Pharmacodynamics and subchronic toxicity in mice and monkeys of ISIS 388626, a second-generation antisense oligonucleotide that targets human sodium glucose cotransporter 2

Journal of Pharmacology and Experimental Therapeutics

Volumn 343, Issue 2, 2012, Pages 489-496

  Zanardi, Thomas A ^a   Han, Su Cheol ^b   Jeong, Eun Ju ^b   Rime, Soyub ^b   Yu, Rosie Z ^a   Chakravarty, Kaushik ^a   Henry, Scott P ^a  

^a ISIS PHARMACEUTICALS   (United States)

^b Korea Institute of Toxicology   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE; ISIS 388626; MESSENGER RNA; SODIUM GLUCOSE COTRANSPORTER 2; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; BASOPHIL; CHRONIC TOXICITY; CONTROLLED STUDY; DOSE RESPONSE; DRUG ABSORPTION; DRUG DISTRIBUTION; DRUG ELIMINATION; DRUG HALF LIFE; DRUG MEGADOSE; DRUG TARGETING; FEMALE; GLUCOSURIA; HAPLORHINI; HYPOGLYCEMIA; KIDNEY DYSFUNCTION; KIDNEY TUBULE CELL; MALE; MAXIMUM PLASMA CONCENTRATION; MOUSE; NONHUMAN; PLASMA CONCENTRATION-TIME CURVE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN SYNTHESIS INHIBITION; TIME TO MAXIMUM PLASMA CONCENTRATION; WEIGHT GAIN;

ANIMALS; AREA UNDER CURVE; CHEMISTRY, PHARMACEUTICAL; DOSE-RESPONSE RELATIONSHIP, DRUG; ELECTROCARDIOGRAPHY; FEMALE; HALF-LIFE; HEMODYNAMICS; INJECTIONS, SUBCUTANEOUS; KIDNEY; MACACA FASCICULARIS; MALE; MICE; MICE, INBRED ICR; OLIGODEOXYRIBONUCLEOTIDES; OLIGONUCLEOTIDES, ANTISENSE; PHARMACOKINETICS; RNA, MESSENGER; SODIUM-GLUCOSE TRANSPORTER 2;

EID: 84867619259     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.112.197426     Document Type: Article

References (21)

