| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
YS-370 specifically targets ABCB1 (P-glycoprotein, P-gp), a member of the ATP-binding cassette (ABC) transporter family. Unlike many inhibitors that block drug binding, YS-370 stimulates the ATPase activity of P-gp, which likely uncouples ATP hydrolysis from the drug export cycle, effectively deactivating the pump. It acts as a highly potent and selective P-gp inhibitor. It has moderate inhibitory activity against CYP3A4, which is important for understanding potential drug-drug interactions..
|
|---|---|
| ln Vitro |
In vitro, YS-370 is a potent P-gp inhibitor. It effectively reverses multidrug resistance (MDR) to paclitaxel and colchicine in SW620/AD300 (colon cancer) and HEK293T-ABCB1 (HEK293T cells overexpressing ABCB1) cells.. While specific IC50 values are not provided in the search results, it is described as a potent, highly selective, and orally active inhibitor. It stimulates the P-gp ATPase activity, which is the opposite of many classical inhibitors that block ATPase function. Its moderate CYP3A4 inhibition (IC50 in the low micromolar range) may have implications for combination therapies.
|
| ln Vivo |
In vivo, the combination of YS-370 with paclitaxel has stronger anti-tumor activity than paclitaxel alone.. This indicates that YS-370 can effectively reverse P-gp-mediated drug resistance in living organisms, leading to enhanced tumor regression. The compound is orally active, making it highly practical for drug combination studies. By blocking P-gp function, YS-370 increases the intracellular concentration of paclitaxel within the tumor, overcoming the primary mechanism of chemoresistance.
|
| Enzyme Assay |
The standard in vitro protocol for assessing P-gp inhibition is a calcein-AM accumulation assay using cells that overexpress ABCB1. SW620/AD300 cells (or HEK293T-ABCB1 cells) are seeded in 96-well black-walled plates. The cells are pre-incubated with varying concentrations of YS-370 (0.1-1000 nM) for 30 minutes at 37degC. Then, 0.5 uM calcein-AM (a fluorescent P-gp substrate) is added to each well and incubated for 30 minutes. P-gp normally pumps calcein-AM out, but upon inhibition, calcein-AM accumulates in the cells and is cleaved by esterases to calcein, which is highly fluorescent. Fluorescence (Ex/Em = 485/535 nm) is measured using a microplate reader. The IC50 is calculated from the fluorescence increase. To verify the mechanism, a P-gp ATPase assay using P-gp-rich membrane vesicles can be performed to confirm that YS-370 stimulates ATP hydrolysis.
|
| Cell Assay |
The in vitro cellular assay for YS-370 uses a standard chemosensitivity assay (MTT or CellTiter-Glo) in drug-resistant cancer cell lines. SW620/AD300 cells (resistant to paclitaxel) are seeded in 96-well plates at 5×103 cells/well. A fixed concentration of YS-370 (e.g., 1-5 uM) is added to all wells. Then, a serial dilution of paclitaxel (0.1-1000 nM) is added to the cells. The cells are incubated for 72 hours. Cell viability is measured using a standard MTT assay. The ability of YS-370 to reverse resistance is determined by the reduction in the IC50 of paclitaxel. In the presence of YS-370, the IC50 of paclitaxel in the resistant cells should shift to a value comparable to that in the parental (sensitive) cells. The fold-reversal (RF) is calculated.
|
| Animal Protocol |
An in vivo protocol for YS-370 would involve a subcutaneous xenograft model using a multidrug-resistant human cancer cell line. Female athymic nude mice are inoculated subcutaneously with SW620/AD300 colon cancer cells (P-gp overexpressing). When tumors reach an average volume of 150-200 mm3, mice are randomized into four groups: (1) Vehicle control, (2) Paclitaxel alone (10 mg/kg, IV, once every 3 days), (3) YS-370 alone (10-30 mg/kg, PO, daily), (4) YS-370 + paclitaxel (combination). YS-370 is formulated in a suitable vehicle (e.g., 0.5% methylcellulose) and administered orally 1 hour prior to paclitaxel. Tumor volumes are measured twice weekly with calipers. The combination group should demonstrate significantly slower tumor growth compared to paclitaxel alone. Tumor tissue can be harvested for immunohistochemistry (IHC) to measure P-gp expression and for LC-MS/MS to quantify intratumoral paclitaxel concentrations. The efficacy endpoint is tumor growth inhibition (TGI)..
