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• W2170332110 endingPage "670" @default.
• W2170332110 startingPage "663" @default.
• W2170332110 abstract "Selective androgen receptor modulators (SARMs) are a new class of molecules in development to treat a variety of diseases. SARMs maintain the beneficial effects of androgens, including increased muscle mass and bone density, while having reduced activity on unwanted side effects. The mechanisms responsible for the tissue-selective activity of SARMs are not fully understood, and the pharmacokinetic (PK)/pharmacodynamic (PD) relationships are poorly described. Tissue-specific compound distribution potentially could be a mechanism responsible for apparent tissue selectivity. We examined the PK/PD relationship of a novel SARM, LGD-3303 [9-chloro-2-ethyl-1-methyl-3-(2,2,2-trifluoroethyl)-3<i>H</i>-pyrrolo[3,2-<i>f</i>]quinolin-7(6<i>H</i>)-one], in a castrated rat model of androgen deficiency. LGD-3303 has potent activity on levator ani muscle but is a partial agonist on the preputial gland and ventral prostate. LGD-3303 never stimulated ventral prostate above intact levels despite increasing plasma concentrations of compound. Tissue-selective activity was maintained when LGD-3303 was dosed orally or by continuous infusion, two routes of administration with markedly different time versus exposure profiles. Despite the greater muscle activity relative to prostate activity, local tissue concentrations of LGD-3303 were higher in the prostate than in the levator ani muscle. LGD-3303 has SARM properties that are independent of its pharmacokinetic profile, suggesting that the principle mechanism for tissue-selective activity is the result of altered molecular interactions at the level of the androgen receptor." @default.
• W2170332110 created "2016-06-24" @default.
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• W2170332110 date "2008-11-18" @default.
• W2170332110 modified "2023-10-03" @default.
• W2170332110 title "Pharmacokinetics and Pharmacodynamics of LGD-3303 [9-Chloro-2-ethyl-1-methyl-3-(2,2,2-trifluoroethyl)-3<i>H</i>-pyrrolo-[3,2-<i>f</i>]quinolin-7(6<i>H</i>)-one], an Orally Available Nonsteroidal-Selective Androgen Receptor Modulator" @default.
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• W2170332110 doi "https://doi.org/10.1124/jpet.108.146811" @default.
• W2170332110 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19017848" @default.
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