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ODM-201 Darolutamide BAY-1841788 1297538-32-9
ODM-201 is a new-generation inhibitor of androgen receptor with Ki value of 11 nM [1].
Androgen receptor is a type of nuclear receptor that is activated by androgen and functions as a DNA-binding transcription factor that regulates gene expression. Activation of androgen receptor (AR) is crucial for prostate cancer growth [1].
ODM-201 is a high-affinity and potent androgen receptor antagonist. In competitive AR binding assays, ODM-201 exhibited Ki value of 11 nM. In AR-HEK293 cells stably expressing full-length human AR (hAR) and an androgen-responsive luciferase reporter gene construct, ODM-201 and its major metabolite ORM-15341 inhibited AR-mediated transactivation with IC50 values of 26 nM and 38 nM. In human U2-OS osteosarcoma cells expressing wtAR or mutant AR(F876L), AR(W741L), or AR(T877A), ODM-201 and ORM-15341 also functioned as full antagonists. in AR overexpressing HS-HEK293 cells, ODM-201 inhibited the androgen-induced nuclear translocation of overexpressed AR. In the VCaP cell line with endogenous AR gene amplification and AR overexpression, ODM-201 inhibited androgen-induced cell proliferation with IC50 value of 230 nM.
In castrated male nude mice with subcutaneously injected VCaP cells, orally treatment with ODM-201 (50 mg/kg) once (qd) or twice daily (bid) for 37 days, ODM-201 showed a significant antitumor activity with both doses. There was no sign of treatment-related toxicities. In orthotopic VCaP tumor-bearing intact nude mice, ODM-201 (50 mg/kg, bid) significantly inhibited tumor growth but did not affect the testosterone levels in serum. ODM-201 couldn’t penetrate the blood-brain barrier [1].
| Cas No. | 1297538-32-9 | ||
| Synonyms | BAY 1841788 | ||
| Chemical Name | N-((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(1-hydroxyethyl)-1H-pyrazole-3-carboxamide | ||
| Canonical SMILES | N#CC1=C(Cl)C=C(C2=NN(C[C@H](C)NC(C3=NNC(C(O)C)=C3)=O)C=C2)C=C1 | ||
| Formula | C19H19ClN6O2 | M.Wt | 398.85 |
| Solubility | ≥ 19.95mg/mL in DMSO | Storage | Store at -20°C |
Reference:
Moilanen AM, Riikonen R, Oksala R, et al. Discovery of ODM-201, a new-generation androgen receptor inhibitor targeting resistance mechanisms to androgen signaling-directed prostate cancer therapies. Sci Rep, 2015, 5: 12007.
For Research Use Only. Not Intended for Diagnostic or Therapeutic Use.