; Seid, B. M.; Raina, V.; Hou, D.; Chowdhury, S.; Liu, S.; Kodumuru, V.; Chakka, N. WO 2006/034338 A1, 2006.
46. Preparation of pyridazine carboxamides as inhibitors of stearoyl-CoA desaturase: Kamboj, R.; Zhang, Z.; Fu, J.-M.; Sviridov, S.; Chowdhury, S.; Kodumuru, V. WO 2006/034341 A2, 2006.
47. Preparation of aminothiazole derivatives as human stearoyl-CoA desaturase inhibitors: Fu, J.; Hou, D.; Kamboj, R.; Kodumuru, V.; Pokrovskaia, N.; Raina, V.; Sun, S.; Sviridov, S.; Zhang, Z. WO 2007/130075 A1, 2007.
48. Heterocyclic compounds as stearoyl-CoA desaturase inhibitors and their preparation, pharmaceutical compositions and use in the treatment of diseases: Dales, N.; Fonarev, J.; Fu, J.; Kamboj, R.; Kodumuru, V.; Liu, S.; Pokrovskaia, N.; Raina, V.; Sun, S.; Zhang, Z. (2008, WO 2008/127349 A2.
49. Preparation of substituted thiazole derivatives for use as stearoyl-CoA desaturase inhibitors: Chowdhury, S.; Dales, N.; Fonarev, J.; Fu, J.; Hou, D.; Jia, Q.; Kodumuru, V.; Pokrovskaia, N.; Sun, S.; Zhang, Z. WO 2009/103739 A1, 2009.
50. Preparation of oxopiperidinylthiazolecarboxamides and related compounds as inhibitors of stearoyl-CoA desaturase (SCD): Dales, N.; Zhang, Z.; Kamboj, R.; Fu, J.; Sun, S.; Pokrovskaia, N.; Sviridov, S. WO 2008/036715 A1. 2008.
51. Sun, S.; Zhang, Z.; Raina, V.; Pokrovskaia, N.; Hou, D.; Namdari, R.; Khakh, K.; Ratkay, L. G.; McLaren, D. G.; Mork, M.; Fu, J.; Ferreira, S.; Hubbard, B.; Winther, M. D.; Dales, N. A. Discovery of thiazolylpyridinone SCD1 inhibitors with preferential liver distribution and reduced mechanism-based adverse effects. Unpublished results.
52. Preparation of thiazole derivatives as stearoyl-CoA desaturase (SCD) inhibitors: Dales, N.; Zhang, Z.; Fonarev, J.; Fu, J.; Kamboj, R.; Kodumuru, V.; Pokrovskaia, N.; Sun, S. WO 2008/074835 A1, 2008.
53. Preparation of heteroarylmethylthiazolecarboxamide derivatives and their use as stearoyl-CoA desaturase inhibitors: Dales, N.; Zhang, Z. WO 2008/024390 A2, 2008.
54. Preparation of isonicotinamide derivatives and analogs for use as stearoyl-CoA desaturase modulators: Dales, N.; Zhang, Z.; Fu, J.; Hou, D.; Sun, S.; Kodumuru, V.; Pokrovskaia, N. WO 2009/156484 A2, 2009.
55. Preparation of spiro derivatives for the modulation of stearoyl-CoA desaturase: Dales, N.; Fonarev, J.; Fu, J.; Zhang, Z. WO 2010/112520 A1, 2010.
56. Preparation of pyrazole derivatives which modulate stearoyl-CoA desaturase: Dales, N.; Fu, J.; Jia, Q.; Pokrovskaia, N.; Sun, S.; Zhang, Z. WO 2011/039358 A1, 2011.
57. Preparation of azacyclohexane derivatives as inhibitors of stearoyl-coenzyme A delta-9 desaturase: Li, C. S.; Ramtohul, Y. K.; Huang, Z.; Lachance, N. WO 2006/130986 A1, 2006.
58. Li, C. S.; Belair, L.; Guay, J.; Murgasva, R.; Sturkenboom, W.; Ramtohul, Y. K.; Zhang, L.; Huang, Z. Thiazole analog as stearoyl-CoA desaturase 1 inhibitor Bioorg. Med. Chem. Lett. 2009, 19, 5214-5217
59. Ramtohul, Y. K.; Black, C.; Chan, C.-C.; Crane, S.; Guay, J.; Guiral, S.; Huang, Z.; Oballa, R.; Xu, L.-J.; Zhang, L.; Li, C. S. SAR and optimization of thiazole analogs as potent stearoyl-CoA desaturase inhibitors Bioorg. Med. Chem. Lett. 2010, 20, 1593-1597
60. Leclerc, J.-P.; Chan, C.-C.; Falgueyret, J.-P.; Guay, J.; Guiral, S.; Huang, Z.; Lachance, N.; Li, C. S.; Oballa, R.; Ramtohul, Y. K.; Zhang, L. SAR of a New Series of Stearoyl-CoA Desaturase Inhibitors. Presented at the 240th National Meeting of the American Chemical Society, Boston, MA, U.S., August 22-26, 2010; MEDI-189.
