| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg | |||
| Other Sizes |
| Targets |
TrkC (IC50 = 3 nM); TrkB (IC50 = 4 nM); TrkA (IC50 = 6 nM)
Methylnissolin targets the PDGF-BB-induced cell proliferation pathway. It inhibits PDGF-BB-induced phosphorylation of extracellular signal-regulated kinase (ERK). By inhibiting this pathway, it prevents PDGF-BB-induced cell proliferation. It may also target JAK/STAT signaling pathways. |
|---|---|
| ln Vitro |
PF-06273340 is an exceptionally strong pan-Trk inhibitor that possesses a superior LipE profile. Through a series of in vitro safety assays, PF-06273340 is profiled and found to have little cytotoxicity in either HepG2 or THLE cell lines (IC50 > 300 μM or > 42 μM, respectively). With the exception of COX-1 (IC50 = 2.7 μM), dopamine transporter assays (Ki = 5.2 μM), and PDEs 4D, 5A, 7B, 8B, and 11 (54−89% inhibition at 10 μM), all IC50/Ki values in this broad panel were >10 μM. PF-06273340 is screened against 309 kinases in the Invitrogen wide kinase panel. All of the kinases, with the exception of MUSK (IC50 53 nM), FLT-3 (IC50 395 nM), IRAK1 (IC50 2.5 μM), MKK (90% @ 1 μM), and DDR1 (60% @ 1 μM), were inhibited by less than 40% when tested at 1 μM[1].
In vitro, Methylnissolin inhibits PDGF-BB-induced cell proliferation with an IC50 of 10 μM. It inhibits PDGF-BB-induced phosphorylation of ERK. These activities suggest potential applications in diseases characterized by excessive cell proliferation, such as cancer and fibrosis. |
| ln Vivo |
In rats, decreases in white blood cell count are observed from 150 mg/kg/day. Increases in food intake and body weight gain are seen at doses greater than 250 mg/kg; these effects may be explained by central inhibition of TrkB, agonists of which are known to be anorexigenic in rodents. Microscopic observations reveal adaptive alterations in the liver, which are correlated with elevated liver weight (≥250 mg/kg) and elevated cholesterol (1000 mg/kg). PF-06273340 is generally well tolerated up to 1000 mg/kg/day, with an IC50 of roughly 400×TrkA for unbound Cavg plasma exposure[1].
In vivo activity data for Methylnissolin are limited. Its in vitro inhibition of PDGF-BB-induced proliferation suggests potential in vivo activity in models of fibrosis, atherosclerosis, or cancer. Further in vivo studies are needed to confirm its therapeutic potential. |
| Enzyme Assay |
In vitro kinase assays for Methylnissolin are conducted to assess inhibition of PDGF-BB-induced ERK phosphorylation. Cells are stimulated with PDGF-BB in the presence or absence of the compound. ERK phosphorylation is measured by Western blotting using phospho-specific antibodies.
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| Cell Assay |
Cellular assays for Methylnissolin are performed using PDGF-BB-responsive cells, such as vascular smooth muscle cells or fibroblasts. Cells are treated with compound concentrations ranging from 0.1 to 100 µM in the presence of PDGF-BB. Cell proliferation is assessed using BrdU incorporation, MTT, or cell counting assays.
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| Animal Protocol |
Male SD rats
0.25, 2.5 and 25 mg/kg oral administration In vivo animal studies for Methylnissolin would typically utilize rodent models of restenosis, fibrosis, or cancer. The compound is administered orally or intraperitoneally. Endpoints include lesion size, fibrotic area, or tumor growth. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Methylnissolin are not well characterized. The compound has a molecular weight of 300.31. It is a lipophilic isoflavonoid and is expected to have good membrane permeability. Standard PK studies in rodents would be required to determine half-life, bioavailability, and tissue distribution.
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| Toxicity/Toxicokinetics |
Toxicological data for Methylnissolin are limited. As a natural product-derived compound, it may have a moderate safety profile. No significant acute toxicity has been reported. Standard toxicity screening would involve acute and repeated-dose studies in rodents.
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| References | |
| Additional Infomation |
Pterostilbene is a type of stigmacanoid compound. It has been reported that stigmacanoid exists in Dalbergia odorifera, and relevant data is available for reference.
Methylnissolin (Astrapterocarpan) is a naturally occurring isoflavonoid from Astragalus membranaceus that inhibits PDGF-BB-induced cell proliferation (IC50 = 10 μM) and ERK phosphorylation. It is not clinically approved and is used as a research tool for studying PDGF signaling and cell proliferation. |
| Molecular Formula |
C17H16O5
|
|---|---|
| Molecular Weight |
300.3059
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| Exact Mass |
300.099
|
| CAS # |
73340-41-7
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| Related CAS # |
73340-41-7
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| PubChem CID |
14077830
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| Appearance |
White to off-white solid
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
428.9±45.0 °C at 760 mmHg
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| Flash Point |
213.2±28.7 °C
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| Vapour Pressure |
0.0±1.1 mmHg at 25°C
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| Index of Refraction |
1.612
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| LogP |
2.45
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
22
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| Complexity |
403
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| Defined Atom Stereocenter Count |
2
|
| SMILES |
O1C2C(=C(C([H])=C([H])C=2[C@@]2([H])C([H])([H])OC3C([H])=C(C([H])=C([H])C=3[C@@]12[H])O[H])OC([H])([H])[H])OC([H])([H])[H]
|
| InChi Key |
UOVGCLXUTLXAEC-WFASDCNBSA-N
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| InChi Code |
InChI=1S/C17H16O5/c1-19-13-6-5-10-12-8-21-14-7-9(18)3-4-11(14)15(12)22-16(10)17(13)20-2/h3-7,12,15,18H,8H2,1-2H3/t12-,15-/m0/s1
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| Chemical Name |
(6aR,11aR)-9,10-dimethoxy-6a,11a-dihydro-6H-[1]benzofuro[3,2-c]chromen-3-ol
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| Synonyms |
Methylnissolin; Astrapterocarpan
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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: 50~95 mg/mL (166.5~198 mM)
Ethanol: ~1 mg/mL (~2.1 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.32 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 (8.32 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (8.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3299 mL | 16.6495 mL | 33.2989 mL | |
| 5 mM | 0.6660 mL | 3.3299 mL | 6.6598 mL | |
| 10 mM | 0.3330 mL | 1.6649 mL | 3.3299 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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