E2 deficiency in elderly people has directly an effect on the skeleton and can lead to osteoporosis. As 17##-hydroxysteroid dehydrogenase type 2 (17##-HSD2) catalyses the conversion between active 17##-hydroxysteroid estradiol (E2) and testosterone (T) into their less active 17-ketosteroid and has been found in bones, 17##-HSD2 inhibitor may provide a new approach in the onset of osteoporosis. more ..
Target
Tested Compounds:
Description:
Title: Discovery of a new class of bicyclic substituted hydroxyphenylmethanones as 17##-hydroxysteroid dehydrogenase type 2 (17##-HSD2) inhibitors for the treatment of osteoporosis.
Abstract: E2 deficiency in elderly people has directly an effect on the skeleton and can lead to osteoporosis. As 17##-hydroxysteroid dehydrogenase type 2 (17##-HSD2) catalyses the conversion between active 17##-hydroxysteroid estradiol (E2) and testosterone (T) into their less active 17-ketosteroid and has been found in bones, 17##-HSD2 inhibitor may provide a new approach in the onset of osteoporosis. Bicyclic substituted hydroxyphenylmethanone derivatives were synthesised as steroidomimetics of the substrate E2 and were evaluated for their 17##-HSD2 inhibition and their selectivity toward 17##-HSD1, catalysing the reverse reaction the conversion of estrone (E1) into E2. Highly selective compounds (11, 12, 14, 21 and 22) have been identified, the most promising one (12) showing an IC(50) value in the low nanomolar range (101##nM) and a selectivity factor of 13 toward 17##-HSD1. These results make compound 12 an interesting candidate for further biological evaluation.
(PMID: 21945251)
Abstract: E2 deficiency in elderly people has directly an effect on the skeleton and can lead to osteoporosis. As 17##-hydroxysteroid dehydrogenase type 2 (17##-HSD2) catalyses the conversion between active 17##-hydroxysteroid estradiol (E2) and testosterone (T) into their less active 17-ketosteroid and has been found in bones, 17##-HSD2 inhibitor may provide a new approach in the onset of osteoporosis. Bicyclic substituted hydroxyphenylmethanone derivatives were synthesised as steroidomimetics of the substrate E2 and were evaluated for their 17##-HSD2 inhibition and their selectivity toward 17##-HSD1, catalysing the reverse reaction the conversion of estrone (E1) into E2. Highly selective compounds (11, 12, 14, 21 and 22) have been identified, the most promising one (12) showing an IC(50) value in the low nanomolar range (101##nM) and a selectivity factor of 13 toward 17##-HSD1. These results make compound 12 an interesting candidate for further biological evaluation.
(PMID: 21945251)
Categorized Comment
ChEMBL Assay Type: Binding
ChEMBL Assay Data Source: Scientific Literature
ChEMBL Target ID: 19
ChEMBL target type: Target is a single protein chain
ChEMBL Assay Data Source: Scientific Literature
ChEMBL Target ID: 19
ChEMBL target type: Target is a single protein chain
Result Definitions
| TID | Name | Description | Histogram | Type | Unit | |
|---|---|---|---|---|---|---|
| Outcome | The BioAssay activity outcome | Outcome | ||||
| 1 | RBA activity comment | RBA activity comment | String | |||
| 2 | RBA standard flag | RBA standard flag |  | Integer | ||
| 3 | RBA qualifier | RBA qualifier | String | |||
| 4 | RBA published value | RBA published value | | Float | % | |
| 5 | RBA standard value | RBA standard value | | Float | % |
Data Table (Concise)
Classification
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