61. Powell, D. A.; Ramtohul, Y.; Lebrun, M.-E.; Oballa, R.; Bhat, S.; Falgueyret, J.-P.; Guiral, S.; Huang, Z.; Skorey, K.; Tawa, P.; Zhang, L. 2-Aryl benzimidazoles: human SCD1-specific stearoyl coenzyme-A desaturase inhibitors Bioorg. Med. Chem. Lett. 2010, 20, 6366-6369
62. Leger, S.; Black, W. C.; Deschenes, D.; Dolman, S.; Falgueyret, J.-P.; Gagnon, M.; Guiral, S.; Huang, Z.; Guay, J.; Leblanc, Y.; Li, C.-S.; Masse, F.; Oballa, R.; Zhang, L. Synthesis and biological activity of a potent and orally bioavailable SCD inhibitor (MF-438) Bioorg. Med. Chem. Lett. 2010, 20, 499-502
63. Isabel, E.; Powell, D. A.; Black, W. C.; Chan, C.-C.; Crane, S.; Gordon, R.; Guay, J.; Guiral, S.; Huang, Z.; Robichaud, J.; Skorey, K.; Tawa, P.; Xu, L.; Zhang, L.; Oballa, R. Biological activity and preclinical efficacy of azetidinyl pyridazines as potent systemically-distributed stearoyl-CoA desaturase inhibitors Bioorg. Med. Chem. Lett. 2011, 21, 479-483
64. Ramtohul, Y. K.; Powell, D.; Leclerc, J.-P.; Leger, S.; Oballa, R.; Black, C.; Isabel, E.; Li, C. S.; Crane, S.; Robichaud, J.; Guay, J.; Guiral, S.; Zhang, L.; Huang, Z. Bicyclic heteroaryl inhibitors of stearoyl-CoA desaturase: from systemic to liver-targeting inhibitors Bioorg. Med. Chem. Lett. 2011, 21, 5692-5696
65. Zhao, H.; Serby, M. D.; Smith, H. T.; Cao, N.; Suhar, T. S.; Surowy, T. K.; Camp, H. S.; Collins, C. A.; Sham, H. L.; Liu, G. Discovery of 1-(4-phenoxypiperidin-1-yl)-2-arylaminoethanone stearoyl-CoA desaturase 1 inhibitors Bioorg. Med. Chem. Lett. 2007, 17, 3388-3391
66. Liu, G.; Lynch, J. K.; Freeman, J.; Liu, B.; Xin, Z.; Zhao, H.; Serby, M. D.; Kym, P. R.; Suhar, T. S.; Smith, H. T.; Cao, N.; Yang, R.; Janis, R. S.; Krauser, J. A.; Cepa, S. P.; Beno, D. W. A.; Sham, H. L.; Collins, C. A.; Surowy, T. K.; Camp, H. S. Discovery of potent, selective, orally bioavailable stearoyl-CoA desaturase 1 inhibitors J. Med. Chem. 2007, 50, 3086-3100
67. Xin, Z.; Zhao, H.; Serby, M. D.; Liu, B.; Liu, M.; Szczepankiewicz, B. G.; Nelson, L. T. J.; Smith, H. T.; Suhar, T. S.; Janis, R. S.; Cao, N.; Camp, H. S.; Collins, C. A.; Sham, H. L.; Surowy, T. K.; Liu, G. Discovery of piperidine-aryl urea-based stearoyl-CoA desaturase 1 inhibitors Bioorg. Med. Chem. Lett. 2008, 18, 4298-4302
68. Liu, G.; Xin, Z.; Zhao, H.; Serby, M. D.; Smith, H. T.; Cao, N.; Surowy, T. K.; Adler, A.; Mika, A.; Farb, T. B.; Keegan, C.; Landschulz, K.; Brune, M.; Collins, C. A.; Sham, H. L.; Camp, H. S. Stearoyl-CoA Desaturase-1 Inhibitors: Discovery and in Vivo Evaluation. Presented at the 233rd National Meeting of the American Chemical Society, Chicago, IL, U.S., March 25-29, 2007; MEDI-232.