1. Bailey CJ (2011) Renal glucose reabsorption inhibitors to treat diabetes. Trends Pharmacol Sci 32:63-71.
2. Beaucage SL and Iyer RP (1992) Advances in the synthesis of oligonucleotides by the phosphoramidite approach. Tetrahedron 48:2223-2311.
3. Bustin SA (2000) Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays. J Mol Endocrinol 25:169-193.
4. Fujimori Y, Katsuno K, Nakashima I, Ishikawa-Takemura Y, Fujikura H, and Isaji M (2008) Remogliflozin etabonate, in a novel category of selective low-affinity sodium glucose cotransporter (SGLT2) inhibitors, exhibits antidiabetic efficacy in rodent models. J Pharmacol Exp Ther 327:268-276.
5. Han S, Hagan DL, Taylor JR, Xin L, Meng W, Biller SA, Wetterau JR, Washburn WN, and Whaley JM (2008) Dapagliflozin, a selective SGLT2 inhibitor, improves glucose homeostasis in normal and diabetic rats. Diabetes 57:1723-1729.
6. Henry SP, Bolte H, Auletta C, and Kornbrust DJ (1997a) Evaluation of the toxicity of ISIS 2302, a phosphorothioate oligonucleotide, in a four-week study in cynomolgus monkeys. Toxicology 120:145-155.
7. Henry SP, Geary RS, Yu R, and Levin AA (2001) Drug properties of second-generation antisense oligonucleotides: how do they measure up to their predecessors? Curr Opin Investig Drugs 2:1444-1449.
8. Henry SP, Giclas PC, Leeds J, Pangburn M, Auletta C, Levin AA, and Kornbrust DJ (1997b) Activation of the alternative pathway of complement by a phosphorothioate oligonucleotide: potential mechanism of action. J Pharmacol Exp Ther 281:810-816.
9. Henry SP, Johnson M, Zanardi TA, Fey R, Auyeung D, Lappin PB, and Levin AA (2012) Renal uptake and tolerability of a 2′-O-methoxyethyl modified antisense oligonucleotide (ISIS 113715) in monkey. Toxicology 301:13-20.
10. Henry SP, Kim TW, Kramer-Stickland K, Zanardi TA, Fey RA, and Levin AA (2008) Toxicologic properties of 2′-o-methoxyethyl chimeric antisense inhibitors in animals and man, in Antisense Drug Technology: Principles, Strategies, and Applications, 2nd ed (Crooke ST ed) pp 327-364, CRC Press/Taylor & Francis Group, Boca Raton, FL.
11. +/glucose cotransporter SGLT2. Delineation of the major renal reabsorptive mechanism for D-glucose. J Clin Invest 93:397-404.
12. Monteith DK, Horner MJ, Gillett NA, Butler M, Geary R, Burckin T, Ushiro-Watanabe T, and Levin AA (1999) Evaluation of the renal effects of an antisense phosphorothioate oligodeoxynucleotide in monkeys. Toxicol Pathol 27:307-317.
13. Murphy AT, Brown-Augsburger P, Yu RZ, Geary RS, Thibodeaux S, and Ackermann BL (2005) Development of an ion-pair reverse-phase liquid chromatographic/tandem mass spectrometry method for the determination of an 18-mer phosphorothioate oligonucleotide in mouse liver tissue. Eur J Mass Spectrom (Chicester, Eng) 11:209-215.
14. Nolan T, Hands RE, and Bustin SA (2006) Quantification of mRNA using real-time RT-PCR. Nat Protoc 1:1559-1582.
15. Sheehan JP and Phan TM (2001) Phosphorothioate oligonucleotides inhibit the intrinsic tenase complex by an allosteric mechanism. Biochemistry 40:4980-4989.
16. VanGuilder HD, Vrana KE, and Freeman WM (2008) Twenty-five years of quantitative PCR for gene expression analysis. Biotechniques 44:619-626.
17. Wancewicz EV, Siwkowski A, Meibohm B, Yates CR, Pearce M, Matson J, Booten S, Murray SF, Hung G, Geary RS, et al. (2008) Long-term safety and efficacy of ISIS 388626, an optimized SGLT2 antisense inhibitor, in multiple diabetic and euglycemic species, at the American Diabetes Association 68th Scientific Sessions; 2008 June 6-10; San Francisco, CA. Abstract 334-OR. American Diabetes Association, Alexandria, VA.
18. Wood IS and Trayhurn P (2003) Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins. Br J Nutr 89:3-9.
19. Yu RZ, Baker B, Chappell A, Geary RS, Cheung E, and Levin AA (2002) Development of an ultrasensitive noncompetitive hybridization-ligation enzyme-linked immunosorbent assay for the determination of phosphorothioate oligodeoxynucleotide in plasma. Anal Biochem 304:19-25.
20. Yu RZ, Geary RS, Zanardi TA, Norris DA, Bhanot S, and Grundy JS (2009) Cross-species pharmacokinetic (PK) comparison of a 12-mer 2′-methoxyethyl (MOE) antisense oligonucleotide, ISIS 388626, targeting sodium glucose cotransporter 2 (SGLT2), at the Annual Meeting of the American Association of Pharmaceutical Scientists; 2009 Nov 8-12; Los Angeles, CA. Abstract R6042. American Association of Pharmaceutical Scientists, Arlington, VA.
21. Yu RZ, Kim TW, Hong A, Watanabe TA, Gaus HJ, and Geary RS (2007) Cross-species pharmacokinetic comparison from mouse to man of a second-generation antisense oligonucleotide, ISIS 301012, targeting human apolipoprotein B-100. Drug Metab Dispos 35:460-468.