ORIC-101

• CAT Number: I019344
• CAS Number: 2222344-98-9
• Molecular Formula: C34H47NO2
• Molecular Weight: 501.74
• Purity: ≥95%
• Synonyms: (8R,9S,10R,11S,13S,14S,17S)-17-(3,3-dimethylbut-1-ynyl)-17-hydroxy-13-methyl-11-[4-[methyl(propan-2-yl)amino]phenyl]-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-one
• InChI: InChI=1S/C34H47NO2/c1-22(2)35(7)25-11-8-23(9-12-25)29-21-33(6)30(16-17-34(33,37)19-18-32(3,4)5)28-14-10-24-20-26(36)13-15-27(24)31(28)29/h8-9,11-12,20,22,27-31,37H,10,13-17,21H2,1-7H3/t27-,28-,29+,30-,31+,33-,34+/m0/s1
• InChIKey: VNLTWJIWEYPBIF-KMSLUKAPSA-N
• SMILES: CC(C)N(C)C1=CC=C(C=C1)C2CC3(C(CCC3(C#CC(C)(C)C)O)C4C2C5CCC(=O)C=C5CC4)C

ORIC-101 is a highly potent and selective glucocorticoid receptor antagonist, with an EC50 of 5.6 nM. Anti-cancer activity. ORIC-101 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
ORIC-101 shows markedly reduced androgen receptor agonism (EC50, 2500 nM) and CYP2C8 and CYP2C9 inhibition profiles (IC50, >10 μM)[1].
ORIC-101 (1-1000 nM) dose-dependently reduces the expression of n GR-mediated target gene (FKBP5 and GILZ), with IC50s of 17.2 and 21.2 nM, respectively[1].
ORIC-101 (75 mg/kg, P.O. twice a day for 16-22 days) enhances the anti-tumor activity in combination with gemcitabine and carboplatin in OVCAR5 xenograft tumor in cortisol-treated mice[1].

Reference

[1]. Rew Y, et al. Discovery of a Potent and Selective Steroidal Glucocorticoid Receptor Antagonist (ORIC-101). J Med Chem. 2018 Sep 13;61(17):7767-7784.
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