69. Uto, Y.; Ogata, T.; Kiyotsuka, Y.; Ueno, Y.; Miyazawa, Y.; Kurata, H.; Deguchi, T.; Watanabe, N.; Konishi, M.; Okuyama, R.; Kurikawa, N.; Takagi, T.; Wakimoto, S.; Ohsumi, J. Novel benzoylpiperidine-based stearoyl-CoA desaturase-1 inhibitors: identification of 6-[4-(2-methylbenzoyl)piperidin-1-yl]pyridazine- 3-carboxylic acid (2-hydroxy-2-pyridin-3-ylethyl)amide and its plasma triglyceride-lowering effects in Zucker fatty rats Bioorg. Med. Chem. Lett. 2010, 20, 341-345
70. Uto, Y.; Kiyotsuka, Y.; Ueno, Y.; Miyazawa, Y.; Kurata, H.; Ogata, T.; Deguchi, T.; Yamada, M.; Watanabe, N.; Konishi, M.; Kurikawa, N.; Takagi, T.; Wakimoto, S.; Kono, K.; Ohsumi, J. Novel spiropiperidine-based stearoyl-CoA desaturase-1 inhibitors: identification of 1′-{6-[5-(pyridin-3-ylmethyl)- 1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-5-(trifluoromethyl)-3,4- dihydrospiro[chromene-2,4′-piperidine] Bioorg. Med. Chem. Lett. 2010, 20, 746-754
71. Uto, Y.; Ueno, Y.; Kiyotsuka, Y.; Miyazawa, Y.; Kurata, H.; Ogata, T.; Yamada, M.; Deguchi, T.; Konishi, M.; Takagi, T.; Wakimoto, S.; Ohsumi, J. Synthesis and evaluation of novel stearoyl-CoA desaturase 1 inhibitors: 1′-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-3, 4-dihydrospiro[chromene-2,4′-piperidine] analogs Eur. J. Med. Chem. 2010, 45, 4788-4796
72. Uto, Y.; Ueno, Y.; Kiyotsuka, Y.; Miyazawa, Y.; Kurata, H.; Ogata, T.; Takagi, T.; Wakimoto, S.; Ohsumi, J. Discovery of novel SCD1 inhibitors: 5-alkyl-4,5-dihydro-3 H -spiro[1,5-benzoxazepine-2,4′-piperidine] analogs Eur. J. Med. Chem. 2011, 46, 1892-1896
73. Uto, Y.; Ogata, T.; Harada, J.; Kiyotsuka, Y.; Ueno, Y.; Miyazawa, Y.; Kurata, H.; Deguchi, T.; Watanabe, N.; Takagi, T.; Wakimoto, S.; Okuyama, R.; Abe, M.; Kurikawa, N.; Kawamura, S.; Yamato, M.; Osumi, J. Novel and potent inhibitors of stearoyl-CoA desaturase-1. Part I: Discovery of 3-(2-hydroxyethoxy)-4-methoxy- N -[5-(3-trifluoromethylbenzyl)thiazol-2-yl] benzamide Bioorg. Med. Chem. Lett. 2009, 19, 4151-4158
74. Uto, Y.; Ogata, T.; Kiyotsuka, Y.; Miyazawa, Y.; Ueno, Y.; Kurata, H.; Deguchi, T.; Yamada, M.; Watanabe, N.; Takagi, T.; Wakimoto, S.; Okuyama, R.; Konishi, M.; Kurikawa, N.; Kono, K.; Osumi, J. Novel and potent inhibitors of stearoyl-CoA desaturase-1. Part II: Identification of 4-ethylamino-3-(2- hydroxyethoxy)- N -[5-(3-trifluoromethylbenzyl)thiazol-2-yl]benzamide and its biological evaluation Bioorg. Med. Chem. Lett. 2009, 19, 4159-4166
75. Acetylene derivatives as stearoyl CoA desaturase inhibitors and their preparations, pharmaceutical compositions and use in the treatment of diseases: Thomas, A.; Lincam, V. S. P. R.; Phatangare, S. K.; Khairatkar-Joshi, N.; Shah, D. M.; Ukirde, D. V.; More, D. A. WO 2008/062276 A2, 2008.
76. Preparation of oxazolanones as therapeutic stearoyl CoA desaturase inhibitors: Thomas, A.; Lingam, V. S. P. R.; Chaudhari, S. S.; Khairatkar-Joshi, N.; Shah, D. M. WO 2008/029266 A1, 2008.
77. Preparation of spiropiperidine derivatives as stearoyl CoA desaturase inhibitors: Chaudhari, S. S.; Thomas, A.; Gudade, G. B.; Kadam, A.; Patil, N. P.; Khairatkar-Joshi, N.; Shah, D. M. WO 2009/037542 A2, 2009.
78. Preparation of thiazole derivatives as stearoyl CoA desaturase inhibitors: Gharat, L. A.; Narayana, L.; Thomas, A.; Khairatkar-Joshi, N.; Shah, D. M. WO 2010/007482 A2, 2010.