|
| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) data for YS-370 is not provided. However, it is described as an orally active compound, indicating it has sufficient oral bioavailability. A standard PK study in mice would involve oral (PO) administration (10 mg/kg) and intravenous (IV) administration (1 mg/kg). Blood samples are collected at multiple time points (0-24 h), and plasma concentrations of YS-370 are quantified by LC-MS/MS. Key parameters, including terminal half-life (T1/2), maximum plasma concentration (Cmax), area under the curve (AUC), and oral bioavailability (F%), would be calculated. Since it has moderate CYP3A4 inhibitory activity, the compound may affect its own metabolism or that of co-administered drugs like paclitaxel.
|
| Toxicity/Toxicokinetics |
Specific toxicological data for YS-370 is not available. As a P-gp inhibitor, the primary safety concern is the potential for increased toxicity of co-administered chemotherapeutic agents (e.g., paclitaxel) due to their enhanced accumulation in normal tissues (e.g., bone marrow, peripheral nerves). Standard safety assessment would involve a 14-day repeat-dose combination toxicity study in rats (YS-370 + paclitaxel). Key endpoints would include body weight, clinical chemistry, hematology (CBC with differential to monitor for myelosuppression), and histopathological examination of the bone marrow, gastrointestinal tract, and peripheral nerves. An in vitro hERG channel assay would also be performed to assess the risk of QT prolongation.
|
| References | |
| Additional Infomation |
YS-370 is a research-grade chemical and is not approved for clinical use. It is a potent, highly selective, and orally active P-glycoprotein (ABCB1) inhibitor.. It is used as a research tool to study the reversal of multidrug resistance (MDR) in cancer chemotherapy, particularly in combination with drugs like paclitaxel. YS-370 has a unique mechanism of action in that it stimulates the ATPase activity of P-gp, which is distinct from classical inhibitors like verapamil and cyclosporine A. It is for research use only.
|
| Molecular Formula |
C37H35BRN4O3
|
|---|---|
| Molecular Weight |
663.60
|
| Exact Mass |
662.189
|
| CAS # |
2470908-79-1
|
| PubChem CID |
162679251
|
| Appearance |
White to off-white solid powder
|
| LogP |
7.2
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
10
|
| Heavy Atom Count |
45
|
| Complexity |
903
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
N1=C2C(C=C(OCCCN3CCOCC3)C(OC)=C2)=C(C2C3=C(N(CC4=CC=CC=C4Br)C=2C2=CC=CC=C2)C=CC=C3)N=C1
|
| InChi Key |
WSOJDUFWINGDJI-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C37H35BrN4O3/c1-43-33-23-31-29(22-34(33)45-19-9-16-41-17-20-44-21-18-41)36(40-25-39-31)35-28-13-6-8-15-32(28)42(24-27-12-5-7-14-30(27)38)37(35)26-10-3-2-4-11-26/h2-8,10-15,22-23,25H,9,16-21,24H2,1H3
|
| Chemical Name |
4-[3-[4-[1-[(2-bromophenyl)methyl]-2-phenylindol-3-yl]-7-methoxyquinazolin-6-yl]oxypropyl]morpholine
|
| 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: 8.33 mg/mL (12.55 mM)
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5069 mL | 7.5347 mL | 15.0693 mL | |
| 5 mM | 0.3014 mL | 1.5069 mL | 3.0139 mL | |
| 10 mM | 0.1507 mL | 0.7535 mL | 1.5069 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
