Nonsteroidal progesterone receptor ligands. 2. High-affinity ligands with selectivity for bone cell progesterone receptors.

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Combs DW, Reese K, Cornelius LA, Gunnet JW, Cryan EV, Granger KS, Jordan JJ, Demarest KT

Nonsteroidal progesterone receptor ligands. 2. High-affinity ligands with selectivity for bone cell progesterone receptors.

J Med Chem. 1995 Dec 8;38(25):4880-4.

PubMed ID

8523400 [ View in PubMed

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Abstract

A novel series of nonsteroidal heterocycles was discovered which display cell-type selective, high-affinity (nanomolar) binding to the progesterone receptors from TE85 osteosarcoma cells but > 1 microM binding affinity to the progesterone receptors from T47D and ZR75 human breast carcinoma cells. Structure-activity relationships were developed for a set of these compounds, and a representative analog 1-(3,4-dichlorobenzoyl)-3-phenyl-1,4,5,6-tetrahydropyridazine++ + (1i, RWJ 25333) was chosen for further evaluation. RWJ 25333 stimulated the in vitro proliferation of human osteoblast-like cells but not human breast cells.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Norethisterone	Progesterone receptor	IC 50 (nM)	3.2	N/A	N/A	Details
Progesterone	Progesterone receptor	IC 50 (nM)	17	N/A	N/A	Details