79. Gharat, L. A.; Narayana, L.; Khairatkar-Joshi, N.; Shah, D. IN 2008/MU01420A, 2010.
80. Tissue selective stearoyl-CoA desaturase 1 inhibitors and cell based screening assay for their identification: Khairatkar-Joshi, N.; Shah, D.; Gharat, L. A.; Narayana, L. WO 2010/035052 A1, 2010.
81. Preparation of hexahydropyrrolo[3,4- c ]pyrroles as stearoyl CoA desaturase inhibitors: Zoller, G.; Voss, M. D.; Keil, S.; Herling, A.; Matter, H. WO 2008/135141 A1, 2008.
82. Preparation of 2-heteroarylpyrrolo[3,4- c ]pyrroles as stearoyl CoA desaturase (SCD) inhibitors: Zoller, G.; Voss, M. D.; Matter, H.; Herling, A. WO 2010/028761 A1, 2010.
83. Azoloraine derivatives, method for the production thereof, pharmaceuticals containing these compounds, and the use thereof: Zoller, G.; Voss, M. D.; Matter, H.; Herling, A.; Philippo, C.; Namane, C.; Sanchez-Arias, J.-A. WO 2009/024287 A2, 2009.
84. Voss, M. D.; Zoller, G.; Matter, H.; Herling, A. W.; Biemer-Daub, G.; Pfenninger, A.; Haag-Diergarten, S.; Keil, S.; Kohlmann, M.; Schmidts, H.-L. Discovery and pharmacological characterization of SAR707 as novel and selective small molecule inhibitor of stearoyl-CoA desaturase (SCD1) Eur. J. Pharmacol. 2013, 707, 140-146
85. Matter, H.; Zoller, G.; Herling, A. W.; Sanchez-Arias, J.-A.; Philippo, C.; Namane, C.; Kohlmann, M.; Pfenninger, A.; Voss, M. D. Benzimidazole- carboxamides as potent and bioavailable stearoyl-CoA desaturase (SCD1) inhibitors from ligand-based virtual screening and chemical optimization Bioorg. Med. Chem. Lett. 2013, 23, 1817-1822
86. Novel piperazine derivatives as inhibitors of stearoyl-CoA desaturase and their preparation and use in the treatment of obesity and diabetes: Bischoff, A.; Subramanya, H. S.; Sundaresan, K.; Sammeta, S. R.; Vaka, A. K. WO 2008/157844 A1, 2008.
87. Preparation of piperazine derivatives for use as stearoyl-CoA desaturase inhibitors: Bischoff, A.; Raikar, S. N.; Sammeta, S. R.; Prabhu, G.; Subramanya, H.; Sundaresan, K. WO 2009/117659 A1, 2009.
88. Preparation of piperidine derivatives and analogs for use as stearoyl-CoA desaturase inhibitors: Bischoff, A.; Sundaresan, K.; Koteswara, R.; Bala, P.; Ainan, B.; Ayyamperumal, H.; A.R, G.; Tatiparthy, S.; Prabhu, G.; Subramanya, H. WO 2009/117676 A2, 2009.
89. Preparation of piperazine derivatives as inhibitors of stearoyl-CoA desaturase: Bischoff, A.; Subramanya, H.; Sundaresan, K.; Sammeta, S. R.; Vaka, A. K. US 2010/0160323 A1, 2010.
90. Bouillot, A. M. J.; Daugan, A. C.-M.; Dean, A. W.; Fillmore, M. C. WO 2008/074832 A2, 2008.
91. Preparation of substituted 1,6-naphthyridines as SCD inhibitors: Daugan, A. C.-M. WO 2009/056556 A1, 2009.
92. Preparation of pyrazole derivatives and use thereof as inhibitors of stearoyl-CoA desaturase: Daugan, A. C.-M. WO 2009/010560 A1, 2009.
93. Preparation of N-thiazolyl-1,2,3,4-tetrahydro-6-isoquinolinecarboxamide derivatives as therapeutic inhibitors of stearoyl coenzyme A desaturase (SCD): Daugan, A. C.-M.; Dean, A. W.; Fillmore, M. C. WO 2009/150196 A1, 2009.
94. Triazole derivatives as SCD inhibitors and their preparation, pharmaceutical compositions and use in the treatment of SCD-mediated diseases: Bouillot, A. M. J.; Laroze, A. WO 2009/060054 A1, 2009.
95. Preparation of triazole derivatives as SCD inhibitors: Bouillot, A. M. J. WO 2009/016216 A1, 2009.
96. 1,2,3-Triazole derivatives for use as stearoyl-CoA desaturase inhibitors and their preparation, pharmaceutical compositions and use in the treatment of SCD-mediated diseases: Bouillot, A. M. J.; Laroze, A.; Trottet, L. WO 2009/060053 A1, 2009.
