WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H204540
CAS#: 1240299-33-5 (free base)
Description: AZD-3514 is a potent androgen receptor downregulator with potential anticancer cancer activity. AZD3514 is being evaluated in a Phase I clinical trial in patients with castrate-resistant prostate cancer.
Hodoodo Cat#: H204540
Name: AZD-3514
CAS#: 1240299-33-5 (free base)
Chemical Formula: C25H32F3N7O2
Exact Mass: 519.26
Molecular Weight: 519.560
Elemental Analysis: C, 57.79; H, 6.21; F, 10.97; N, 18.87; O, 6.16
Related CAS #: 1240299-36-8 (maleate) 1240299-33-5 (free base)
Synonym: AZD3514; AZD 3514; AZD-3514.
IUPAC/Chemical Name: 1-(4-(2-(4-(1-(3-(trifluoromethyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)piperidin-4-yl)phenoxy)ethyl)piperazin-1-yl)ethanone
InChi Key: JMEYDSHPKCSIJC-UHFFFAOYSA-N
InChi Code: 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
SMILES Code: CC(N1CCN(CCOC2=CC=C(C3CCN(C4=NN5C(CC4)=NN=C5C(F)(F)F)CC3)C=C2)CC1)=O
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >5 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info: AZD3514 is currently in Phase I trail. This trial is looking at a new drug called AZD3514 for men who have prostate cancer that has spread to other parts of the body and is no longer responding to hormone therapy. Doctors often use hormone therapy to treat prostate cancer. This may keep it under control for long periods of time. But researchers are looking for treatments that will help men who have prostate cancer that stops responding to hormone therapy. Prostate cancer needs the hormone testosterone to grow. The testosterone locks into receptors on the cancer cells. AZD3514 works by breaking down these receptors so that testosterone canÂ’t tell the prostate cancer cells to grow.
| Biological target: | AZD3514 is a potent and oral androgen receptor downregulator with Ki of 2.2 μM and has ability of reducing AR protein expression. |
| In vitro activity: | AZD3514 and AR antagonist Enzalutamide inhibited DHT driven proliferation of LNCaP cells in a dose-dependent manner (Fig.2A-B). The DHT driven proliferation of LAPC4 cells was also inhibited by 10 μM of AZD3514 (Fig. 2C). AZD3514 inhibited the ligand-driven expression of known AR regulated genes PSA and TMPRSS2 in both LNCaP and LAPC4 cells (Fig. 2D-G). In LNCaP cells inhibition of PSA and TMPRSS2 expression by AZD3514 was shown under a range of DHT conditions (0-10 nM) (Fig. 2D and E). AZD3514 was less potent with increasing DHT concentrations, although near complete inhibition of PSA and TMPRSS2 was observed with 10 μM AZD3514 at all concentrations. Importantly, the basal expression of PSA, and TMPRSS2 in LNCaP cells, and PSA in LAPC4s cells, observed in the absence of DHT was also reduced by treatment with AZD3514 (Fig. 2D-G; data re-plotted in Sup. Fig. 1A-D to provide greater clarity). In LNCaP cells AZD3514 inhibited ligand driven PSA and TMPRSS2 expression within 2-4 hours of treatment (Sup. Fig. 1E-G). Reference: Mol Cancer Ther. 2013 Sep; 12(9): 1715–1727. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3769207/ |
| In vivo activity: | Comparably to lead compound 1,14 compounds 6b, 10 and 12 (AZD-3514) dosed orally at 50–100 mg/kg twice daily in the Hershberger model for 7 days caused a significant inhibition of testosterone-induced growth of rat seminal vesicles (data not shown), the magnitude of effect being comparable to that seen with bicalutamide dosed at 2 mg/kg. Analysis of plasma samples 18 h subsequent to administration of the final dose showed free concentrations comparable to the IC50 for nuclear AR downregulation. Reference: Bioorg Med Chem Lett. 2013 Apr 1;23(7):1945-8. https://pubmed.ncbi.nlm.nih.gov/23466225/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 100.0 | 192.47 | |
| Ethanol | 100.0 | 192.47 |
The following data is based on the product molecular weight 519.56 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. 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. AZD3514: a small molecule that modulates androgen receptor signaling and function in vitro and in vivo. Mol Cancer Ther. 2013 Sep;12(9):1715-27. doi: 10.1158/1535-7163.MCT-12-1174. Epub 2013 Jul 16. PMID: 23861347; PMCID: PMC3769207. 2. 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. Discovery of AZD3514, a small-molecule androgen receptor downregulator for treatment of advanced prostate cancer. 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. |
| In vitro protocol: | 1. 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. AZD3514: a small molecule that modulates androgen receptor signaling and function in vitro and in vivo. Mol Cancer Ther. 2013 Sep;12(9):1715-27. doi: 10.1158/1535-7163.MCT-12-1174. Epub 2013 Jul 16. PMID: 23861347; PMCID: PMC3769207. 2. 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. Discovery of AZD3514, a small-molecule androgen receptor downregulator for treatment of advanced prostate cancer. 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. |
| In vivo protocol: | 1. 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. AZD3514: a small molecule that modulates androgen receptor signaling and function in vitro and in vivo. Mol Cancer Ther. 2013 Sep;12(9):1715-27. doi: 10.1158/1535-7163.MCT-12-1174. Epub 2013 Jul 16. PMID: 23861347; PMCID: PMC3769207. 2. 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. Discovery of AZD3514, a small-molecule androgen receptor downregulator for treatment of advanced prostate cancer. 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. |
1: 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. Discovery of AZD3514, a small-molecule androgen receptor downregulator for treatment of advanced prostate cancer. Bioorg Med Chem Lett. 2013 Apr 1;23(7):1945-8. doi: 10.1016/j.bmcl.2013.02.056. Epub 2013 Feb 21. PubMed PMID: 23466225.
