| Size | Price | Stock | Qty |
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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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| Other Sizes |
| Targets |
KRas G12D-GppNHp (Kd <20 μM)
Pan-RAS (all RAS isoforms including KRAS, NRAS, and HRAS). Ras-IN-3144 disrupts the interaction of Ras proteins with their effectors, thereby inhibiting downstream RAS signaling pathways. By targeting multiple RAS isoforms, the compound has the potential to overcome resistance mechanisms that arise from isoform switching or compensatory signaling. |
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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].
In vitro, Ras-IN-3144 inhibits RAS signaling pathways in cancer cells. The compound disrupts the interaction between Ras proteins and their downstream effectors, leading to inhibition of proliferation and induction of apoptosis in RAS-mutant cancer cell lines. Its pan-RAS activity distinguishes it from isoform-selective inhibitors, offering broader therapeutic potential against tumors with various RAS mutations. |
| 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].
In vivo, Ras-IN-3144 prevents the growth of RAS mutant mouse cancer xenografts. The compound demonstrates anti-tumor activity in preclinical models of RAS-driven cancers, including those with KRAS, NRAS, or HRAS mutations. Its ability to disrupt Ras-effector interactions in vivo results in tumor growth inhibition and improved survival in treated animals. These findings support the potential of Ras-IN-3144 as a therapeutic agent for RAS-mutant cancers. |
| Enzyme Assay |
Cell-free binding assays for Ras-IN-3144 typically involve surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) to measure direct binding to purified Ras proteins (KRAS, NRAS, HRAS). Competition assays with fluorescently labeled effectors (e.g., Raf RBD) are used to assess the compound's ability to disrupt Ras-effector interactions. The compound is incubated with Ras protein and the labeled effector at varying concentrations, and the displacement of the effector is measured. IC50 values are calculated from dose-response curves.
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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].
Cellular assays for Ras-IN-3144 are performed using cancer cell lines harboring RAS mutations (e.g., KRAS-mutant HCT116, SW480, or A549 cells). Cells are seeded in 96-well plates and treated with Ras-IN-3144 at concentrations ranging from 0.01-100 μM for 24-72 hours. Cell viability is measured using MTT, CCK-8, or CellTiter-Glo assays. Downstream signaling inhibition is assessed by Western blot analysis of phosphorylated ERK, AKT, and other RAS pathway components. Cell cycle analysis and apoptosis assays are performed by flow cytometry. Combination studies with other targeted agents can be performed to assess synergistic effects. |
| 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].
In vivo efficacy studies are conducted in immunodeficient mice bearing subcutaneous xenografts of RAS-mutant human cancer cell lines. Ras-IN-3144 is administered via oral gavage or intraperitoneal injection at doses typically ranging from 10-100 mg/kg, daily or on a scheduled regimen. Tumor volume is measured every 2-3 days using calipers. At study termination, tumors are excised, weighed, and processed for immunohistochemistry or Western blot analysis to assess RAS pathway inhibition and pharmacodynamic markers. Pharmacokinetic-pharmacodynamic (PK-PD) relationships are established by correlating drug exposure with target inhibition and anti-tumor efficacy. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Ras-IN-3144 are consistent with small molecule inhibitors. As a pan-RAS inhibitor, the compound is expected to have reasonable oral bioavailability and sufficient plasma exposure for in vivo efficacy. Tissue distribution is expected to include significant tumor penetration due to its small molecule nature. Detailed PK parameters (Cmax, Tmax, AUC, t1/2, clearance, volume of distribution) are determined in preclinical species. Metabolic stability and protein binding are assessed using standard in vitro assays.
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| Toxicity/Toxicokinetics |
Toxicological data for Ras-IN-3144 are limited to preclinical research studies. As a RAS pathway inhibitor, potential toxicities may include effects on normal tissues that depend on RAS signaling for homeostasis. Standard toxicology studies (acute, subchronic, and chronic) in rodents and non-human primates are required for clinical development. At research-grade doses used in xenograft studies, the compound is generally well-tolerated. Comprehensive safety pharmacology studies would be needed for IND-enabling toxicology.
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| References | |
| Additional Infomation |
Ras-IN-3144 is a research compound for studying RAS biology and validating pan-RAS inhibition as a therapeutic strategy. It is not an approved drug and has not entered clinical trials. The compound is available from chemical suppliers for research purposes only. Its pan-RAS activity makes it a valuable tool for investigating the role of RAS signaling in cancer and for developing new therapeutic approaches to RAS-driven tumors. The compound should be stored at -20°C and handled according to standard laboratory safety protocols.
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| Molecular Formula |
C36H41CL2F3N6O2
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|---|---|
| Molecular Weight |
717.650956869125
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| Exact Mass |
716.262
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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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| PubChem CID |
102004330
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| Appearance |
White to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
809.7±65.0 °C at 760 mmHg
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| Flash Point |
443.5±34.3 °C
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| Vapour Pressure |
0.0±2.9 mmHg at 25°C
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| Index of Refraction |
1.631
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| LogP |
5.28
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
49
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| Complexity |
1040
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C1(N)CCNCC1)NCCCN2C3=CC=C(CN4CCN(CC5=C(Cl)C=CC=C5Cl)CC4)C=C3C(C6=CC=C(OC(F)(F)F)C=C6)=C2
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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) |
|---|---|
| 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.
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