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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
UT-155 is a potent and selective androgen receptor (AR) degrader (SARD) that, at submicromolar doses, significantly decreases the activity of wild-type and splice variant isoforms of AR. Two of these SARDs (UT-69 and UT-155) also bind the carboxy-terminal ligand binding domain. Three SARDs (UT-69, UT-155, and (R)-UT-155) bind the amino-terminal transcriptional activation domain AF-1, which has not previously been targeted for degradation. All three SARDs demonstrated higher inhibitory potency than the authorized AR antagonists, degrading wild-type AR and inhibiting AR function despite having distinct mechanisms of action. All of these findings point to a novel class of potential next-generation treatments for the treatment of advanced prostate cancer. The growth of prostate cancer is mediated by the androgen receptor (AR) at all stages of the disease's progression, including advanced stage castration-resistant disease caused by abnormal splice variants (AR-SV). Different from other steroid receptors, which are usually ubiquitinated and broken down by proteasomes following ligand binding, AR is stabilized by androgens. Consequently, in order to effectively treat advanced prostate cancer, agents that can degrade variant isoforms over time must be developed.
| Targets |
AR-LBD (Ki = 267 nM)
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| ln Vitro |
UT-155 binds at a Ki of 267 nM to the AR-LBD. UT-155 has 6–10 times the potency of enzalutamide in inhibiting the wildtype AR transactivation induced by R1881. Enzalutamide is two times less effective against the W742L mutant AR than it is against the wild type AR, even though UT-155 antagonizes both wildtype and mutant ARs in a comparable way. When applied to LNCaP cells, UT-155 has 5–10 times more potency than enzalutamide in inhibiting 0.1 nM R1881-induced PSA and FKBP5 gene expression between 10 and 100 nM[1].
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| ln Vivo |
As anticipated, enzalutamide has no effect on the growth of the 22RV1 tumors, but UT-155 dramatically inhibits the growth of the 22RV1 xenograft by 53%, which is consistent with the anti-proliferative effects in vitro. In animals treated with UT-155, there is a significant decrease in tumor weights, PSA, and the expression of AR and AR-SV [1].
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| Enzyme Assay |
UT-155 is a selective androgen receptor (AR) antagonist, with a Ki of 267 nM for AR-RBD. In addition to competing with one another for binding to the LBD, UT-69 and UT-155 also lower AR protein levels after 24 hours, which is similar to the reported decline in transcriptional activity. We assessed the effect of the SARDs on the pre-mRNA of the hormone-rapidly induced NDRG1 and MT2A genes to ascertain whether the reduction in expression was necessary to inhibit AR activity or whether the competitive displacement of androgen from the LBD is sufficient to inhibit transcriptional activity.
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| Cell Assay |
Cells were cultured in 96-well plates according to the cell line, with different densities and serum-containing media. Viability was assessed using the cell-titer glo assay (Promega, Madison, WI) or sulforhodamine B (SRB), as shown in the figures.
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| Animal Protocol |
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| References |
| Molecular Formula |
C20H15F4N3O2
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| Molecular Weight |
405.345618486404
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| Exact Mass |
405.11
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| Elemental Analysis |
C, 59.26; H, 3.73; F, 18.75; N, 10.37; O, 7.89
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| CAS # |
2031161-35-8
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| Related CAS # |
(R)-UT-155;2031161-54-1
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| PubChem CID |
122640156
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| Appearance |
White to off-white solid powder
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| LogP |
3.1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
29
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| Complexity |
664
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C[C@](CN1C=CC2=C1C=CC(=C2)F)(C(=O)NC3=CC(=C(C=C3)C#N)C(F)(F)F)O
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| InChi Key |
CFSAYQVTXBMPRF-IBGZPJMESA-N
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| 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
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| Chemical Name |
(2S)-N-[4-cyano-3-(trifluoromethyl)phenyl]-3-(5-fluoroindol-1-yl)-2-hydroxy-2-methylpropanamide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.17 mg/mL (5.35 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.17 mg/mL (5.35 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.17 mg/mL (5.35 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4670 mL | 12.3350 mL | 24.6700 mL | |
| 5 mM | 0.4934 mL | 2.4670 mL | 4.9340 mL | |
| 10 mM | 0.2467 mL | 1.2335 mL | 2.4670 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 UT-155 and UT-69 inhibit AR function and reduce AR expression.Cancer Res.2017 Nov 15;77(22):6282-6298. |
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 Distinct requirements for UT-155 and UT-69 to inhibit the AR function.Cancer Res.2017 Nov 15;77(22):6282-6298. |
 UT-155 and UT-69 both promote degradation of the AR.Cancer Res.2017 Nov 15;77(22):6282-6298. |
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