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ODM-201

Names

[ CAS No. ]:
1297538-32-9

[ Name ]:
ODM-201

[Synonym ]:
UNII:X05U0N2RCO
ODM-201
1H-Pyrazole-3-carboxamide, N-[(1S)-2-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]-1-methylethyl]-5-(1-hydroxyethyl)-
N-{(2S)-1-[3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl]-2-propanyl}-5-(1-hydroxyethyl)-1H-pyrazole-3-carboxamide
BAY-1841788
Darolutamide

Biological Activity

[Description]:

ODM-201 is a potent androgen receptor (AR) antagonist with an IC50 of 26 nM in AR-HEK293 cells.

[Related Catalog]:

Signaling Pathways >> Others >> Androgen Receptor
Research Areas >> Cancer

[Target]

IC50: 26 nM (AR-HEK293 cells, AR)[1]


[In Vitro]

In competitive AR binding assays, the inhibition constant (Ki) values of ODM-201 are 11 nM. ODM-201and ORM-15341 suppresse androgen-induced cell proliferation more efficaciously than enzalutamide or ARN-509, IC50 values being 230 and 170 nM for ODM-201 and ORM-15341 vs. 410 and 420 nM for enzalutamide and ARN-509. ODM-201 has no effect on the viability of AR-negative cell lines tested, DU-145 prostate cancer cells and H1581 lung cancer cells confirming that the antiproliferative properties of ODM-201 and ORM-15341 are specific to AR-dependent PC cells[1].

[In Vivo]

ODM-201 showes a significant antitumor activity with both doses, 50 mg/kg twice daily being more efficacious compared to castrated, untreated mice (p < 0.001) or enzalutamide (p = 0.0245), which also showes inhibition of tumor growth (p < 0.05) vs. castrated, untreated mice. Further, there is no sign of treatment-related toxicities; the body weights of mice treated with ODM-201 twice daily do not decrease significantly during the treatment[1].

[Cell Assay]

To study the antiproliferative properties of ODM-201 and ORM-15341, the VCaP cell line originally derived from a bone metastasis of a CRPC patient is used. The VCaP cell line is characterized with endogenous AR gene amplification and AR overexpression30, typical for CRPC. VCaP cells are cultured in RPMI-1640 medium and supplemented with 10% fetal bovine serum (FBS), 100 UI/mL penicillin, 100 μ g/mL streptomycin, and 4 mM VCaP[1].

[Animal admin]

To elucidate the in vivo efficacy of ODM-201 in a CRPC mouse model, castrated male nude mice with subcutaneously injected VCaP cells are treated orally with ODM-201 (50 mg/kg) once (qd) or twice daily (bid), or with enzalutamide (20 mg/kg, qd) for 37 days. The dose for enzalutamide is selected based on previously published studies9 and our pharmacokinetic (PK) analyses which reveales that in mice the systemic exposure (AUC0–24) for this dose of enzalutamide is 2.5 times higher than that for ODM-201 (50 mg/kg, bid). Moreover, enzalutamide exhibited a long plasma half-life (18.3 hours) while the half-life of ODM-201 in mice is not optimal (1.6 hours) supporting once daily dosing for enzalutamide and higher dose and more frequent dosing for ODM-201[1].

[References]

[1]. Moilanen AM, et al. Discovery of ODM-201, a new-generation androgen receptor inhibitor targeting resistance mechanisms toandrogen signaling-directed prostate cancer therapies. Sci Rep. 2015 Jul 3;5:12007. doi: 10.1038/srep12007.


[Related Small Molecules]

ARN-509 | Dehydroepiandrosterone | Flutamide | Danazol | 3,3'-Diindolylmethane | AZD3514 | RAD140 | BMS-564929 | GLPG0492 | Cyproterone acetate | LGD-4033 | Lupeol | Andarine | MK-0773 | ORM-15341

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
719.5±60.0 °C at 760 mmHg

[ Molecular Formula ]:
C19H19ClN6O2

[ Molecular Weight ]:
398.846

[ Flash Point ]:
388.9±32.9 °C

[ Exact Mass ]:
398.125793

[ LogP ]:
-0.04

[ Vapour Pressure ]:
0.0±2.4 mmHg at 25°C

[ Index of Refraction ]:
1.681

[ Storage condition ]:
-20℃

Related Compounds