11-(pyridinylphenyl)steroids--a new class of mixed-profile progesterone agonists/antagonists

Jos Rewinkel, Rewinkel J, Mark Enthoven, Enthoven M, Irene Golstein, Golstein I, Marcel van der Rijst, van der Rijst M, André Scholten, Scholten A, van Tilborg M, Martin van Tilborg, de Weys D, Dirk de Weys, Jeffry Wisse, Wisse J, Hamersma H, Hans Hamersma
Bioorganic & medicinal chemistry · 2008 · doi:10.1016/j.bmc.2008.01.010 · PMID:18243712
other OA: green public-domain-us
🔓 Open OA copy Full text JSON View on PubMed View at publisher
⚙ AI-generated summary by gemini-2.5-flash-lite, 2026-07-16 ⓘ

Researchers identified a new class of 11beta-[4-(heteroaryl)phenyl]-substituted pregnanes that exhibit a balanced mixed progesterone receptor agonist/antagonist activity, unlike existing SPRMs.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

⚙ AI-generated deep summary by claude@2026-07, 2026-07-16 · read from full text ⓘ

This paper reports pharmacological testing of a new class of 11-(pyridinylphenyl)steroid compounds as mixed-profile progesterone receptor (PRB) agonists/antagonists. Using human PRB expressed in CHO cells, the authors measured agonist activity as EC50 values and antagonist activity as IC50 values based on inhibition of Org 2058–induced transactivation; the reported EC50 and IC50 values span from subnanomolar levels (e.g., ~0.12–0.49 nM) to high values where agonist activity is not observed up to >100 nM. A major limitation explicitly reflected in the presented text is that activity characterization is confined to PRB function in CHO-cell transactivation assays without additional in vivo, tissue, or mechanism details. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Abstract

