| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
GAC0001E5 targets the liver X receptors (LXRα and LXRβ), which are nuclear receptors that regulate cholesterol metabolism, lipid homeostasis, and inflammation. As an inverse agonist, it suppresses the basal transcriptional activity of LXR. Additionally, GAC0001E5 induces degradation of both LXRα and LXRβ proteins, providing a dual mechanism of action that enhances its antiproliferative effects.
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| ln Vitro |
In vitro, GAC0001E5 demonstrates antiproliferative activity against pancreatic cancer cells with IC50 values ranging from 5.4 to 9.1 μM. It also inhibits breast cancer cells (MDA-MB-231) with an IC50 of 7.74 μM. The compound induces LXRα/β protein degradation and inhibits LXR transcriptional activity, leading to suppression of tumor growth and induction of apoptosis. These effects are mediated through the modulation of LXR target genes involved in cell proliferation and survival.
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| ln Vivo |
In vivo, GAC0001E5 has demonstrated antitumor activity in preclinical cancer models. As a dual LXR inverse agonist and degrader, it suppresses tumor growth by inhibiting LXR-mediated transcriptional programs that support cancer cell survival and proliferation. Detailed in vivo efficacy data, including effects on tumor growth in xenograft models, are described in the primary literature. The compound's dual mechanism may provide enhanced efficacy compared to LXR antagonists.
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| Enzyme Assay |
Non-cellular binding assays for GAC0001E5 involve measuring its binding affinity to LXRα and LXRβ using techniques such as fluorescence polarization, scintillation proximity assays, or surface plasmon resonance. The compound's ability to inhibit LXR transcriptional activity can be assessed in cell-free systems using purified LXR proteins and coactivator peptides. Degradation of LXR proteins can be studied using purified protein degradation assays or by monitoring protein stability in the presence of the compound.
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| Cell Assay |
In vitro cellular experiments with GAC0001E5 are conducted in cancer cell lines such as pancreatic (e.g., Panc-1) and breast (e.g., MDA-MB-231) cancer cells. Cells are treated with the compound at various concentrations, and LXR transcriptional activity is measured using luciferase reporter assays. LXRα and LXRβ protein levels are assessed by Western blotting to confirm degradation. Cell viability and proliferation are evaluated using standard assays such as MTT, CellTiter-Glo, or BrdU incorporation assays.
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| Animal Protocol |
In vivo animal studies for GAC0001E5 are performed in murine xenograft models using human pancreatic or breast cancer cell lines. Tumor-bearing mice are treated with the compound via appropriate routes of administration. Tumor growth is monitored over time, and endpoints include tumor volume measurements, survival analysis, and pharmacodynamic assessments of LXR target gene expression and LXR protein levels in tumor tissues. Efficacy is compared to vehicle controls.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of GAC0001E5 are being characterized during preclinical development. The compound's molecular properties would influence its absorption, distribution, metabolism, and excretion. Detailed pharmacokinetic parameters such as half-life, bioavailability, and tissue distribution would be determined in appropriate animal models. Researchers should consult the primary literature and supplier documentation for specific information. Storage conditions should follow the supplier's recommendations.
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| Toxicity/Toxicokinetics |
Toxicity data for GAC0001E5 are generated during preclinical development. As an LXR modulator, potential toxicities may include effects on lipid metabolism and liver function. Comprehensive toxicology studies would assess safety margins and identify target organ toxicities. Researchers should consult the safety data sheet and handle the compound with appropriate laboratory safety precautions for research use only.
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| References | |
| Additional Infomation |
GAC0001E5 is a research compound also known as LXR ligand 1E5. The CAS number is 927969-67-3. It is a small molecule LXR inverse agonist and a potent inhibitor of pancreatic and breast cancer cells. The compound has antiproliferative activity and can be used in cancer research. All products are for research use only and not for human use.
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| Molecular Formula |
C17H12F3N3O
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|---|---|
| Molecular Weight |
331.291893959045
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| Exact Mass |
331.093
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| CAS # |
927969-67-3
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| PubChem CID |
135773837
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| Appearance |
White to off-white solid powder
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| LogP |
3.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
24
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| Complexity |
536
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C(C=C1)C2=CC(=O)NC(=N2)NC3=CC=CC(=C3)C(F)(F)F
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| InChi Key |
NKINUPRRPNHKNN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H12F3N3O/c18-17(19,20)12-7-4-8-13(9-12)21-16-22-14(10-15(24)23-16)11-5-2-1-3-6-11/h1-10H,(H2,21,22,23,24)
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| Chemical Name |
4-phenyl-2-[3-(trifluoromethyl)anilino]-1H-pyrimidin-6-one
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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) |
Typically soluble in DMSO (e.g. 10 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0185 mL | 15.0925 mL | 30.1850 mL | |
| 5 mM | 0.6037 mL | 3.0185 mL | 6.0370 mL | |
| 10 mM | 0.3019 mL | 1.5093 mL | 3.0185 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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