| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| Other Sizes |
| Targets |
YHO-13351 is a prodrug that targets the ATP-binding cassette (ABC) transporter BCRP (ABCG2). Following administration, it is rapidly converted to its active form, YHO-13177. YHO-13177 potently inhibits BCRP, blocking its efflux function. This prevents cancer cells from pumping out chemotherapeutic agents, leading to their increased intracellular accumulation and enhanced cytotoxic effects.
|
|---|---|
| ln Vitro |
In vitro, YHO-13351 itself is a prodrug and its activity is mediated by its active metabolite, YHO-13177. YHO-13177 has demonstrated potent reversal of BCRP-mediated drug resistance across various cancer cell lines. It effectively sensitizes resistant cells to chemotherapeutic agents that are BCRP substrates, such as SN-38, mitoxantrone, and topotecan. In cell lines like HCT116/BCRP, A549/SN4, NCI-H460, and NCI-H23, YHO-13177 potentiates the cytotoxicity of these drugs.
|
| ln Vivo |
In vivo, YHO-13351 is rapidly converted to YHO-13177 after oral or intravenous administration in mice. This conversion allows YHO-13351 to function as an orally available prodrug of the active BCRP inhibitor. By inhibiting BCRP, it can reverse drug resistance and enhance the efficacy of co-administered chemotherapeutic agents in vivo. For example, it has been shown to potentiate the antitumor activity of irinotecan.
|
| Enzyme Assay |
The in vitro BCRP inhibition assay for YHO-13351 is performed using its active metabolite, YHO-13177. The compound is incubated with membrane vesicles from cells overexpressing BCRP and a fluorescent or radiolabeled substrate, such as [3H]-mitoxantrone or pheophorbide A. The accumulation of the substrate inside the vesicles is measured, and the IC50 is calculated from the inhibition curve.
|
| Cell Assay |
In vitro cell culture studies for YHO-13351 utilize BCRP-overexpressing cancer cell lines, such as HCT116/BCRP or A549/SN4. Cells are treated with YHO-13351 (which is converted to YHO-13177 in culture) in the presence of a chemotherapeutic agent that is a BCRP substrate. Cell viability is assessed using an MTT or CellTiter-Glo assay. The compound's ability to reverse drug resistance is measured by comparing the IC50 of the chemotherapeutic agent in the presence and absence of YHO-13351.
|
| Animal Protocol |
In vivo animal experiments for YHO-13351 are performed in xenograft models using BCRP-overexpressing tumors. The compound is administered orally or intravenously, often in combination with a chemotherapeutic agent such as irinotecan. Tumor growth is monitored, and the compound's ability to enhance the antitumor activity of the chemotherapeutic agent is assessed. The pharmacokinetics of YHO-13351 and its conversion to YHO-13177 are also studied.
|
| ADME/Pharmacokinetics |
YHO-13351 free base has a molecular formula of C26H33N3O4S and a molecular weight of 483.62 g/mol. It is a solid powder that is soluble in DMSO. It is typically stored at -20°C. As a water-soluble prodrug, it is designed for oral administration, with good bioavailability. Its stability is maintained under recommended storage conditions.
|
| Toxicity/Toxicokinetics |
Toxicological data for YHO-13351 are limited, as it is a research compound. It is not intended for human use. Comprehensive toxicity studies have not been reported. Standard safety precautions for handling chemical reagents should be followed. Its potent BCRP inhibition suggests it could have significant effects on drug disposition and toxicity.
|
| References |
|
| Additional Infomation |
YHO-13351 free base is a research compound with no clinical approval. It is a valuable tool for studying the role of BCRP in multidrug resistance and for developing strategies to overcome it. It is used in drug discovery programs to explore the therapeutic potential of BCRP inhibitors in cancer chemotherapy. Its prodrug design allows for oral administration, making it a convenient tool for in vivo studies.
|
| Molecular Formula |
H3N
|
|---|---|
| Molecular Weight |
17.0305197238922
|
| Exact Mass |
483.219
|
| CAS # |
912288-64-3
|
| Related CAS # |
YHO-13351;1346753-00-1
|
| PubChem CID |
11964785
|
| Appearance |
Yellow to orange solid powder
|
| Density |
1.2±0.1 g/cm3
|
| Boiling Point |
627.1±55.0 °C at 760 mmHg
|
| Flash Point |
333.1±31.5 °C
|
| Vapour Pressure |
0.0±1.8 mmHg at 25°C
|
| Index of Refraction |
1.594
|
| LogP |
5.17
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
11
|
| Heavy Atom Count |
34
|
| Complexity |
727
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CCN(CC)CC(=O)OC1CCN(CC1)C2=CC=C(S2)/C=C(\C#N)/C3=CC(=C(C=C3)OC)OC
|
| InChi Key |
STLNUMIUXISGQQ-HMMYKYKNSA-N
|
| InChi Code |
InChI=1S/C26H33N3O4S/c1-5-28(6-2)18-26(30)33-21-11-13-29(14-12-21)25-10-8-22(34-25)15-20(17-27)19-7-9-23(31-3)24(16-19)32-4/h7-10,15-16,21H,5-6,11-14,18H2,1-4H3/b20-15+
|
| Chemical Name |
[1-[5-[(Z)-2-cyano-2-(3,4-dimethoxyphenyl)ethenyl]thiophen-2-yl]piperidin-4-yl] 2-(diethylamino)acetate
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~206.77 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.17 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 58.7199 mL | 293.5995 mL | 587.1991 mL | |
| 5 mM | 11.7440 mL | 58.7199 mL | 117.4398 mL | |
| 10 mM | 5.8720 mL | 29.3600 mL | 58.7199 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