97. Preparation of thiadiazole derivatives as inhibitors of stearoyl-CoA desaturase: Bouillot, A. M. J.; Boyer, T.; Daugan, A. C.-M.; Dean, A. W.; Fillmore, M. C.; Lamotte, Y. WO 2008/104524 A1, 2008.
98. Issandou, M.; Bouillot, A.; Brusq, J.-M.; Forest, M.-C.; Grillot, D.; Guillard, R.; Martin, S.; Michiels, C.; Sulpice, T.; Daugan, A. Pharmacological inhibition of stearoyl-CoA desaturase 1 improves insulin sensitivity in insulin-resistant rat models Eur. J. Pharmacol. 2009, 618, 28-36
99. Koltun, D. O.; Parkhill, E. Q.; Vasilevich, N. I.; Glushkov, A. I.; Zilbershtein, T. M.; Ivanov, A. V.; Cole, A. G.; Henderson, I.; Zautke, N. A.; Brunn, S. A.; Mollova, N.; Leung, K.; Chisholm, J. W.; Zablocki, J. Novel, potent, selective, and metabolically stable stearoyl-CoA desaturase (SCD) inhibitors Bioorg. Med. Chem. Lett. 2009, 19, 2048-2052
100. Pteridinone derivatives for use as stearoyl CoA desaturase inhibitors: Zilbershtein, T.; Cole, A.; Zablocki, J.; Koltun, D.; Chisholm, J.; Glushkov, A.; Vasilevich, N.; Henderson, I.; Lin, T.; Parkhill, E. WO 2008/123891 A1, 2008.
101. Koltun, D. O.; Vasilevich, N. I.; Parkhill, E. Q.; Glushkov, A. I.; Zilbershtein, T. M.; Mayboroda, E. I.; Boze, M. A.; Cole, A. G.; Henderson, I.; Zautke, N. A.; Brunn, S. A.; Chu, N.; Hao, J.; Mollova, N.; Leung, K.; Chisholm, J. W.; Zablocki, J. Orally bioavailable, liver-selective stearoyl-CoA desaturase (SCD) inhibitors Bioorg. Med. Chem. Lett. 2009, 19, 3050-3053
102. 3-Hydroquinazolin-4-one derivatives, and their preparation and use as inhibitors of stearoyl-CoA desaturase (SCD): Glushkov, A.; Koltun, D.; Mayboroda, E.; Parkhill, E.; Vasilvevich, N.; Zablocki, J. WO 2010/045374 A1, 2010.
103. 3-Hydroquinazolin-4-one derivatives as stearoyl-CoA desaturase inhibitors and their preparation and use for the treatment of diseases: Koltun, D.; Parkhill, E.; Boze, M.; Zablocki, J.; Vasilevich, N.; Mayboroda, E.; Glushkov, A.; Cole, A.; Chisholm, J. WO 2010/056230 A1, 2010.
104. Koltun, D. O.; Zilbershtein, T. M.; Migulin, V. A.; Vasilevich, N. I.; Parkhill, E. Q.; Glushkov, A. I.; McGregor, M. J.; Brunn, S. A.; Chu, N.; Hao, J.; Mollova, N.; Leung, K.; Chisholm, J. W.; Zablocki, J. Potent, orally bioavailable, liver-selective stearoyl-CoA desaturase (SCD) inhibitors Bioorg. Med. Chem. Lett. 2009, 19, 4070-4074
105. Preparation of five-membered heterocyclic carboxamides as stearoyl-CoA desaturase 1 (SCD1) inhibitors: Iida, T.; Ubukata, M.; Mitani, I.; Nakagawa, Y.; Tanaka, M. WO 2008/120744 A1, 2008.
106. Preparation of N -aryl- or N -heterocyclylpyrrolidine-1-carboxamides or -piperidine-1-carboxamides having substituted urea structure as inhibitors of stearoyl-CoA desaturase 1 (SCD1) inhibitors: Ubukata, M.; Maeda, K.; Iida, T.; Mitani, I. WO 2008/120759 A1, 2008.
107. Preparation of six-membered heterocyclic amide and benzamide derivatives as stearoyl-CoA desaturase 1 (SCD1) inhibitors: Iida, T.; Mitani, I.; Nakagawa, Y.; Tanaka, M. WO 2008/123469 A1, 2008.
108. Derivatives of triazines and uracils, their preparation and their use as SCD-1 inhibitors: Leroy, I.; Dupont-Passelaigue, E.; Valeille, K.; Rival, Y.; Junquero, D. WO 2010/006962 A1, 2010.
109. Derivatives of 2 H -pyridazin-3-ones, their preparation and their use as SCD-1 inhibitors: Dupont-Passelaigue, E.; Mialhe, S.; Rieu, J.-P.; Junquero, D.; Valeille, K. WO 2011/015629 A1, 2011.