Recently, a new class (often referred to as SPRMs: selective progesterone receptor modulators) of progesterone receptor ligands with mixed agonist/antagonist properties has been described. Such compounds are envisaged, for example, as treatment for endometriosis, uterine fibroids, and leiomyomas. Existing SPRMs include Asoprisnil 1 and Uliprisnil acetate 2. In our hands, however, these compounds proved to have a predominantly or exclusively antagonistic in vitro profile, which may make this type of compound less attractive, for example, as contraceptives. We therefore aimed at a class of mixed-profile compounds that would show a more evenly balanced agonist/antagonist profile. A novel class of 11beta-[4-(heteroaryl)phenyl]-substituted pregnanes was identified that displayed the desired balance. Contrary to known SPRMs, this novel class of MPP (mixed-profile progestagen) was found to have a truly mixed activity, including a sizeable agonist component.
Full text 7,416 characters · extracted from oa-html · click to expand
Report error Found 44 Enz. Inhib. hit(s) with all data for entry = 50038369 Affinity DataEC50: 0.120nMAssay Description:Agonist activity at human PRB expressed in CHO cellsMore data for this Ligand-Target Pair Affinity DataIC50: 0.130nMAssay Description:Antagonist activity at human PRB expressed in CHO cells assessed as inhibition of Org 2058 induced-transactivationMore data for this Ligand-Target Pair Affinity DataEC50: 0.150nMAssay Description:Agonist activity at human PRB expressed in CHO cellsMore data for this Ligand-Target Pair Affinity DataIC50: 0.200nMAssay Description:Antagonist activity at human PRB expressed in CHO cells assessed as inhibition of Org 2058 induced-transactivation relative to Org 31710More data for this Ligand-Target Pair Affinity DataIC50: 0.200nMAssay Description:Antagonist activity at human PRB expressed in CHO cells assessed as inhibition of Org 2058 induced-transactivationMore data for this Ligand-Target Pair Affinity DataEC50: 0.200nMAssay Description:Agonist activity at human PRB expressed in CHO cellsMore data for this Ligand-Target Pair Affinity DataIC50: 0.200nMAssay Description:Antagonist activity at human PRB expressed in CHO cells assessed as inhibition of Org 2058 induced-transactivation relative to Org 31710More data for this Ligand-Target Pair Affinity DataIC50: 0.200nMAssay Description:Antagonist activity at human PRB expressed in CHO cells assessed as inhibition of Org 2058 induced-transactivationMore data for this Ligand-Target Pair Affinity DataEC50: 0.230nMAssay Description:Agonist activity at human PRB expressed in CHO cellsMore data for this Ligand-Target Pair Affinity DataIC50: 0.270nMAssay Description:Antagonist activity at human PRB expressed in CHO cells assessed as inhibition of Org 2058 induced-transactivationMore data for this Ligand-Target Pair Affinity DataEC50: 0.290nMAssay Description:Agonist activity at human PRB expressed in CHO cellsMore data for this Ligand-Target Pair Affinity DataIC50: 0.330nMAssay Description:Antagonist activity at human PRB expressed in CHO cells assessed as inhibition of Org 2058 induced-transactivationMore data for this Ligand-Target Pair Affinity DataEC50: 0.360nMAssay Description:Agonist activity at human PRB expressed in CHO cellsMore data for this Ligand-Target Pair Affinity DataIC50: 0.430nMAssay Description:Antagonist activity at human PRB expressed in CHO cells assessed as inhibition of Org 2058 induced-transactivationMore data for this Ligand-Target Pair Affinity DataIC50: 0.470nMAssay Description:Antagonist activity at human PRB expressed in CHO cells assessed as inhibition of Org 2058 induced-transactivationMore data for this Ligand-Target Pair Affinity DataEC50: 0.490nMAssay Description:Agonist activity at human PRB expressed in CHO cellsMore data for this Ligand-Target Pair Affinity DataEC50: 0.490nMAssay Description:Agonist activity at human PRB expressed in CHO cellsMore data for this Ligand-Target Pair Affinity DataEC50: 0.510nMAssay Description:Agonist activity at human PRB expressed in CHO cellsMore data for this Ligand-Target Pair Affinity DataIC50: 0.550nMAssay Description:Antagonist activity at human PRB expressed in CHO cells assessed as inhibition of Org 2058 induced-transactivationMore data for this Ligand-Target Pair Affinity DataIC50: 0.600nMAssay Description:Antagonist activity at human PRB expressed in CHO cells assessed as inhibition of Org 2058 induced-transactivationMore data for this Ligand-Target Pair Affinity DataIC50: 0.610nMAssay Description:Antagonist activity at human PRB expressed in CHO cells assessed as inhibition of Org 2058 induced-transactivationMore data for this Ligand-Target Pair Affinity DataIC50: 0.630nMAssay Description:Antagonist activity at human PRB expressed in CHO cells assessed as inhibition of Org 2058 induced-transactivationMore data for this Ligand-Target Pair Affinity DataEC50: 0.660nMAssay Description:Agonist activity at human PRB expressed in CHO cellsMore data for this Ligand-Target Pair Affinity DataEC50: 0.740nMAssay Description:Agonist activity at human PRB expressed in CHO cellsMore data for this Ligand-Target Pair Affinity DataIC50: 0.75nMAssay Description:Antagonist activity at human PRB expressed in CHO cells assessed as inhibition of Org 2058 induced-transactivationMore data for this Ligand-Target Pair Affinity DataEC50: 0.820nMAssay Description:Agonist activity at human PRB expressed in CHO cellsMore data for this Ligand-Target Pair Affinity DataIC50: 0.980nMAssay Description:Antagonist activity at human PRB expressed in CHO cells assessed as inhibition of Org 2058 induced-transactivationMore data for this Ligand-Target Pair Affinity DataEC50: 1nMAssay Description:Agonist activity at human PRB expressed in CHO cellsMore data for this Ligand-Target Pair Affinity DataEC50: 1.10nMAssay Description:Agonist activity at human PRB expressed in CHO cellsMore data for this Ligand-Target Pair Affinity DataEC50: 1.13nMAssay Description:Agonist activity at human PRB expressed in CHO cellsMore data for this Ligand-Target Pair Affinity DataEC50: 1.30nMAssay Description:Agonist activity at human PRB expressed in CHO cellsMore data for this Ligand-Target Pair Affinity DataIC50: 1.30nMAssay Description:Antagonist activity at human PRB expressed in CHO cells assessed as inhibition of Org 2058 induced-transactivationMore data for this Ligand-Target Pair Affinity DataIC50: 2.5nMAssay Description:Antagonist activity at human PRB expressed in CHO cells assessed as inhibition of Org 2058 induced-transactivationMore data for this Ligand-Target Pair Affinity DataEC50: 2.54nMAssay Description:Agonist activity at human PRB expressed in CHO cellsMore data for this Ligand-Target Pair Affinity DataEC50: 2.60nMAssay Description:Agonist activity at human PRB expressed in CHO cellsMore data for this Ligand-Target Pair Affinity DataIC50: 3.14nMAssay Description:Antagonist activity at human PRB expressed in CHO cells assessed as inhibition of Org 2058 induced-transactivationMore data for this Ligand-Target Pair Affinity DataIC50: 3.25nMAssay Description:Antagonist activity at human PRB expressed in CHO cells assessed as inhibition of Org 2058 induced-transactivationMore data for this Ligand-Target Pair Affinity DataIC50: 3.64nMAssay Description:Antagonist activity at human PRB expressed in CHO cells assessed as inhibition of Org 2058 induced-transactivationMore data for this Ligand-Target Pair Affinity DataEC50: 4nMAssay Description:Agonist activity at human PRB expressed in CHO cellsMore data for this Ligand-Target Pair Affinity DataIC50: 7.89nMAssay Description:Antagonist activity at human PRB expressed in CHO cells assessed as inhibition of Org 2058 induced-transactivationMore data for this Ligand-Target Pair Affinity DataIC50: 8.48nMAssay Description:Antagonist activity at human PRB expressed in CHO cells assessed as inhibition of Org 2058 induced-transactivationMore data for this Ligand-Target Pair Affinity DataIC50: 14.8nMAssay Description:Antagonist activity at human PRB expressed in CHO cells assessed as inhibition of Org 2058 induced-transactivationMore data for this Ligand-Target Pair Affinity DataEC50: >100nMAssay Description:Agonist activity at human PRB expressed in CHO cellsMore data for this Ligand-Target Pair Affinity DataEC50: >100nMAssay Description:Agonist activity at human PRB expressed in CHO cellsMore data for this Ligand-Target Pair

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

⚙ Ask this paper AI returns verbatim quotes from the full text · source: oa-html ⓘ

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Condition tags

endometriosis

MeSH descriptors

Progesterone Steroids Ligands Pregnanes Pregnanes Progesterone Progesterone Progesterone Receptors, Progesterone Steroids Structure-Activity Relationship

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. The paper's references may be in our DB but unresolved to ``paper_id`` (resolution happens at ingest when the cited DOI matches a row we already have). Run the cross-source citation reconcile pass to retry.

Source provenance

europepmc
last seen: 2026-08-28T06:11:01.063540+00:00
pubmed
last seen: 2026-05-13T22:14:42.556217+00:00
unpaywall
last seen: 2026-05-14T19:30:52.867331+00:00
License: public-domain-us · commercial use OK · attribution required
Courtesy of the U.S. National Library of Medicine