Disease relevance of CDB 2914

• The present study was conducted to evaluate the effects of the progesterone receptor modulator CDB-2914 on proliferative activity and apoptosis in cultured human uterine leiomyoma cells [1].

High impact information on CDB 2914

• To identify these pathways, we performed gene expression profiling using ovaries from mice subjected to gonadotropin-induced superovulation in the presence and in the absence of CDB-2914, a synthetic PGR antagonist [2].
• Western blot analysis revealed that treatment with CDB-2914 significantly decreased the expression of PCNA and Bcl-2 protein and increased the expression of cleaved caspase-3 and cleaved PARP in a dose-dependent manner compared with untreated control cultures [1].
• Progesterone receptor modulator CDB-2914 down-regulates proliferative cell nuclear antigen and Bcl-2 protein expression and up-regulates caspase-3 and poly(adenosine 5'-diphosphate-ribose) polymerase expression in cultured human uterine leiomyoma cells [1].
• The novel progesterone receptor antagonists RTI 3021-012 and RTI 3021-022 exhibit complex glucocorticoid receptor antagonist activities: implications for the development of dissociated antiprogestins [3].
• CONCLUSIONS: These results suggest that CDB-2914 down-regulates VEGF, ADM and their receptor contents and modulates PR isoform contents in cultured leiomyoma cells in a cell-type-specific manner [4].

Chemical compound and disease context of CDB 2914

• The concomitant treatment with 10(-6) M CDB-2914 significantly decreased the progesterone-induced VEGF-A, VEGF-B and ADM contents in cultured leiomyoma cells but not in normal myometrial cells [4].

Biological context of CDB 2914

• The AUC(0-168 h) following i.m. injection was 11 226 +/- 1130 ng/ml*h. Therefore, the i.m. bioavailability of CDB-2914 equivalents was 62% [5].
• Luteal phase dose-response relationships of the antiprogestin CDB-2914 in normally cycling women [6].
• The biological effects of CDB-2914 vary according to time of the menstrual cycle that the drug is given [7].
• In the mid-follicular phase, CDB-2914 (50 mg) inhibits follicular development and delays ovulation and menses [7].
• The serum protein binding characteristics of CDB-2914 were also studied [5].

Anatomical context of CDB 2914

• The reduced antiglucocorticoid activity of monodemethylated CDB-2914 and CDB-4124 was confirmed in vivo by the thymus involution assay in adrenalectomized male rats [8].
• The anti-progestin, CDB 2914, had no effect on testis or accessory organ weights, epididymal sperm content or motility, testicular sperm count, spermatogenesis, and fertility of male rats [9].
• Inhibition of Proliferation of Endometrial Stromal Cells by Trichostatin A, RU486, CDB-2914, N-Acetylcysteine, and ICI 182780 [10].

Associations of CDB 2914 with other chemical compounds

• In agreement with our in vivo results, CDB-4124 and CDB-4453, as well as CDB-2914, are potent antiprogestins in vitro, but show considerably less antiglucocorticoid activity than mifepristone [11].
• CONCLUSION: CDB-2914 is at least as effective as levonorgestrel in preventing pregnancies after unprotected intercourse and has a similar side effect profile [12].
• In vitro antiprogestational/antiglucocorticoid activity and progestin and glucocorticoid receptor binding of the putative metabolites and synthetic derivatives of CDB-2914, CDB-4124, and mifepristone [8].

Gene context of CDB 2914

• CDB-2914 treatment alone decreased VEGFR-1, VEGFR-2 and ADMR contents in cultured leiomyoma cells but not in normal myometrial cells [4].
• Compared with untreated control cultures, treatment with CDB-2914 decreased the number of viable cultured leiomyoma cells and the PCNA-positive rate in those cells and increased the TUNEL-positive rate in cultured leiomyoma cells in a dose-dependent manner [1].
• CDB-2914-induced inhibition of uterine weight increase, endometrial glandular arborization and uterine haptoglobin synthesis/secretion correlated with inhibition of pregnancy in mated rabbits [13].
• The endometrial vessels, collagen network, and mRNA levels of VEGF-A were identical during the luteal phase at baseline and in VA-2914 treated women [14].

Analytical, diagnostic and therapeutic context of CDB 2914

• The area under the serum concentration-time curve for 72 h (AUC(0-72)) following i.v. injection was 18 320 +/- 2718 ng/ml*h, and that for oral administration was 10 464 +/- 3248 ng/ml*h. Thus, the oral bioavailability of CDB-2914 equivalents was 56% [5].
• Higher serum equivalents of CDB-2914 were observed by radioimmunoassay than by high performance liquid chromatography detection, indicating a considerable contribution of metabolites [6].

References