110. Derivatives of nitrogen heterocycles, their preparation and their use as SCD-1 inhibitors in pharmaceutical and cosmetic compositions: Leroy, I.; Dupont-Passelaigue, E.; Mialhe, S.; Junquero, D.; Valeille, K. WO 2011/131593 A1, 2011.
111. Preparation of aromatic amine derivatives as stearoyl-CoA desaturase (SCD) inhibitors: Taniguchi, T.; Miyata, K.; Kubo, O.; Matsui, J. WO 2008/044767 A1, 2008.
112. Preparation of pyridazine ring-containing spiro compounds as stearoyl-CoA desaturase inhibitors for treatment of obesity, diabetes, etc.: Taniguchi, T.; Miyata, K.; Kubo, O. WO 2008/096746 A1, 2008.
113. Atkinson, K. A.; Beretta, E. E.; Brown, J. A.; Castrodad, M.; Chen, Y.; Cosgrove, J. M.; Du, P.; Litchfield, J.; Makowski, M.; Martin, K.; McLellan, T. J.; Neagu, C.; Perry, D. A.; Piotrowski, D. W.; Steppan, C. M.; Trilles, R. N -Benzylimidazole carboxamides as potent, orally active stearoylCoA desaturase-1 inhibitors Bioorg. Med. Chem. Lett. 2011, 21, 1621-1625
114. Preparation of (S)-2-[4-(hydroxymethyl)phenoxy]-1-[3-[2-(trifluoromethyl) phenoxy]pyrrolidin-1-yl]ethanone as a stearoyl-CoA desaturase (SCD1) inhibitor: Li, J.; Kolosko, N. L. WO 2009/019566 A1, 2009.
115. Preparation of benzylpiperazinylpyrimidones as inhibitors of stearoyl-CoA desaturase (SCD1): Gillespie, P.; Goodnow, R. A., Jr.; Erickson, S. D.; Jones, R. US 2009/0149466 A1, 2009.
116. Preparation of pyrazolo[1,5- a ]pyrimidines as inhibitors of stearoyl-CoA desaturase: Bremberg, U.; Linden, A.; Lundbaeck, T.; Nilsson, J.; Wiik, M.; Bergner, M.; Brandt, P.; Hammer, K.; Ringom, R. WO 2008/116898 A1, 2008.
117. Preparation of pyrazolo[1,5- a ]pyrimidine derivatives for use as inhibitors of stearoyl-CoA desaturase (SCD) activity: Lundbaeck, T.; Climent-Johansson, I.; Vaagberg, J.; Bremberg, U.; Linden, A.; Nilsson, J.; Wiik, M. WO 2008/003753 A1, 2008.
118. Preparation of piperazine derivatives as inhibitors of stearoyl-CoA-desaturase-1 enzyme: Fajas, L.; Benfodda, Z.; Fritz, V. WO 2011/030312 A1, 2011.
119. Kalliokoski, A.; Niemi, M. Impact of OATP transporters on pharmacokinetics Br. J. Pharmacol. 2009, 158, 693-705
120. Oballa, R. M.; Belair, L.; Black, W. C.; Bleasby, K.; Chan, C. C.; Desroches, C.; Du, X.; Gordon, R.; Guay, J.; Guiral, S.; Hafey, M. J.; Hamelin, E.; Huang, Z.; Kennedy, B.; Lachance, N.; Landry, F.; Li, C. S.; Mancini, J.; Normandin, D.; Pocai, A.; Powell, D. A.; Ramtohul, Y. K.; Skorey, K.; Sorensen, D.; Sturkenboom, W.; Styhler, A.; Waddleton, D. M.; Wang, H.; Wong, S.; Xu, L.; Zhang, L. Development of a liver-targeted stearoyl-CoA desaturase (SCD) inhibitor (MK-8245) to establish a therapeutic window for the treatment of diabetes and dyslipidemia J. Med. Chem. 2011, 54, 5082-5096
121. Powell, D. A.; Black, W. C.; Bleasby, K.; Chan, C.-C.; Deschenes, D.; Gagnon, M.; Gordon, R.; Guay, J.; Guiral, S.; Hafey, M. J.; Huang, Z.; Isabel, E.; Leblanc, Y.; Styhler, A.; Xu, L.-J.; Zhang, L.; Oballa, R. M. Nicotinic acids: liver-targeted SCD inhibitors with preclinical anti-diabetic efficacy Bioorg. Med. Chem. Lett. 2011, 21, 7281-7286
122. Lachance, N.; Guiral, S.; Huang, Z.; Leclerc, J.-P.; Li, C. S.; Oballa, R. M.; Ramtohul, Y. K.; Wang, H.; Wu, J.; Zhang, L. Discovery of potent and liver-selective stearoyl-CoA desaturase (SCD) inhibitors in an acyclic linker series Bioorg. Med. Chem. Lett. 2012, 22, 623-627
123. Lachance, N.; Gareau, Y.; Guiral, S.; Huang, Z.; Isabel, E.; Leclerc, J.-P.; Leger, S.; Martins, E.; Nadeau, C.; Oballa, R. M.; Ouellet, S. G.; Powell, D. A.; Ramtohul, Y. K.; Tranmer, G. K.; Trinh, T.; Wang, H.; Zhang, L. Discovery of potent and liver-targeted stearoyl-CoA desaturase (SCD) inhibitors in a bispyrrolidine series Bioorg. Med. Chem. Lett. 2012, 22, 980-984
124. Spirocyclic oxazepine compounds as stearoyl-coenzyme A DELTA-9 desaturase inhibitors: Shipps, G. W., Jr.; Yang, Z.; West, R. WO 2011/011506 A1, 2011.
