In vitro and in vivo evaluation of a 3β-androsterone derivative as inhibitor of 17β-hydroxysteroid dehydrogenase type 3

Structure Confirmation and Evaluation of a Nonsteroidal Inhibitor of 17β-Hydroxysteroid Dehydrogenase Type 10

“…Supplementary Materials: The following are available online at http://www.mdpi.com/2312-7481/4/3/32/s1: (1) Listing of 1 H and 13 C NMR data reported in literature for compound 2; (2) Crystal data and structure refinement for CHUL08 (2); (3) NMR spectra for compound 2 ( 1 H NMR, 13 C NMR (APT), COSY, HSQC, and HMBC).…”

“…Using the HMBC results between the OH and carbons nearby, C-4, C-5, and CH-6 could be assigned to 159.5, 117.5, or 113.0 ppm. Because two of these carbons, C-4 and C-5, are not linked to any protons, a 13 C NMR attached proton test (APT) and HSQC were used to identify CH-6 (117.5 and 7.01 ppm). C-4 and C-5 could not be differentiated between at this point.…”

“…The doublet of CH-15, being in ortho of CH-16, had the highest coupling constant (J = 8.8 Hz) in comparison to CH-18 (J = 3.4 Hz) and could be assigned to the signals at 7.30 and 118.7 ppm. Therefore, CH-18 was positioned at 7.31 ppm (d) in 1 H NMR and at 105.6 ppm in 13 C NMR. Knowing that CH-16 would produce a correlation with C-14 in HMBC but not with C-13, C-14 was consequently assigned to the signal at 145.5 ppm, and, by deduction, C-13 was assigned to the last signal at 131.9 ppm.…”

“…In our efforts to develop inhibitors of the 17β-HSD family, particularly inhibitors of types 1, 2, 3, 5, and 7 for the treatment of estrogen-or androgen-dependent diseases [11][12][13][14][15], we fortuitously identified a first family of steroidal inhibitors of 17β-HSD10 represented by compound 1 [16] (Figure 1). Nonsteroidal inhibitors of this enzyme, although few, have already been reported [17][18][19][20].…”

Investigation of the In Vitro and In Vivo efficiency of RM-532-105, a 17β-hydroxysteroid dehydrogenase type 3 inhibitor, in LAPC-4 prostate cancer cell and tumor models

“…It has shown in vitro 17β-HSD3 inhibitory activity by blocking the transformation of 4-androstene-3,17-dione (4-dione) into T (IC 50 of 5 nM and 13 nM, respectively) in two experiments involving whole HEK-293 cells and LNCaP cells both overexpressing 17β-HSD3 (HEK-293[17β-HSD3] and LNCaP[17β-HSD3], respectively) [ 11 , 14 ]. Moreover, when administered subcutaneously to rats in vivo , RM-532-105 significantly decreased the plasma levels of T and DHT, 2 h after injection [ 15 ].…”