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2mg |
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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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Ras-IN-3144 is a novel and potent pan-RAS inhibitor which disrupts the interaction of Ras proteins and their effectors, also inhibits RAS signaling pathways in cancer cells and prevents the growth of RAS mutant mouse cancer xenografts.
Targets |
KRas G12D-GppNHp (Kd <20 μM)
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ln Vitro |
KRasG12D-GppNHp is bound by Pan-RAS-IN-1 with less than 20 μM of affinity. When Pan-RAS-IN-1 attaches to Ras protein, it becomes deadly to cells whose expression of Ras protein is partially reliant on them. Dependency on mutant isoforms throughout a concentration range of five times is correlated with the effectiveness of IN-1. Pan-RAS-IN-1 is cytostatic at certain concentrations, which may be related to pan-RAS inhibition. In primary T-cell acute leukemia (T-ALL) cells, RAS-IN-1 was assessed. After 5 μM treatment, it was found that mutant, selectively deadly NRAS cells only remained 20%–40% viable [1].
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ln Vivo |
Tumor growth occurred after 15 days of pan-RAS-IN-1 therapy. Transcripts treated with pan-RAS-IN-1 showed lower tumor pERK levels than transcripts treated with vehicle. It was also possible to see increased antagonistic caspase-3 regulation, indicating that pan-RAS-IN-1 can activate caspase in this paradigm [1].
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Cell Assay |
Trypsinized, counted, and 1,000 cells/well seeded into 384-well plates are the procedures used for 384-well cancer cell viability assays. After 16 hours, 384-well polypropylene plates with an 8- or 16-point dilution series are used to array pan-RAS-IN-1 (from 10 mM stocks in DMSO). The assay plates are filled with compound solutions at a 1:5 dilution. A 10% final concentration of Alamar blue is reached after 48 hours by adding a 50% solution. Fluorescence intensity at 535 and 590 nm is measured after 6 hours of incubation[1].
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Animal Protocol |
Mice: Pan-RAS-IN-1 orally at 180 mg/kg (12 mg/mL, 10% DMSO, pH 4), orally administered vehicle, or administered in combination with intraperitoneal and intravenous injections at 30 mg/kg (4 mg/mL, 5% DMSO in HBSS at pH 4). Ten oral doses of pan-RAS-IN-1 or vehicle, or six intraperitoneal injections and four intravenous injections, are administered to the mice over a period of 14 days. Every two days, a tumor's size is computed using an electronic caliper[1].
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References |
[1]. Welsch ME, et al. Multivalent Small-Molecule Pan-RAS Inhibitors. Cell. 2017 Feb 23;168(5):878-889.e29
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Molecular Formula |
C36H41CL2F3N6O2
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Molecular Weight |
717.650956869125
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Exact Mass |
716.26
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Elemental Analysis |
C, 60.25; H, 5.76; Cl, 9.88; F, 7.94; N, 11.71; O, 4.46
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CAS # |
1835283-94-7
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Related CAS # |
1835283-94-7
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Appearance |
Solid powder
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SMILES |
C1CNCCC1(C(=O)NCCCN2C=C(C3=C2C=CC(=C3)CN4CCN(CC4)CC5=C(C=CC=C5Cl)Cl)C6=CC=C(C=C6)OC(F)(F)F)N
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InChi Key |
GMDFJPPJWWJNKF-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C36H41Cl2F3N6O2/c37-31-3-1-4-32(38)30(31)23-46-19-17-45(18-20-46)22-25-5-10-33-28(21-25)29(26-6-8-27(9-7-26)49-36(39,40)41)24-47(33)16-2-13-44-34(48)35(42)11-14-43-15-12-35/h1,3-10,21,24,43H,2,11-20,22-23,42H2,(H,44,48)
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Chemical Name |
4-amino-N-[3-[5-[[4-[(2,6-dichlorophenyl)methyl]piperazin-1-yl]methyl]-3-[4-(trifluoromethoxy)phenyl]indol-1-yl]propyl]piperidine-4-carboxamide
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Synonyms |
Ras IN-3144; Ras-IN-3144; Ras-IN 3144; RasIN3144; pan-RAS inhibitor-3144
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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) |
DMSO: ~6 mg/mL (~8.4 mM)
Ethanol: ~6 mg/mL (~8.4 mM) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.48 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 (3.48 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 (3.48 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 | 1.3934 mL | 6.9672 mL | 13.9344 mL | |
5 mM | 0.2787 mL | 1.3934 mL | 2.7869 mL | |
10 mM | 0.1393 mL | 0.6967 mL | 1.3934 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.