| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| Other Sizes |
|
Metarrestin (ML-246; ML246) is a novel and potent RNA polymerase (Pol) I transcription inhibitor that can disrupt the nucleolar structure by interacting with the translation elongation factor eEF1A2. Metarrestin is a first-in-class perinucleolar compartment inhibitor with anticancer activity and favorable PK profiles.
| ln Vitro |
Metarrestin (ML246) kills the perinuclear area of PC3M-GFP-PTB cells with an IC50 of 0.39 μM[2]. In several human skeletal lineages, metarrestin (1 μM; 24 h) lowers the nuclear compartment infection rate. Metarrestin Effects: PC3M and PANC1 cell proliferation is efficiently inhibited by metarrestin (0.6 μM; 24 hours); normal fibroblasts (GM02153) are not affected by this drug [2]. PC3M and PANC1 cell proliferation is significantly inhibited by metarrestin (1 μM; 24 hours) [2]. ] had no discernible effect on the levels of the Pol I large subunits RPA194 and UBF in the HeLa, PC3M, and PANC1 cell lines. In cells, metarrestin significantly lowers 5'ETS RNA [2].
|
|---|---|
| ln Vivo |
At 25 mg/kg, metorrestin (ML246; 5–25 mg/kg; intraperitoneally; once daily; for six weeks) demonstrated a decreased burden on the lungs and liver (p <0.01) [2]. meal; 70 ppm; 10 mg/kg) increases the NSG PANC1 pancreatic cancer metastatic model's longevity [2]. The growth of truck carcinoma metastases (PC3M) and the PDX mouse model of metastatic breast cancer is inhibited by metorrestin (5, 25 mg/kg; i.p.; extra 4 weeks) [2]. The half-life of metorrestin (5 and 25 mg/kg; IP) is 4.6 to 5.5 hours [2].
|
| Animal Protocol |
Animal/Disease Models: NOD/IL2 gamma (null) PANC1 mouse primary tumor tissue [2]
Doses: 5 and 25 mg/kg Route of Administration: IP; one time/day; for six weeks Experimental Results: At the 25 mg/kg dose, Both liver (p <0.01) and lung metastatic burden were diminished. demonstrated a Dramatically diminished prevalence of perinucleolar compartments in metastatic and primary tumor tissue. Animal/Disease Models: Female balb/c (Bagg ALBino) mouse [2] Doses: 5 and 25 mg/kg (pharmacokinetic/PK/PK analysis) Route of Administration: IP Experimental Results: Good in vivo exposure, distribution and tolerance, with a half-life of 4.6 to 5.5 hrs (hrs (hours)) . |
| References |
|
| Additional Infomation |
Metarrestin is an orally available small molecule inhibitor of perinucleolar compartment (PNC), with potential antineoplastic activities. Although the exact mechanisms(s) through which this agent exerts its effects have yet to be fully elucidated, upon oral administration, metarrestin disrupts the structure of PNC and inhibits RNA polymerase (Pol) I transcription. This leads to the reduction in the prevalence of PNC in cancer cells and decrease in tumor growth and spread. PNC is a subnuclear structure and a phenotypic marker of metastatic cancer cells. A high PNC prevalence has been associated with disease progression and poor patient outcomes.
|
| Molecular Formula |
C31H30N4O
|
|---|---|
| Molecular Weight |
474.60
|
| Exact Mass |
474.24
|
| Elemental Analysis |
C, 78.45; H, 6.37; N, 11.81; O, 3.37
|
| CAS # |
1443414-10-5
|
| PubChem CID |
50985821
|
| Appearance |
White to off-white solid powder
|
| LogP |
5.6
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
36
|
| Complexity |
759
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
WSMXAUJFLWRPNT-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C31H30N4O/c32-30-28-27(23-12-6-2-7-13-23)29(24-14-8-3-9-15-24)34(20-22-10-4-1-5-11-22)31(28)33-21-35(30)25-16-18-26(36)19-17-25/h1-15,21,25-26,32,36H,16-20H2
|
| Chemical Name |
4-(7-benzyl-4-imino-5,6-diphenylpyrrolo[2,3-d]pyrimidin-3-yl)cyclohexan-1-ol
|
| Synonyms |
ML246 ML-246
|
| 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 : ~31.25 mg/mL (~65.84 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (4.38 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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 | 2.1070 mL | 10.5352 mL | 21.0704 mL | |
| 5 mM | 0.4214 mL | 2.1070 mL | 4.2141 mL | |
| 10 mM | 0.2107 mL | 1.0535 mL | 2.1070 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
