| Size | Price | Stock | Qty |
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| Targets |
SIRT1
Targets mutant p53 protein via SIRT1 activation. By activating SIRT1, YK-3-237 reduces the acetylation of mutant p53, which promotes its degradation and reduces its oncogenic gain-of-function activities. It also targets tubulin by inhibiting colchicine binding in a concentration-dependent manner, contributing to its anti-proliferative effects via G2/M cell cycle arrest. |
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| ln Vitro |
At submicromolar concentrations, YK-3-237 demonstrates anti-proliferative activity against the majority of tested breast cancer cell lines. Breast cancer cell lines expressing mtp53 are specifically inhibited by YK-3-237[1]. With IC50s of 0.160±0.043, YK-3-237 inhibits the growth of HS578T, MDA-MB-453, SUM1315MO2, SUM149PT, BT549, MDA-MB-231, MDA-MB-436, MDA-MB-468, and HCC1937, which are triple-negative breast cancers. Luminal T47D, MCF7, and ZR-75-1 have IC50s of 1.573±0.370, 2.402±0.256, and 3.822±0.967 µM, respectively. HER2 BT474 and SK-BR-3 are inhibited by YK-3-237, with IC50s of 1.249±0.372 and 0.346±0.066 µM, respectively[1]. In TNBC cell lines, YK-3-237 (0.01-10 µM; 24 hours) deacetylates mtp53[1]. When NRK-49F cells are used to activate renal interstitial fibroblasts, YK-3-237 is a powerful activator of Sirt1[2]. When cells are exposed to YK-3-237, they also exhibit a dose-dependent reduction in the expression of α-SMA and fibronectin, with the highest inhibition observed at 10 μM [2].
At submicromolar concentrations, YK-3-237 demonstrates anti-proliferative activity against the majority of tested breast cancer cell lines, with specific inhibition of mtp53-expressing cell lines. It inhibits cell growth in a panel of leukemia, non-small cell lung, colon, CNS, melanoma, ovarian, renal, prostate, and breast cancer cell lines (GI50s = <0.01-20.9 microM). It induces PARP-dependent apoptotic cell death and arrests the cell cycle at G2/M phase. |
| ln Vivo |
In vivo activity data is not extensively reported. YK-3-237 has shown anti-tumor activity in preclinical studies of triple-negative breast cancer. As a SIRT1 activator targeting mtp53, it reduces the level of mutant p53 protein, which leads to decreased tumor cell proliferation. Further in vivo studies are needed to fully characterize its anti-tumor efficacy in animal models.
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| Enzyme Assay |
Cell-free SIRT1 deacetylase assays are performed using purified recombinant human SIRT1 enzyme and a fluorogenic substrate (Ac-Lys-AMC). The enzyme is incubated with substrate, NAD+ (200 microM), and varying YK-3-237 concentrations (0.1-100 microM) in assay buffer (50 mM Tris-HCl, pH 8.0, 137 mM NaCl, 2.7 mM KCl, 1 mM MgCl2) for 30 min at 37degC. Developer containing trichostatin A and nicotinamide is added, and fluorescence is measured (Ex/Em=360/460 nm) to calculate SIRT1 activation. Tubulin binding inhibition is assessed by colchicine displacement assay.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: BT549, MDA-MB-468, HS578T, SUM149PT Tested Tested Concentrations: 0, 0.01, 0.03, 0.1, 0.3, 1, 3, 10 µM Incubation Duration: 24 hrs (hours) Experimental Results: diminished both the acetylation of K382 and the level of mtp53 in a dose-dependent manner in mtp53 TNBC cell lines. Breast cancer cell lines (MDA-MB-231, HS578T, MCF7) are cultured in DMEM with 10% FBS. Cells are seeded in 96-well plates and treated with YK-3-237 (0.01-50 microM) for 48-72 h. Cell viability is measured by MTT or CellTiter-Glo assay. Mutant p53-expressing lines (HS578T, MDA-MB-231) are specifically inhibited with IC50 values of 0.160+/-0.043-0.5 microM. Cell cycle analysis is performed by propidium iodide staining and flow cytometry. Apoptosis is assessed by PARP cleavage and Annexin V/PI staining. |
| Animal Protocol |
No specific animal studies for YK-3-237 are publicly available. For a SIRT1 activator targeting mtp53, potential in vivo models include subcutaneous xenografts of triple-negative breast cancer cells (e.g., MDA-MB-231 or HS578T) in immunocompromised mice (nude or SCID mice). YK-3-237 would likely be administered intraperitoneally (10-50 mg/kg) or orally daily for 2-3 weeks, with endpoints including tumor volume measurement, tumor weight at sacrifice, and immunohistochemical analysis of p53, SIRT1, and acetylation status.
