| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| 500mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
Axl (IC50 = 10 μM); Axl (Kd = 12 μM)
RU-301 targets the TAM (Tyro3, Axl, Mer) receptor family, a group of receptor tyrosine kinases that are involved in cell survival, proliferation, migration, and immune regulation. RU-301 binds at the interface between the ligand Gas6 and the Ig1 domain of the respective TAM receptors. This binding disrupts receptor dimerization and activation. By blocking Gas6-induced TAM activation, RU-301 inhibits downstream signaling pathways including Akt and ERK activation. |
|---|---|
| ln Vitro |
In H1299 cells, RU-301 (10 μM; 30 minutes) suppresses natural TAM activation [1]. H1299 and MDA-MB-231 cells' ability to migrate is inhibited by RU-301 (10 μM; 24 hours) [1].
In vitro, RU-301 suppresses natural TAM activation in H1299 cells at 10 μM for 30 minutes. It inhibits the migration of H1299 and MDA-MB-231 cells at 10 μM for 24 hours. At 10 μM, RU-301 inhibits Gas6-induced native Axl phosphorylation in H1299 cells, as well as native Tyro3 and MerTK. 5 μM partially blocks Gas6-induced Akt and Erk activation. The compound inhibits the clonal growth of H1299 cells when cultured in the presence of Gas6. |
| ln Vivo |
RU-301 (intraperitoneal injection; 100–300 mg/kg; once daily for 4 days) suppresses the growth of tumors in xenograft animals [1]. In mice with NOD/SCIDγ (4-6 weeks; lung cancer xenograft model), RU-301 (300 mg/kg; i.p.; 3 times weekly) decreases liver fibrosis [1]. in ation [2].
In vivo, RU-301 suppresses the growth of tumors in xenograft animals at doses of 100-300 mg/kg administered intraperitoneally once daily for 4 days. In NOD/SCIDγ mice with lung cancer xenografts, RU-301 at 300 mg/kg administered intraperitoneally three times weekly decreases liver fibrosis. The compound dramatically diminished tumor volume while body weights were not significantly different, demonstrating no notable toxicity but good bioavailability with a half-life of ~7-8 hours. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for RU-301 are not typically performed because the compound targets protein-protein interactions rather than enzyme activity. However, its binding to TAM receptors can be assessed using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) to measure the Kd. Competitive binding assays with labeled ligands can also be used to determine the IC50 for inhibition of Gas6 binding.
|
| Cell Assay |
Cell Viability Assay[1]
Cell Types: H1299, MDA-MB-231 cells Tested Concentrations: 10 μM (for H1299); (10 μM; 14 days) Inhibits the growth of H1299 clone-forming cells under Gas6[1]. 2.5, 5 μM (for MDA-MB-231) Incubation Duration: 30 minutes (pre-incubation) Experimental Results: Inhibition of Gas6-induced native phosphorylation of native Axl. 5 μM partially blocks Gas6-induced Akt and Erk activation in H1299 or MDA-MB-231. At 10 μM, it inhibits not only Gas6-induced native Axl phosphorylation in H1299, but also native Tyro3 and MerTK. Cell migration assay [1] Cell Types: H1299, MDA-MB-231 Cell Tested Concentrations: 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: Strongly inhibited Gas6-induced motility of H1299 lung cancer cell line. Cell viability assay[1] Cell Types: H1299 Cell Tested Concentrations: 10 μM Incubation Duration: 14 days Experimental Results: Clonal growth of H1299 cells was inhibited when cultured in the presence of Gas6. In vitro cellular assays for RU-301 are performed using various cancer cell lines, including H1299 and MDA-MB-231 cells. Cells are treated with varying concentrations of RU-301, and TAM receptor phosphorylation is assessed by Western blotting using phospho-specific antibodies. Cell migration is assessed using transwell migration assays. Cell viability and clonal growth are measured using colony formation assays. These assays confirm the compound's ability to inhibit TAM receptor activation and downstream signaling. |
| Animal Protocol |
Animal/Disease Models: NOD/SCIDγ mice (4-6 week; lung cancer xenograft model)[1].