125. Preparation of 4,5-dihydro-3 H -spiro[benzo[ b ][1,4]oxazepine-2, 4′-piperidine] derivatives as stearoyl-CoA delta-9 desaturase inhibitors: Shipps, G. W., Jr.; Yang, Z.; Deng, Y.; West, R.; Sinha, D. P. WO 2011/011508 A1, 2011.
126. Deng, Y.; Yang, Z.; Shipps, G. W.; Lo, S.-M.; West, R.; Hwa, J.; Zheng, S.; Farley, C.; Lachowicz, J.; van Heek, M.; Bass, A. S.; Sinha, D. P.; Mahon, C. R.; Cartwright, M. E. Discovery of liver-targeted inhibitors of stearoyl-CoA desaturase (SCD1) Bioorg. Med. Chem. Lett. 2013, 23, 791-796
127. Brown, J. M.; Rudel, L. L. Stearoyl-coenzyme A desaturase 1 inhibition and the metabolic syndrome: considerations for future drug discovery Curr. Opin. Lipidol. 2010, 21, 192-197
128. Flowers, M. T.; Ade, L.; Strable, M. S.; Ntambi, J. M. Combined deletion of SCD1 from adipose tissue and liver does not protect mice from obesity J. Lipid Res. 2012, 53, 1646-1653
129. Zouboulis, C. C. Acne and sebaceous gland function Clin. Dermatol. 2004, 22, 360-366
130. Janiczek-Dolphin, N.; Cook, J.; Thiboutot, D.; Harness, J.; Clucas, A. Can sebum reduction predict acne outcome? Br. J. Dermatol. 2010, 163, 683-688
131. Igal, R. A. Stearoyl-CoA desaturase-1: a novel key player in the mechanisms of cell proliferation, programmed cell death and transformation to cancer Carcinogenesis 2010, 31, 1509-1515
132. Igal, R. A. Roles of stearoyl-CoA desaturase-1 in the regulation of cancer cell growth, survival and tumorigenesis Cancers 2011, 3, 2462-2477
133. Scaglia, N.; Igal, R. A. Inhibition of stearoyl-CoA desaturase 1 expression in human lung adenocarcinoma cells impairs tumorigenesis Int. J. Oncol. 2008, 33, 839-850
134. Methods using stearoyl-CoA desaturase 1 (SCD1) antagonists for treatment of cancer: Ashkenazi, A.; Du, X.; Qing, J. WO 2013/056148 A2, 2013.
