AZD3514

• CAT Number: I000960
• CAS Number: 1240299-33-5
• Molecular Formula: C25H32F3N7O2
• Molecular Weight: 519.56
• Purity: ≥95%
• Synonyms: AZD-3514;AZD 3514
• Target: Androgen Receptor
• Solubility: DMSO 100 mg/ml
• Storage: -20°C
• IC50: 2.2 uM (Ki)
• InChI: InChI=1S/C25H32F3N7O2/c1-18(36)33-14-12-32(13-15-33)16-17-37-21-4-2-19(3-5-21)20-8-10-34(11-9-20)23-7-6-22-29-30-24(25(26,27)28)35(22)31-23/h2-5,20H,6-17H2,1H3
• InChIKey: JMEYDSHPKCSIJC-UHFFFAOYSA-N
• SMILES: CC(N1CCN(CCOC2=CC=C(C3CCN(C4=NN5C(CC4)=NN=C5C(F)(F)F)CC3)C=C2)CC1)=O

AZD3514 is a potent and oral active androgen receptor downregulator with Ki of 2.2 μM and has ability of reducing AR protein expression. AZD3514 binds to the AR ligand binding domain and has selectivity for binding to AR over other nuclear hormone receptors [1]. 


in vitro: AZD3514 inhibits cell growth in prostate cancer cells expressing wild-type (VCaP) and mutated (T877A) AR (LNCaP), but is inactive in AR-negative prostate cancer cells, indicating a dependency on AR for efficacy [2]. 


in vivo: We assessed activity initially in the Hershberger castrated rat assay in which oral dosing of AZD3514 (100mg/kg once-daily for 7 days) significantly inhibited testosterone-induced growth of sexual accessory organs [2]. 


Clinical trial: Open-label Prostate Cancer Study. Phase 1

Reference

1:Continual reassessment method for dose escalation clinical trials in oncology: a comparison of prior skeleton approaches using AZD3514 data. James GD, Symeonides SN, Marshall J, Young J, Clack G.BMC Cancer. 2016 Aug 31;16:703. doi: 10.1186/s12885-016-2702-6. PMID: 27581751 Free PMC Article2:The value of integrating pre-clinical data to predict nausea and vomiting risk in humans as illustrated by AZD3514, a novel androgen receptor modulator. Grant C, Ewart L, Muthas D, Deavall D, Smith SA, Clack G, Newham P.Toxicol Appl Pharmacol. 2016 Apr 1;296:10-8. doi: 10.1016/j.taap.2016.02.007. Epub 2016 Feb 11. PMID: 26876616 3:AZD3514, an oral selective androgen receptor down-regulator in patients with castration-resistant prostate cancer – results of two parallel first-in-human phase I studies. Omlin A, Jones RJ, van der Noll R, Satoh T, Niwakawa M, Smith SA, Graham J, Ong M, Finkelman RD, Schellens JH, Zivi A, Crespo M, Riisnaes R, Nava-Rodrigues D, Malone MD, Dive C, Sloane R, Moore D, Alumkal JJ, Dymond A, Dickinson PA, Ranson M, Clack G, de Bono J, Elliott T.Invest New Drugs. 2015 Jun;33(3):679-90. doi: 10.1007/s10637-015-0235-5. Epub 2015 Apr 30. PMID: 25920479 4:AZD3514: a small molecule that modulates androgen receptor signaling and function in vitro and in vivo. Loddick SA, Ross SJ, Thomason AG, Robinson DM, Walker GE, Dunkley TP, Brave SR, Broadbent N, Stratton NC, Trueman D, Mouchet E, Shaheen FS, Jacobs VN, Cumberbatch M, Wilson J, Jones RD, Bradbury RH, Rabow A, Gaughan L, Womack C, Barry ST, Robson CN, Critchlow SE, Wedge SR, Brooks AN.Mol Cancer Ther. 2013 Sep;12(9):1715-27. doi: 10.1158/1535-7163.MCT-12-1174. Epub 2013 Jul 16. PMID: 23861347 Free PMC Article5:Discovery of AZD3514, a small-molecule androgen receptor downregulator for treatment of advanced prostate cancer. Bradbury RH, Acton DG, Broadbent NL, Brooks AN, Carr GR, Hatter G, Hayter BR, Hill KJ, Howe NJ, Jones RD, Jude D, Lamont SG, Loddick SA, McFarland HL, Parveen Z, Rabow AA, Sharma-Singh G, Stratton NC, Thomason AG, Trueman D, Walker GE, Wells SL, Wilson J, Wood JM.Bioorg Med Chem Lett. 2013 Apr 1;23(7):1945-8. doi: 10.1016/j.bmcl.2013.02.056. Epub 2013 Feb 21. PMID: 23466225