| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
| Targets |
IC50: 211.7 nM (Wild-type AR); 262.4 nM (F876L AR); and 215.7 nM (W741L AR)[1]
UT-34 targets the androgen receptor (AR), a nuclear receptor that mediates the effects of androgens such as testosterone and dihydrotestosterone. As a pan-antagonist and degrader, UT-34 inhibits AR signaling through two distinct mechanisms: it competitively binds to the AR ligand-binding domain to block androgen-induced activation, and it promotes AR protein degradation. The compound is effective against wild-type AR and clinically relevant AR mutants, including F876L-AR and W741L-AR, which are associated with resistance to first-line antiandrogens. |
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| ln Vitro |
The expression of PSA and FKBP5, as well as the proliferation of LNCaP cells, are inhibited by UT-34 (3-10 μM; 24 hours); the largest effect is seen at 10 μM [1]. The effect starts at 100 nM. AR levels at 1000 nM in LNCaP cells decreased after treatment with UT-34 (0.1–10 μM; 24 hours) [1]. AR protein levels were downregulated when ZR-75-1 cells were maintained in serum growth media containing UT-34, but not the levels of progesterone receptors (PR) or estrogen receptors (ER). Moreover, UT-34 promoted downregulation of AR but not GR in MDA-MB-453 breast cancer cells that expressed both glucocorticoid receptor (GR) and AR [1]. AR and AR-V7 can be effectively degraded by UT-34. For a whole day, either 10 ng/mL doxycycline or 0.1 nM R1881, or both, were added to LNCaP-ARV7 cells. UT-34 inhibits the expression of EDN2, which is induced by doxycycline, and UT-34 also inhibits the expression of the FKBP5 gene, which is activated by R1881, [1].
UT-34 demonstrates potent in vitro activity as an AR antagonist and degrader. It inhibits wild-type AR with an IC50 of 203.46 nM (or 211.7 nM), T877A AR with an IC50 of 80.78 nM, and W741L AR with an IC50 of 94.17 nM (or 215.7 nM). It also inhibits the F876L-AR mutant with an IC50 of 262.4 nM. The compound's dual mechanism—antagonism and degradation—provides more complete suppression of AR signaling compared to antagonists alone. These in vitro activities confirm its potential for treating AR-driven prostate cancer, including CRPC. |
| ln Vivo |
Seminal vesicle weight was decreased by 10%–20% and 50%–60%, respectively, by UT-34 at 20 and 40 mg/kg (20–40 mg/kg; oral; daily; 14 days; NSG mice) [1]. Rat prostate and seminal vesicles, as well as enzalutamide-resistant castration-resistant prostate cancer (CRPC) xenografts, are examples of androgen-dependent tissues whose proliferation is inhibited by UT-34. In rats with intact immunocompromised immune systems, UT-34 also causes tumor regression [1].
UT-34 has demonstrated in vivo anti-prostate cancer efficacy in preclinical models. As an orally active compound, it can be administered conveniently in animal studies. The compound effectively degrades AR in tumor tissues and inhibits androgen-driven tumor growth. Its activity against AR mutants associated with resistance suggests it may overcome resistance to first-line antiandrogens. In vivo studies have confirmed that UT-34 exhibits good antitumor activity. The compound is a promising candidate for the treatment of castration-resistant prostate cancer. |
| Enzyme Assay |
In vitro receptor binding assays for UT-34 involve measuring its affinity for the androgen receptor (AR). Competitive binding assays using radiolabeled androgens (e.g., [3H]-R1881) are commonly used. The compound is incubated with AR and the radioligand, and the displacement is measured to calculate the binding affinity. Transactivation assays using AR-responsive luciferase reporters are used to measure functional antagonism. AR degradation is assessed by Western blot or ELISA in cells treated with the compound. These assays confirm the compound's mechanism as a potent AR antagonist and degrader.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: LNCaP cells Tested Concentrations: 3 µM, 10 µM Incubation Duration: 24 hrs (hours) Experimental Results: Inhibited the expression of PSA and FKBP5 and growth of LNCaP cells starting from 100 nM with maximum effect observed at 10 μM. Western Blot Analysis[1] Cell Types: LNCaP cells Tested Concentrations: 0.1 µM, 1 µM, 10 µM Incubation Duration: 24 hrs (hours) Experimental Results: Resulted in a reduction of AR levels at 1000 nM. In vitro cellular assays for UT-34 are conducted in AR-positive prostate cancer cell lines such as LNCaP, VCaP, and 22Rv1. Cells are treated with the compound at various concentrations, and AR transcriptional activity is measured using luciferase reporter assays. AR protein levels are measured by Western blot to assess degradation. Cell proliferation is measured using MTT or CellTiter-Glo assays. The compound's effects on AR target gene expression (e.g., PSA, KLK2) are assessed by qPCR. These assays characterize the compound's activity as a SARD and its potential for treating CRPC. |
| Animal Protocol |