135. Mason, P.; Liang, B.; Li, L.; Fremgen, T.; Murphy, E.; Quinn, A.; Madden, S. L.; Biemann, H.-P.; Wang, B.; Cohen, A.; Komarnitsky, S.; Jancsics, K.; Hirth, B.; Cooper, C. G. F.; Lee, E.; Wilson, S.; Krumbholz, R.; Schmid, S.; Xiang, Y.; Booker, M.; Lillie, J.; Carter, K. SCD1 inhibition causes cancer cell death by depleting mono-unsaturated fatty acids PLoS One 2012, 7, 33823
136. Mauvoisin, D.; Charfi, C.; Lounis, A. M.; Rassart, E.; Mounier, C. Decreasing stearoyl-CoA desaturase-1 expression inhibits β-catenin signaling in breast cancer cells Cancer Sci. 2013, 104, 36-42
137. Von Roemeling, C. A.; Marlow, L. A.; Wei, J. J.; Cooper, S. J.; Caulfield, T. R.; Wu, K.; Tan, W. W.; Tun, H. W.; Copland, J. A. Stearoyl-CoA desaturase 1 is a novel molecular therapeutic target for clear cell renal cell carcinoma Clin. Cancer Res. 2013, 19, 2368-2380
138. Gao, H.; Feng, Y.; Zhu, J.; He, X.; Lu, P.; Liu, H. Down-regulation of stearoyl-CoA desaturase 1 expression inhibits cell proliferation and induces apoptosis of esophageal squamous cell carcinoma and their related molecular mechanism Zhongliu 2012, 32, 681-688
139. Scaglia, N.; Chisholm, J. W.; Igal, R. A. Inhibition of stearoylCoA desaturase-1 inactivates acetyl-CoA carboxylase and impairs proliferation in cancer cells: role of AMPK PLoS One 2009, 4 (8 e6812
140. Nashed, M.; Chisholm, J. W.; Igal, R. A. Stearoyl-CoA desaturase activity modulates the activation of epidermal growth factor receptor in human lung cancer cells Exp. Biol. Med. 2012, 237, 1007-1017
141. Holder, A.; Gonzalez-Angulo, A.; Chen, H.; Akcakanat, A.; Do, K.-A.; Fraser Symmans, W.; Pusztai, L.; Hortobagyi, G.; Mills, G.; Meric-Bernstam, F. High stearoyl-CoA desaturase 1 expression is associated with shorter survival in breast cancer patients Breast Cancer Res. Treat. 2013, 137, 319-327
142. Fritz, V.; Benfodda, Z.; Rodier, G.; Henriquet, C.; Iborra, F.; Avancès, C.; Allory, Y.; De la Taille, A.; Culine, S.; Blancou, H.; Cristol, J. P.; Michel, F.; Sardet, C.; Fajas, L. Abrogation of de novo lipogenesis by stearoyl-CoA desaturase 1 inhibition interferes with oncogenic signaling and blocks prostate cancer progression in mice Mol. Cancer Ther. 2010, 9, 1740-1754
143. Chajes, V.; Joulin, V.; Clavel-Chapelon, F. The fatty acid desaturation index of blood lipids, as a biomarker of hepatic stearoyl-CoA desaturase expression, is a predictive factor of breast cancer risk Curr. Opin. Lipidol. 2011, 22, 6-10
144. Minville-Walz, M.; Pierre, A.-S.; Pichon, L.; Bellenger, S.; Fevre, C.; Bellenger, J.; Tessier, C.; Narce, M.; Rialland, M. Inhibition of stearoyl-CoA desaturase 1 expression induces CHOP-dependent cell death in human cancer cells PLoS One 2010, 5, e14363
145. Roongta, U. V.; Pabalan, J. G.; Wang, X.; Ryseck, R.-P.; Fargnoli, J.; Henley, B. J.; Yang, W.-P.; Zhu, J.; Madireddi, M. T.; Lawrence, R. M.; Wong, T. W.; Rupnow, B. A. Cancer cell dependence on unsaturated fatty acids implicates stearoyl-CoA desaturase as a target for cancer therapy Mol. Cancer Res. 2011, 9, 1551-1561
146. Hess, D.; Chisholm, J. W.; Igal, R. A. Inhibition of stearoylCoA desaturase activity blocks cell cycle progression and induces programmed cell death in lung cancer cells PLoS One 2010, 5, e11394
147. Zhang, H.; Li, H.; Ho, N.; Li, D.; Li, S. SCD1 plays a tumor-suppressive role in survival of leukemia stem cells and the development of chronic myeloid leukemia Mol. Cell. Biol. 2012, 32, 1776-1787
148. Morgan-Lappe, S. E.; Tucker, L. A.; Huang, X.; Zhang, Q.; Sarthy, A. V.; Zakula, D.; Vernetti, L.; Schurdak, M.; Wang, J.; Fesik, S. W. Identification of Ras-related nuclear protein, targeting protein for Xenopus kinesin-like protein 2, and stearoyl-CoA desaturase 1 as promising cancer targets from an RNAi-based screen Cancer Res. 2007, 67, 4390-4398
149. Kim, S.-J.; Choi, H.; Park, S.-S.; Chang, C.; Kim, E. Stearoyl CoA desaturase (SCD) facilitates proliferation of prostate cancer cells through enhancement of androgen receptor transactivation Mol. Cell 2011, 31, 371-377
150. Du, X.; Wang, Q.-R.; Chan, E.; Merchant, M.; Liu, J.; French, D.; Ashkenazi, A.; Qing, J. FGFR3 Stimulates Stearoyl CoA Desaturase 1 Activity to Promote Bladder Tumor Growth Cancer Res. 2012, 72, 5843-5855
151. Scaglia, N.; Igal, R. A. Stearoyl-CoA desaturase is involved in the control of proliferation, anchorage-independent growth, and survival in human transformed cells J. Biol. Chem. 2005, 280, 25339-25349