Doses: 100, 300 mg/kg Route of Administration: intraperitoneal (ip) injection; single daily for 4 days Experimental Results:Dramatically diminished tumor volume while body weights were not Dramatically different. demonstrated no notable toxicity but displayed good bioavailability with a t1/2 life of ~7-8 hrs (hrs (hours)). Animal/Disease Models: WT or Mertk−/− male mice (fed NASH diet for 12 weeks) [2]. Doses: 300 mg/kg Route of Administration: intraperitoneal (ip) injection; 3 times a week for 4 weeks Experimental Results: diminished liver Sirius red staining and collagen gene expression indicated diminished liver fibrosis. In vivo animal experiments for RU-301 are conducted in xenograft mouse models of lung cancer. NOD/SCIDγ mice are implanted with human lung cancer cells and treated with RU-301 via intraperitoneal injection at doses of 100-300 mg/kg. Tumor growth inhibition is monitored, and endpoints include tumor volume, tumor weight, and survival. Liver fibrosis is assessed in NASH models. Pharmacodynamic markers such as TAM phosphorylation in tumor tissues are assessed. The compound demonstrates good bioavailability with a half-life of ~7-8 hours. |
| ADME/Pharmacokinetics |
RU-301 has a molecular weight of 496.47 and is a small-molecule inhibitor. The compound is soluble in DMSO and other organic solvents. Detailed pharmacokinetic parameters have been characterized, showing good bioavailability and a half-life of ~7-8 hours in mice. The compound shows no notable toxicity at effective doses. For in vivo administration, it can be formulated in appropriate vehicles for intraperitoneal injection.
|
| Toxicity/Toxicokinetics |
RU-301 has been evaluated in preclinical studies and has been reported to be well-tolerated at effective doses, with no notable toxicity observed. The compound demonstrates good bioavailability with a half-life of ~7-8 hours. As a pan-TAM inhibitor, RU-301 may have potential effects on immune regulation and cell survival. Standard toxicology studies would be necessary to fully assess its safety profile for clinical development.
|
| References | |
| Additional Infomation |
RU-301 is a novel pan-TAM receptor inhibitor that blocks Gas6-induced TAM activation and tumorigenicity. It targets Axl, Tyro3, and MerTK with a Kd of 12 μM and an IC50 of 10 μM. RU-301 significantly reduces nonalcoholic steatohepatitis (NASH) fibrosis and attenuates ERK activation and TGFβ1 expression. It suppresses tumor growth in xenograft models and has good bioavailability with a half-life of ~7-8 hours. RU-301 is a research compound and is not an approved drug.
|
| Molecular Formula |
C21H19F3N4O4S
|
|---|---|
| Molecular Weight |
480.460173845291
|
| Exact Mass |
480.107
|
| Elemental Analysis |
C, 52.50; H, 3.99; F, 11.86; N, 11.66; O, 13.32; S, 6.67
|
| CAS # |
1110873-99-8
|
| Related CAS # |
1110873-99-8
|
| PubChem CID |
40135492
|
| Appearance |
Light yellow to khaki solid powder
|
| LogP |
5
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
33
|
| Complexity |
666
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
BPHPWPNHNGXNPR-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C21H19F3N4O4S/c1-13-10-15(32-27-13)12-33-19-5-3-2-4-16(19)20(29)26-9-8-25-17-7-6-14(21(22,23)24)11-18(17)28(30)31/h2-7,10-11,25H,8-9,12H2,1H3,(H,26,29)
|
| Chemical Name |
2-[(3-methyl-1,2-oxazol-5-yl)methylsulfanyl]-N-[2-[2-nitro-4-(trifluoromethyl)anilino]ethyl]benzamide
|
| Synonyms |
RU-301; RU 301; RU301
|
| 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: 96~250 mg/mL (199.8~520.3 mM)
Ethanol: ~2.5 mg/mL (~5.2 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.33 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 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 | 2.0813 mL | 10.4067 mL | 20.8134 mL | |
| 5 mM | 0.4163 mL | 2.0813 mL | 4.1627 mL | |
| 10 mM | 0.2081 mL | 1.0407 mL | 2.0813 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
COA
