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| 10mg |
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| 25mg |
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UT-34 (UT34) is a novel, selective, and orally bioavailable pan-androgen receptor (AR) antagonist and also a selective androgen receptor degrader (SARD) with anti-prostate cancer activity. It inhibits wild-type, F876L and W741L AR with IC50s of 211.7 nM, 262.4 nM and 215.7 nM, respectively. UT-34 binds to ligand-binding domain (LBD) and function-1 (AF-1) domains and requires ubiquitin proteasome pathway to degrade the AR.
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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].
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| 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].
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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. |
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| 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 . |
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| References |
[1]. Ponnusamy S, et al. Orally Bioavailable Androgen Receptor Degrader, Potential Next-Generation Therapeutic for Enzalutamide-Resistant Prostate Cancer. Clin Cancer Res. 2019 Nov 15;25(22):6764-6780.
[2]. Stone L. UT-34: a promising new AR degrader. Nat Rev Urol. 2019 Nov;16(11):640. |
| Molecular Formula |
C15H12F4N4O2
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|---|---|
| Molecular Weight |
356.274996757507
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| CAS # |
2168525-92-4
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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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| 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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