| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
P-glycoprotein (P-gp, ABCB1) (Ki = 3.2 μM for P-gp ATPase activity inhibition) [1]
|
|---|---|
| ln Vitro |
In vitro, lathyrol has the ability to reverse the effects of MCF-7/ADR breast cancer cell lines [1].
- Lathyrol acts as a modulator of P-gp-dependent multidrug resistance (MDR). It dose-dependently enhanced the cytotoxicity of P-gp substrate chemotherapeutic drugs (doxorubicin, paclitaxel) in P-gp-overexpressing MDR cell lines (KB-V1, A2780/T), reducing their IC50 values by ~3-8 fold compared with drug-alone groups (detected by MTT assay) [1] - Lathyrol (1-10 μM) inhibited P-gp-mediated drug efflux, increasing the intracellular accumulation of P-gp substrates (rhodamine 123, doxorubicin) in KB-V1 cells in a dose-dependent manner (detected by flow cytometry) [1] - Lathyrol (0.1-10 μM) inhibited P-gp ATPase activity in a concentration-dependent manner, with a Ki value of 3.2 μM (detected by ATPase activity assay). It did not alter the protein expression level of P-gp in KB-V1 cells (detected by Western blot) [1] - Lathyrol showed low intrinsic cytotoxicity to parental sensitive cell lines (KB, A2780) and MDR cell lines (KB-V1, A2780/T) at concentrations up to 20 μM (MTT assay) [1] |
| Enzyme Assay |
- P-gp ATPase activity assay: Membrane vesicles containing overexpressed P-gp were suspended in reaction buffer. Lathyrol (0.01-100 μM) was added to the vesicles, followed by the addition of ATP to initiate the reaction. After incubation at 37°C for 30 minutes, the reaction was terminated, and the released inorganic phosphate (Pi) was quantified by a colorimetric method to calculate P-gp ATPase activity inhibition rate and Ki value [1]
|
| Cell Assay |
- MDR reversal assay: P-gp-overexpressing MDR cells (KB-V1, A2780/T) and parental sensitive cells (KB, A2780) were seeded in 96-well plates. Cells were treated with Lathyrol (0.1-20 μM) alone or in combination with chemotherapeutic drugs (doxorubicin/paclitaxel) for 72 hours. MTT reagent was added, and absorbance at 570 nm was measured to calculate cell viability and IC50 values [1]
- Intracellular drug accumulation assay: KB-V1 cells were loaded with P-gp fluorescent substrate (rhodamine 123) and treated with Lathyrol (1-10 μM) for 1 hour. Intracellular fluorescence intensity was detected by flow cytometry to evaluate substrate accumulation [1] - P-gp expression assay: KB-V1 cells were treated with Lathyrol (1-10 μM) for 48 hours. Cells were lysed, and proteins were extracted for Western blot analysis using anti-P-gp antibody. β-actin was used as an internal control to quantify P-gp protein level [1] |
| References | |
| Additional Infomation |
Lathyrol has been reported to be present in plants of the genus Euphorbia lathyris, and relevant data exist. Lathyrol is a natural diterpenoid compound belonging to the lacsilol type, isolated from plants of the genus Euphorbia [1]. Its mechanism of reversing multidrug resistance includes inhibiting P-gp ATPase activity and blocking P-gp-mediated drug efflux without downregulating P-gp protein expression [1]. Lathyrol can serve as a lead compound for developing multidrug resistance modulators; structure-activity relationship (SAR) studies have shown that its C-12, C-13, and C-14 sites are crucial for P-gp regulatory activity [1].
|
| Molecular Formula |
C20H30O4
|
|---|---|
| Molecular Weight |
334.4498
|
| Exact Mass |
334.214
|
| CAS # |
34420-19-4
|
| PubChem CID |
15479845
|
| Appearance |
White to off-white solid powder
|
| Density |
1.2±0.1 g/cm3
|
| Boiling Point |
503.5±50.0 °C at 760 mmHg
|
| Flash Point |
272.4±26.6 °C
|
| Vapour Pressure |
0.0±2.9 mmHg at 25°C
|
| Index of Refraction |
1.566
|
| LogP |
2.69
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
0
|
| Heavy Atom Count |
24
|
| Complexity |
605
|
| Defined Atom Stereocenter Count |
7
|
| SMILES |
C[C@H]1C[C@]2([C@H]([C@H]1O)[C@H](C(=C)CC[C@H]3[C@H](C3(C)C)/C=C(/C2=O)\C)O)O
|
| InChi Key |
SDBITTRHSROXCY-SVSKDHLKSA-N
|
| InChi Code |
InChI=1S/C20H30O4/c1-10-6-7-13-14(19(13,4)5)8-11(2)18(23)20(24)9-12(3)17(22)15(20)16(10)21/h8,12-17,21-22,24H,1,6-7,9H2,2-5H3/b11-8+/t12-,13-,14+,15-,16-,17-,20+/m0/s1
|
| Chemical Name |
(1R,3E,5R,7S,11R,12R,13S,14S)-1,11,13-trihydroxy-3,6,6,14-tetramethyl-10-methylidenetricyclo[10.3.0.05,7]pentadec-3-en-2-one
|
| 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 (~299.00 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.47 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 25.0 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.47 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 | 2.9900 mL | 14.9499 mL | 29.8998 mL | |
| 5 mM | 0.5980 mL | 2.9900 mL | 5.9800 mL | |
| 10 mM | 0.2990 mL | 1.4950 mL | 2.9900 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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