| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
P-glycoprotein[1]
Reversin 121 specifically targets P-glycoprotein (P-gp, also known as ABCB1 or MDR1), an ATP-dependent efflux pump that exports a wide range of xenobiotics, including many anticancer drugs. It binds to the P-gp multidrug transporter with a Kd value of 77 nM and modulates P-gp ATPase activity. By competitively binding to P-gp, Reversin 121 inhibits its efflux function, leading to increased intracellular accumulation of chemotherapeutic agents. |
|---|---|
| ln Vitro |
When used in conjunction with gemcitabine, reversin 121 (12 μg/mL) decreases the percentage of tumor cells that express MDR proteins in Panc1 cells[1]. In paclitaxel-resistant NCI-H460 cells, reversin 121 (5 μM) reverses the resistance against paclitaxel[2]. Proliferation of T cells is inhibited by reversin 121 (10 μM, 48 h)[3].
In vitro, Reversin 121 binds to the P-gp multidrug transporter (MDR1) with a Kd value of 77 nM. It modulates P-glycoprotein ATPase activity in Sf9 insect cell membranes expressing human MDR1 and in plasma membrane vesicles from multidrug-resistant cancer cells. By blocking the function of P-gp, Reversin 121 increases the intracellular accumulation and retention of chemotherapeutic agents, thus restoring sensitivity in resistant cancer cells. Reversin 121 is reported to have little toxic side effects at concentrations effective for reversing MDR. |
| ln Vivo |
Tumor growth and metastasis prevalence are reduced by reversin 121 (2.5 mg/kg with 5-fluorouracil, 35 mg/kg/day, ip)[1].
In vivo, the addition of Reversin 121 to chemotherapy regimens has been shown to significantly reduce the proportion of pancreatic cancer cells expressing MDR proteins, leading to a reduction in tumor size and metastasis in experimental models. By reversing P-gp-mediated multidrug resistance, it enhances the efficacy of co-administered chemotherapeutic agents. However, detailed in vivo efficacy data for this specific compound across multiple tumor models requires further investigation. |
| Enzyme Assay |
The in vitro protocol for assessing P-gp inhibition by Reversin 121 involves a rhodamine-123 accumulation assay. Multidrug-resistant cancer cells (e.g., MCF-7/ADR or Caco-2) are seeded in 96-well plates at 1×10⁴ cells/well. After 24 hours, cells are pre-incubated with Reversin 121 at concentrations ranging from 0.1-50 uM for 30-60 minutes. Rhodamine-123 (a fluorescent P-gp substrate) is then added to a final concentration of 5 ug/mL. After 30-60 minutes of incubation, cells are washed twice with cold PBS, and the intracellular fluorescence is measured using a microplate reader (Ex/Em = 485/528 nm). Non-specific binding is determined using verapamil (10 uM) as a positive control.
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| Cell Assay |
For in vitro cellular chemosensitization assays, multidrug-resistant cancer cells (e.g., MCF-7/ADR or pancreatic cancer cells overexpressing P-gp) are seeded in 96-well plates at 5×103 cells/well. After 24 hours, cells are treated with a combination of Reversin 121 (0.1-50 uM) and varying concentrations of a chemotherapeutic agent (e.g., paclitaxel, doxorubicin, or gemcitabine) for 48-72 hours. Cell viability is assessed using the MTT assay or CellTiter-Glo reagent. The chemosensitization effect is quantified as the fold reversal of resistance, calculated by comparing the IC50 of the chemotherapeutic agent in the presence versus absence of Reversin 121.
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| Animal Protocol |
Animal/Disease Models: Orthotopic pancreatic carcinoma mouse model[1].
