Dutasteride-¹³C,¹⁵N,d  (Synonyms: GG 745-¹³C,¹⁵N,d; GI 198745-¹³C,¹⁵N,d)

Dutasteride-¹³C,¹⁵N,d is ¹⁵N and deuterated labeled Dutasteride (HY-13613). Dutasteride (GG745) is a potent inhibitor of both 5α-reductase isozymes. Dutasteride may possess off-target effects on the androgen receptor (AR) due to its structural similarity to DHT^[1].

Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs^[1].
Dutasteride inhibits ³H-T conversion to ³H-DHT and, as anticipated, inhibits T-induced secretion of PSA and proliferation. However the drug also inhibited DHT-induced PSA secretion and cell proliferation (IC₅₀ approximately 1 μM)^[2].
Dutasteride competes for binding the LNCaP cell AR with an IC₅₀ approximately 1.5 μM. High concentrations of dutasteride (10-50 μM), but not finasteride, in steroid-free medium, resulted in enhanced cell death, possibly by apoptosis^[2].
Dutasteride reduces cell viability and cell proliferation in both cell lines tested (androgen-responsive (LNCaP) and androgen-unresponsive (DU145) human prostate cancer (PCa)) ^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

GG745 has a terminal half-life of approximately 240 hr, and single doses of >10 mg decreased DHT levels significantly more than did single 5-mg doses of finasteride^[4].
In placebo treated men without prostate cancer there was an 8.3% median increase in PSA at month 24 compared with -59.5% in those who received dutasteride, using doubled values to correct for dutasteride treatment^[5].
Toxicity: Dutasteride may affect male fertility and steroid hormone dynamics. Therefore, a 21-day reproduction study was conducted to determine the effects of dutasteride (10, 32 and 100 μg/L) on fish reproduction. Exposure to dutasteride significantly reduced fecundity of fish and affected several aspects of reproductive endocrine functions in both males and females^[6].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

531.52

C₂₆¹³CH₂₉DF₆N¹⁵NO₂

O=[13C]([C@H]1C([2H])C[C@]2([H])[C@]1(C)CC[C@]3([H])[C@@]4(C)C=CC([15NH][C@]4([H])CC[C@]32[H])=O)NC5=CC(C(F)(F)F)=CC=C5C(F)(F)F

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019 Feb;53(2):211-216.  [Content Brief]

  [2]. Lazier CB, et al. Dutasteride, the dual 5alpha-reductase inhibitor, inhibits androgen action and promotes cell death in the LNCaP prostate cancer cell line. Prostate. 2004 Feb 1;58(2):130-44.  [Content Brief]

  [3]. Biancolella M, et al. Effects of dutasteride on the expression of genes related to androgen metabolism and related pathway in human prostate cancer cell lines. Invest New Drugs. 2007 Oct;25(5):491-7.  [Content Brief]

  [4]. Bramson HN, et al. Unique preclinical characteristics of GG745, a potent dual inhibitor of 5AR. J Pharmacol Exp Ther. 1997 Sep;282(3):1496-502.  [Content Brief]

  [5]. Andriole GL, et al. Clinical usefulness of serum prostate specific antigen for the detection of prostate cancer is preserved in men receiving the dual 5alpha-reductase inhibitor dutasteride. J Urol. 2006 May;175(5):1657-62.  [Content Brief]

  [6]. Margiotta-Casaluci L, et al. Mode of action of human pharmaceuticals in fish: the effects of the 5-alpha-reductase inhibitor, dutasteride, on reproduction as a case study. Aquat Toxicol. 2013 Mar 15;128-129:113-23.  [Content Brief]