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| ADME/Pharmacokinetics |
Detailed PK data for YK-3-237 is not publicly available. YK-3-237 has a molecular weight of 372.18, formula C1₉H21BO₇, and purity ≥95%. As a boronic acid chalcone analog, it may have moderate stability in vivo. Solubility and formulation details are not publicly available. Standard PK parameters (half-life, clearance, bioavailability) would need to be determined experimentally.
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| Toxicity/Toxicokinetics |
No toxicity data is publicly available for YK-3-237. As a SIRT1 activator, potential safety concerns could include SIRT1-mediated effects on metabolism, aging, and cell survival, as SIRT1 has both tumor suppressor and tumor promoter functions depending on context. As a tubulin-binding agent (combretastatin analog), it could cause vascular toxicity and neurotoxicity similar to other tubulin-targeting agents, though no specific data is available.
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| References |
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| Additional Infomation |
SIRT1 activator; structure can be found in the first reference.
YK-3-237 is a research chemical not approved for clinical use. It is an important tool for studying the role of mutant p53 in cancer, particularly in triple-negative breast cancer (TNBC), which frequently harbors mtp53 mutations and has limited treatment options. By targeting mtp53 through SIRT1 activation, YK-3-237 provides a novel approach to eliminate the oncogenic gain-of-function activities of mutant p53, making it a valuable candidate for further anti-cancer drug development. |
| Molecular Formula |
C19H21BO7
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| Molecular Weight |
372.18
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| Exact Mass |
372.138
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| CAS # |
1215281-19-8
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| PubChem CID |
24881094
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| Appearance |
White to light yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
616.2±65.0 °C at 760 mmHg
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| Flash Point |
326.5±34.3 °C
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| Vapour Pressure |
0.0±1.9 mmHg at 25°C
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| Index of Refraction |
1.577
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| LogP |
3.52
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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 |
8
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| Heavy Atom Count |
27
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| Complexity |
484
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| Defined Atom Stereocenter Count |
0
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| SMILES |
B(C1=C(C=CC(=C1)/C=C/C(=O)C2=CC(=C(C(=C2)OC)OC)OC)OC)(O)O
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| InChi Key |
AKNGHUAJAODDJA-FNORWQNLSA-N
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| InChi Code |
InChI=1S/C19H21BO7/c1-24-16-8-6-12(9-14(16)20(22)23)5-7-15(21)13-10-17(25-2)19(27-4)18(11-13)26-3/h5-11,22-23H,1-4H3/b7-5+
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| Chemical Name |
[2-methoxy-5-[(E)-3-oxo-3-(3,4,5-trimethoxyphenyl)prop-1-enyl]phenyl]boronic acid
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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: 100 mg/mL (268.69 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.72 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 25.0 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: ≥ 2.5 mg/mL (6.72 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6869 mL | 13.4344 mL | 26.8687 mL | |
| 5 mM | 0.5374 mL | 2.6869 mL | 5.3737 mL | |
| 10 mM | 0.2687 mL | 1.3434 mL | 2.6869 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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