Synonym
(S)-UT 155; (S) UT-155; (S)-UT-155; UT155; UT 155; UT-155
IUPAC/Chemical Name
(S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(5-fluoro-1H-indol-1-yl)-2-hydroxy-2-methylpropanamide
InChi Key
CFSAYQVTXBMPRF-IBGZPJMESA-N
InChi Code
InChI=1S/C20H15F4N3O2/c1-19(29,11-27-7-6-12-8-14(21)3-5-17(12)27)18(28)26-15-4-2-13(10-25)16(9-15)20(22,23)24/h2-9,29H,11H2,1H3,(H,26,28)/t19-/m0/s1
SMILES Code
O=C(NC1=CC=C(C#N)C(C(F)(F)F)=C1)[C@@](C)(O)CN2C=CC3=C2C=CC(F)=C3
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
Shelf Life
>3 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
Biological target:
UT-155 is a selective and potent androgen receptor (AR) antagonist, with a Ki of 267 nM for UT-155 binding to AR-LBD.
In vitro activity:
The effect of UT-155 on the protein level of closely related receptors, PR and estrogen receptor (ER) was tested in T47D breast cancer cells. Although UT-155 blocked PR-dependent transactivation (Figure 1), it had no effect on PR or ER protein levels in T47D cells (Figure 3D). The effect of UT-155 on glucocorticoid receptor (GR) protein levels was tested in PC-3 cells transiently transfected with an expression construct. While UT-155 inhibited the AR protein under similar conditions, it had no effect on GR (Figure S2A). Second, the effect of UT-155 on the fluorescence signal emitted by GFP-AR, GFP, or GFP-ANGPTL4, a protein that has no homology to nuclear receptors, was tested in HeLa cells. Treatment of HeLa cells transfected with the GFP-tagged constructs with 10 μM UT-155 resulted in down-regulation of the GFP signal in GFP-AR-transfected cells, but not in cells expressing GFP or GFP-ANGPTL4 (Figure S2B). Additionally, mass spectrometry was performed in LNCaP cells treated with vehicle or 10 μM UT-155. The results show that UT-155 did not inhibit the expression of the proteins identified, other than the AR. Some of the proteins identified are shown in Figure S2C. Finally, a study to determine the cross-reactivity of UT-155 with a panel of kinases demonstrated no significant inhibition of kinase activity. These results provide strong evidence for the selectivity of UT-155 to the AR.
Reference: Cancer Res. 2017 Nov 15;77(22):6282-6298. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/28978635/
In vivo activity:
To determine the effects in vivo, UT-155 was tested in xenograft models. UT-155 inhibited the growth of the LNCaP tumors with a 65% tumor growth inhibition (TGI) (Figure 7C). Consistent with the inhibition of tumor volume, tumor weights and tumor PSA were also significantly lower by 50–75% in UT-155-treated animals (Figure 7C). UT-155 significantly inhibited the growth of 22RV1 xenograft by 53% (Figure 7D). In the measurement of drug concentration in the tumors to determine the drug exposure, UT-155 was extracted from tumors and was detected by mass spectrometry. UT-155 accumulated in the tumors and the concentration of 562 nM was above its IC50 concentration (Figure S8F). Consistent with the observations made in 22RV1 xenografts, UT-155 inhibited the growth of Pr-3001 by 40–60% over the course of 14 days (Figure 7E).
Reference: Cancer Res. 2017 Nov 15;77(22):6282-6298. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/28978635/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
100.0 |
246.70 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
405.35
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 |
In vitro protocol:
1. Ponnusamy S, Coss CC, Thiyagarajan T, Watts K, Hwang DJ, He Y, Selth LA, McEwan IJ, Duke CB, Pagadala J, Singh G, Wake RW, Ledbetter C, Tilley WD, Moldoveanu T, Dalton JT, Miller DD, Narayanan R. Novel Selective Agents for the Degradation of Androgen Receptor Variants to Treat Castration-Resistant Prostate Cancer. Cancer Res. 2017 Nov 15;77(22):6282-6298. doi: 10.1158/0008-5472.CAN-17-0976. Epub 2017 Oct 4. PMID: 28978635; PMCID: PMC5890913.
In vivo protocol:
1. Ponnusamy S, Coss CC, Thiyagarajan T, Watts K, Hwang DJ, He Y, Selth LA, McEwan IJ, Duke CB, Pagadala J, Singh G, Wake RW, Ledbetter C, Tilley WD, Moldoveanu T, Dalton JT, Miller DD, Narayanan R. Novel Selective Agents for the Degradation of Androgen Receptor Variants to Treat Castration-Resistant Prostate Cancer. Cancer Res. 2017 Nov 15;77(22):6282-6298. doi: 10.1158/0008-5472.CAN-17-0976. Epub 2017 Oct 4. PMID: 28978635; PMCID: PMC5890913.
1: Montgomery EJ, Xing E, Campbell MJ, Li PK, Blachly JS, Tsung A, Coss CC. Constitutively Active Androgen Receptor in Hepatocellular Carcinoma. Int J Mol Sci. 2022 Nov 9;23(22):13768. doi: 10.3390/ijms232213768. PMID: 36430245; PMCID: PMC9699340.
2: He Y, Hwang DJ, Ponnusamy S, Thiyagarajan T, Mohler ML, Narayanan R, Miller DD. Exploration and Biological Evaluation of Basic Heteromonocyclic Propanamide Derivatives as SARDs for the Treatment of Enzalutamide-Resistant Prostate Cancer. J Med Chem. 2021 Aug 12;64(15):11045-11062. doi: 10.1021/acs.jmedchem.1c00439. Epub 2021 Jul 16. PMID: 34269581; PMCID: PMC8503816.
3: He Y, Hwang DJ, Ponnusamy S, Thiyagarajan T, Mohler ML, Narayanan R, Miller DD. Pyrazol-1-yl-propanamides as SARD and Pan-Antagonists for the Treatment of Enzalutamide-Resistant Prostate Cancer. J Med Chem. 2020 Nov 12;63(21):12642-12665. doi: 10.1021/acs.jmedchem.0c00943. Epub 2020 Oct 23. PMID: 33095584; PMCID: PMC7703681.
4: Ponnusamy S, Coss CC, Thiyagarajan T, Watts K, Hwang DJ, He Y, Selth LA, McEwan IJ, Duke CB, Pagadala J, Singh G, Wake RW, Ledbetter C, Tilley WD, Moldoveanu T, Dalton JT, Miller DD, Narayanan R. Novel Selective Agents for the Degradation of Androgen Receptor Variants to Treat Castration-Resistant Prostate Cancer. Cancer Res. 2017 Nov 15;77(22):6282-6298. doi: 10.1158/0008-5472.CAN-17-0976. Epub 2017 Oct 4. PMID: 28978635; PMCID: PMC5890913.
5: Sharman R. European Association of Urology - 32nd Annual Congress (March 24-28, 2017 - London, UK). Drugs Today (Barc). 2017 Apr;53(4):257-263. doi: 10.1358/dot.2017.53.4.2630607. PMID: 28492293.