Doses: 2.5 mg/ kg, plus 5-fluorouracil, 35 mg/kg/day Route of Administration: intraperitoneal (ip) injection (ip), 5 days a week Experimental Results: diminished in MRP3-positive cells. An in vivo protocol for Reversin 121 uses a xenograft mouse model of human pancreatic cancer resistant to gemcitabine. Female athymic nude mice (6-8 weeks old) are inoculated subcutaneously with gemcitabine-resistant pancreatic cancer cells (e.g., MIA PaCa-2-derived resistant clones). When tumors reach approximately 100 mm3, mice are randomized into groups. Reversin 121 is administered intraperitoneally at a dose of 10-20 mg/kg in 100-200 uL PBS, 30 minutes prior to gemcitabine injection (50 mg/kg, i.p.). Treatment is given daily or every other day for 14-21 days. Tumor volumes are measured with calipers twice weekly. At study termination, tumors are harvested for Western blot analysis of P-gp expression and immunohistochemistry for Ki-67. |
| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for Reversin 121 is not extensively published. As a peptide-based P-gp inhibitor, it is expected to have moderate metabolic stability and is typically administered intraperitoneally or intravenously for in vivo studies due to expected low oral bioavailability. The compound binds to P-gp with high affinity (Kd = 77 nM), but its own absorption, distribution, metabolism, and excretion (ADME) parameters, including T1/2, Cmax, and AUC, have not been characterized in standard databases.
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| Toxicity/Toxicokinetics |
Reversin 121 is reported to have little toxic side effects at concentrations effective for reversing multidrug resistance (MDR). A Material Safety Data Sheet indicates potential hazards: strong acids/alkalis and strong oxidizing/reducing agents may cause decomposition, and under fire conditions, toxic fumes may be emitted. Standard safety precautions should be followed when handling this compound. As a peptide-based inhibitor, it is expected to have low systemic toxicity at therapeutic doses, but comprehensive toxicity studies (e.g., repeat-dose toxicity in rodents) have not been published.
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| References |
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| Additional Infomation |
Reversin 121 is a hydrophobic peptide chemosensitizer that can reverse P-glycoprotein-mediated multidrug resistance.
Reversin 121 is a research-grade chemical and is not approved for clinical use. Its molecular formula is C34H47N3O9 with a molecular weight of 641.75 and a purity of >99%. It is a hydrophobic peptide chemosensitizer that reverses P-gp-mediated multidrug resistance by binding to the P-gp multidrug transporter (Kd = 77 nM) and increasing the ATPase activity of MDR1. Reversin 121 is a valuable tool for cancer research, particularly for overcoming chemoresistance in pancreatic cancer and other malignancies where P-gp overexpression is a key mechanism of drug resistance. |
| Molecular Formula |
C34H47N3O9
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|---|---|
| Molecular Weight |
641.75
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| Exact Mass |
641.331
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| CAS # |
174630-04-7
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| PubChem CID |
9939298
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| Appearance |
Colorless to light yellow ointment
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| LogP |
6.185
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
21
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| Heavy Atom Count |
46
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| Complexity |
977
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| Defined Atom Stereocenter Count |
2
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| SMILES |
O=C(OCC1=CC=CC=C1)NCCCC[C@@H](C(OC(C)(C)C)=O)NC([C@@H](NC(OC(C)(C)C)=O)CC(OCC1=CC=CC=C1)=O)=O
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| InChi Key |
SVNKEDMVAQBLLN-SVBPBHIXSA-N
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| InChi Code |
InChI=1S/C34H47N3O9/c1-33(2,3)45-30(40)26(19-13-14-20-35-31(41)44-23-25-17-11-8-12-18-25)36-29(39)27(37-32(42)46-34(4,5)6)21-28(38)43-22-24-15-9-7-10-16-24/h7-12,15-18,26-27H,13-14,19-23H2,1-6H3,(H,35,41)(H,36,39)(H,37,42)/t26-,27-/m0/s1
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| Chemical Name |
tert-butyl (2S)-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxo-4-phenylmethoxybutanoyl]amino]-6-(phenylmethoxycarbonylamino)hexanoate
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| 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 | 1.5582 mL | 7.7912 mL | 15.5824 mL | |
| 5 mM | 0.3116 mL | 1.5582 mL | 3.1165 mL | |
| 10 mM | 0.1558 mL | 0.7791 mL | 1.5582 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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