| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
RAS (KRAS, HRAS, NRAS) and RAS-RAF interaction.
|
|---|---|
| ln Vitro |
RAS/RAS-RAF-IN-1 (Compound 89) possesses an EC50 of 0.5 μM-5.0 μM for disrupting BRAF-GTP-KRAS-G12C and an IC50 of 1.0 μM-10 μM for inhibiting pERK in H358 cells [1].
RAS/RAS-RAF-IN-1 inhibits the RAS-RAF protein-protein interaction; it has a KD of 5.0-15 uM for cyclophilin A (CYPA) binding affinity; it demonstrates an EC50 of 0.5-5.0 uM for disrupting BRAF-GTP-KRAS-G12C and an IC50 of 1.0-10 uM for inhibiting pERK in H358 cells (KRAS mutant lung cancer cells). |
| ln Vivo |
RAS/RAS-RAF-IN-1 displays anti-tumor effects in vivo; specific studies (e.g., mouse xenograft models of KRAS-mutant cancers) are likely to show tumor growth inhibition, but quantitative data are not fully detailed in open sources.
|
| Enzyme Assay |
CYPA binding affinity is measured by surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC); recombinant cyclophilin A protein is immobilized, and RAS/RAS-RAF-IN-1 is flowed over at various concentrations; binding affinity (KD) is calculated from the binding kinetics.
|
| Cell Assay |
RAS-RAF interaction disruption and pERK inhibition are assessed in H358 human lung cancer cells (KRAS G12C mutant); cells are cultured in RPMI-1640 medium with 10% FBS; after treatment with RAS/RAS-RAF-IN-1 (0.5-10 uM), the RAS-RAF interaction is measured by co-immunoprecipitation (Co-IP) or proximity ligation assay (PLA); pERK levels are measured by Western blot using anti-pERK (Thr202/Tyr204) antibodies; EC50 and IC50 values are calculated.
|
| Animal Protocol |
Mouse xenograft models of KRAS-mutant cancer (e.g., H358 or MIA PaCa-2 cells) are typically used; when tumors reach a certain size, RAS/RAS-RAF-IN-1 is administered via intraperitoneal or oral route daily; endpoints include tumor volume measurement, body weight, and molecular analysis (pERK, proliferation markers) in excised tumors; no specific published data are available.
|
| ADME/Pharmacokinetics |
PK properties not fully detailed; as a small-molecule inhibitor, RAS/RAS-RAF-IN-1 is expected to have moderate to good permeability and bioavailability; however, specific parameters (half-life, clearance, oral bioavailability) are not available in open sources; further ADME studies are required.
|
| Toxicity/Toxicokinetics |
Toxicology profile not fully characterized; as an experimental compound, no formal toxicity studies have been published; potential toxicity would be assessed in preclinical safety studies (acute, repeat-dose, genotoxicity, cardiovascular safety) before clinical advancement; specific data are lacking.
|
| References | |
| Additional Infomation |
RAS/RAS-RAF-IN-1 is a research-use only tool compound for studying RAS biology and the RAS-RAF interaction as a therapeutic target in oncology; it is not approved for clinical use; no clinical trials have been registered; it is of interest for targeting KRAS-mutant cancers, especially those with limited response to direct KRAS G12C inhibitors, by disrupting upstream or downstream signaling nodes in the MAPK pathway; its binding to CYPA suggests a novel mechanism of action beyond direct kinase inhibition.
|
| Molecular Formula |
C45H57N7O7
|
|---|---|
| Molecular Weight |
807.98
|
| Exact Mass |
807.431
|
| CAS # |
2447039-81-6
|
| PubChem CID |
162642485
|
| Appearance |
White to light yellow solid powder
|
| LogP |
5.2
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
59
|
| Complexity |
1660
|
| Defined Atom Stereocenter Count |
4
|
| SMILES |
C(C1=CN2CC(COC([C@]3([H])CCCN(C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C([C@H]4CCN(C(=O)C=C)C4)=O)CC4C=C(O)C=C(C=4)C4=CC=C1C2=C4)N3)=O)(C)C)(C)(C)C#N
|
| InChi Key |
RCXSKUOUWMZVFF-NXCZKTMTSA-N
|
| InChi Code |
InChI=1S/C45H57N7O7/c1-9-38(54)50-16-14-30(22-50)41(56)49(8)39(27(2)3)40(55)47-36-19-28-17-31(20-32(53)18-28)29-12-13-33-34(45(6,7)24-46)23-51(37(33)21-29)25-44(4,5)26-59-43(58)35-11-10-15-52(48-35)42(36)57/h9,12-13,17-18,20-21,23,27,30,35-36,39,48,53H,1,10-11,14-16,19,22,25-26H2,2-8H3,(H,47,55)/t30-,35-,36-,39-/m0/s1
|
| Chemical Name |
(3S)-N-[(2S)-1-[[(8S,14S)-22-(2-cyanopropan-2-yl)-4-hydroxy-18,18-dimethyl-9,15-dioxo-16-oxa-10,20,28-triazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),2,4,6(29),21,23(27),24-heptaen-8-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methyl-1-prop-2-enoylpyrrolidine-3-carboxamide
|
| 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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 : ~200 mg/mL (~247.53 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 6 mg/mL (7.43 mM) in 10% DMSO + 90% (20% SBE-β-CD in 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 60.0 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: ≥ 5 mg/mL (6.19 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 50.0 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 | 1.2377 mL | 6.1883 mL | 12.3765 mL | |
| 5 mM | 0.2475 mL | 1.2377 mL | 2.4753 mL | |
| 10 mM | 0.1238 mL | 0.6188 mL | 1.2377 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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