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Gw0742 CAS 317318-84-6 SARM steroids white powder raw material
1. Name: GW-0742
2. Other Name: GW610742
3. CAS: 317318-84-6
4. Molecular Formula:C21H17F4NO3S2
5. Formula Weight:471.5
6. appearance:white solid
7. Mp:134.5-135.5 °C
Gw0742 Description:
1. GW0742 is a high affinity PPAR-β/δ agonist reduces lung inflammation induced by bleomycin instillation in mice.
2. A high throughput screening campaign was conducted to identify small molecules with the ability to inhibit
3. the interaction between the vitamin D receptor (VDR) and steroid receptor coactivator.
4. These inhibitors represent novel molecular probes to modulate gene regulation mediated by VDR. The peroxisome proliferator-activated receptor δ (PPARδ) agonist GW0742 was among the identified VDR-coactivator inhibitors and has been characterized herein as a pan nuclear receptor antagonist at concentrations higher than 12.1 µM.
5. The highest antagonist activity for GW0742 was found for VDR and the androgen receptor (AR). Surprisingly, GW0742 behaved as PPAR agonist/antagonist activating transcription at lower concentration and inhibiting this effect at higher concentrations.
6. A unique spectroscopic property of GW0742 was identified as well. In the presence of rhodamine-derived molecules, GW0742+ increased fluorescence intensity and fluorescence polarization at an excitation wavelength of 595 nm and emission wavelength of 615 nm in a dose dependent manner.
7. The GW0742-inhibited NR-coactivator binding resulted in a reduced expression of five different NR target genes in LNCaP cells in the presence of agonist. Especially VDR target genes CYP24A1, IGFBP-3 and TRPV6 were negatively regulated by GW0742.
8. GW0742 is the first VDR ligand inhibitor lacking the secosteroid structure of VDR ligand antagonists. Nevertheless, the VDR-meditated downstream process of cell differentiation was antagonized by GW0742 in HL-60 cells that were pretreated with the endogenous VDR agonist 1,25-dihydroxyvitamin D3.
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