Animal/Disease Models: Non obese diabetic/severe combined immunodeficiency Gamma (NSG) mice injected with MR49F cells[1]
Doses: 20 mg/kg or 40 mg/kg Route of Administration: Oral administration; daily; for 14 days Experimental Results: decreased the seminal vesicle weight . In vivo animal experiments with UT-34 are conducted in mouse xenograft models of prostate cancer, including models of castration-resistant prostate cancer (CRPC). Immunodeficient mice are engrafted with AR-positive prostate cancer cells (e.g., LNCaP, VCaP, or 22Rv1). UT-34 is administered orally at varying doses. Tumor growth is measured over time, and tumor tissues are harvested for analysis of AR levels and signaling pathways. Pharmacodynamic studies are performed to confirm AR degradation and target engagement. These studies support the development of UT-34 for prostate cancer therapy. |
| ADME/Pharmacokinetics |
UT-34 is an orally available compound with favorable pharmacokinetic properties. It has good oral bioavailability and is suitable for once-daily dosing. The compound has a molecular weight of 356.27 and is soluble in DMSO (250 mg/mL with ultrasonication). Its half-life and tissue distribution have been characterized in preclinical studies. The compound is metabolized in the liver and excreted via biliary and renal routes. Its pharmacokinetic profile supports its use in preclinical models of prostate cancer. The compound should be stored at -20°C.
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| Toxicity/Toxicokinetics |
UT-34 has been evaluated for safety in preclinical studies. The compound is generally well-tolerated at therapeutic doses. As an AR antagonist and degrader, its toxicity profile may include effects related to androgen deprivation, such as fatigue, loss of libido, and hot flashes. The compound is intended for research use only and is not approved for human therapeutic use. Standard laboratory safety precautions should be followed when handling this compound. Further toxicity studies would be required to support any potential clinical development.
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| References | |
| Additional Infomation |
UT-34 is a potent, selective, and orally active second-generation pan-androgen receptor (AR) antagonist and degrader. It is also known as (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-fluoro-1H-pyrazol-1-yl)-2-hydroxy-2-methylpropanamide. UT-34 is an investigational SARD designed to overcome resistance to conventional AR antagonists. It is effective against wild-type AR and clinically relevant AR mutants. The compound is available in high purity (98%) for research applications. Its dual mechanism of AR antagonism and degradation makes it a promising candidate for the treatment of castration-resistant prostate cancer.
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| Molecular Formula |
C15H12F4N4O2
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|---|---|
| Molecular Weight |
356.274996757507
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| Exact Mass |
356.089
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| CAS # |
2168525-92-4
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| PubChem CID |
132214622
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| Appearance |
White to off-white solid powder
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| LogP |
1.3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
549
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| Defined Atom Stereocenter Count |
1
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| SMILES |
FC1C=NN(C=1)C[C@](C(NC1C=CC(C#N)=C(C(F)(F)F)C=1)=O)(C)O
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| InChi Key |
YDRMSDHDYRAUBR-AWEZNQCLSA-N
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| InChi Code |
InChI=1S/C15H12F4N4O2/c1-14(25,8-23-7-10(16)6-21-23)13(24)22-11-3-2-9(5-20)12(4-11)15(17,18)19/h2-4,6-7,25H,8H2,1H3,(H,22,24)/t14-/m0/s1
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| Chemical Name |
(2S)-N-[4-cyano-3-(trifluoromethyl)phenyl]-3-(4-fluoropyrazol-1-yl)-2-hydroxy-2-methylpropanamide
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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 |
| 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) |
DMSO : ~250 mg/mL (~701.71 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.84 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 20.8 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: ≥ 2.08 mg/mL (5.84 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), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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: ≥ 2.08 mg/mL (5.84 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 | 2.8068 mL | 14.0339 mL | 28.0678 mL | |
| 5 mM | 0.5614 mL | 2.8068 mL | 5.6136 mL | |
| 10 mM | 0.2807 mL | 1.4034 mL | 2.8068 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.
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