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Purity: ≥98%
| Targets |
Etalocib selectively binds to and blocks the leukotriene B4 receptor (LTB4R, also known as BLT1 or P2Y7), thereby inhibiting downstream signaling pathways. Additionally, it directly inhibits 5'-lipoxygenase, a key enzyme in the leukotriene synthesis pathway. This dual mechanism of action allows etalocib to effectively block neutrophil activation and subsequent inflammation.
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| ln Vitro |
The LTB4-induced overexpression of CD11b is inhibited in a concentration-dependent manner by etalocib (LY293111) [1]. Etalocib (LY293111) is a highly effective and specific inhibitor of human neutrophil activity that can be used in vitro [2]. Human pancreatic cancer cells undergo apoptosis and are inhibited from proliferating when exposed to etabacib (LY293111, 250 and 500 nM, 24-72 hours) [3].
Etalocib potently inhibits the specific binding of [³H]LTB4 to its receptor with a Ki of 25 nM. It inhibits LTB4-induced calcium mobilization with an IC₅₀ of 20 nM and LTB4-induced chemotaxis of human neutrophils with an IC₅₀ of 6.3 nM. The compound also demonstrates concentration-dependent inhibition of LTB4-induced CD11b upregulation. In human pancreatic cancer cell lines, etalocib inhibits growth at concentrations of 250-1,000 nM. |
| ln Vivo |
When given intravenously (ED50=14 µg/kg) or orally (ED50=0.4 mg/kg), etalocib (LY293111) produces dose-related inhibition of acute leukotriene B4-induced airway obstruction [2]. Within an hour, A23187-induced pulmonary inflammatory changes can be inhibited by etalocib (LY293111, 10 mg/kg) [2]. In athymic mice, the growth of human pancreatic cancer xenografts is inhibited by etabacib (LY293111, 250 mg/kg/day, oral) [3].
Etalocib has demonstrated in vivo efficacy by inhibiting the growth of subcutaneous xenografts of human pancreatic cancer cells (MiaPaCa-2 and AsPC-1) in athymic mice at a dose of 250 mg/kg/day. This treatment induced apoptosis and S-phase arrest in the tumors. As an orally active compound, it is suitable for convenient administration in animal models to study its antitumor and anti-inflammatory effects. |
| Enzyme Assay |
Non-cellular assays for etalocib involve competitive radioligand binding displacement studies using isolated human neutrophils or membrane preparations expressing the LTB4 receptor (BLT1). These preparations are incubated with [³H]LTB4 and varying concentrations of etalocib. Following incubation and filtration to separate bound from free radioligand, the radioactivity is measured by scintillation counting. IC₅₀ or Ki values for receptor binding are determined from displacement curves.
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| Cell Assay |
Cell proliferation assay [3]
Cell Types: MiaPaCa-2 and AsPC-1 human pancreatic cancer cells. [3] Tested Concentrations: 500 nM. Incubation Duration: 24, 48 and 72 hrs (hours). Experimental Results: Concentration-dependent and time-dependent inhibition of thymidine incorporation in MiaPaCa-2 and AsPC-1 human pancreatic cancer cells. Apoptosis analysis [3] Cell Types: MiaPaCa-2 and AsPC-1 human pancreatic cancer cells. Tested Concentrations: 250 and 500 nM. Incubation Duration: 24 hrs (hours). Experimental Results: Apoptosis of human pancreatic cancer cells was induced. In vitro cellular assays for etalocib involve treating human neutrophils or cancer cell lines with the compound and measuring various functional endpoints. For neutrophils, LTB4-induced calcium mobilization is measured using fluorescent calcium indicators, chemotaxis is assessed using Boyden chamber assays, and CD11b upregulation is quantified by flow cytometry. For cancer cells (e.g., MiaPaCa-2, AsPC-1), cell proliferation is measured using MTT or CellTiter-Glo® assays after 24-72 hours of treatment with 250-1,000 nM etalocib. |
| Animal Protocol |
Animal/Disease Models: guinea pig[2].
Doses: 1-10 mg/kg. Doses: Take once orally. Experimental Results: A single 1 mg/kg oral dose administered 8 hrs (hrs (hours)) before leukotriene B4 challenge inhibited the increase in isolated lung gas volume by 76.7±7.1% (n=4, P<0.002) and 28.6±20.3% (n= 4, P<0.002). NS) given 24 hrs (hrs (hours)) before challenge. A23187 had no effect on lung air retention 1 hour or 2 hrs (hrs (hours)) after challenge (10 mg/kg). However, at 4 hrs (hrs (hours)), the pulmonary air retention response was Dramatically lower than in vehicle-treated controls and not different from sham. The 10 mg/kg dose inhibited A23187-induced lung inflammatory changes within 1 hour but had no effect at 2 or 4 hrs (hrs (hours)) post-challenge. In vivo animal experiments with etalocib are conducted in athymic nude mice bearing subcutaneous xenografts of human pancreatic cancer cell lines (e.g., MiaPaCa-2, AsPC-1). Tumor-bearing mice are treated with etalocib via oral gavage at a dose of 250 mg/kg/day. Tumor growth inhibition is monitored by caliper measurements. At study termination, tumors are collected for histopathological analysis, assessment of apoptosis (e.g., TUNEL assay), and cell cycle analysis (e.g., flow cytometry for S-phase arrest). |
| ADME/Pharmacokinetics |
Etalocib has a molecular weight of 436.54 and a molecular formula of C₂₇H₂₉FO₄. It is a solid powder with a purity of ≥98%. The compound is soluble in DMSO and is typically stored at -20°C. As an orally active compound, etalocib is absorbed after oral administration. Detailed pharmacokinetic parameters such as half-life, Cₘₐₓ, and bioavailability are best characterized in the context of specific preclinical studies.
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| Toxicity/Toxicokinetics |
Toxicity data for etalocib are primarily derived from preclinical studies. In animal models, the compound has been administered at doses up to 250 mg/kg/day. Standard toxicological endpoints would have been assessed in safety pharmacology studies, but detailed toxicity profiles are not widely published in general reference sources. As with any investigational compound, standard laboratory safety precautions should be followed when handling etalocib.
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| References |
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| Additional Infomation |
LY293111 is an aromatic ether. Etalocib has been used in clinical trials to investigate the treatment of pancreatic cancer, carcinoma, non-small cell lung cancer, and unspecified types of adult solid tumors (protocol-specific). Etalocib is a second-generation selective leukotriene B4 receptor (LTB4R) antagonist with potential antitumor activity. Although the exact mechanism of action of LY293111 is not fully elucidated, the drug selectively binds to and blocks LTB4R, thereby inhibiting downstream signaling pathways. Studies have shown that LY293111 can induce apoptosis and inhibit the proliferation of LTB4R-expressing cells, such as pancreatic cancer cells.
Etalocib (LY293111; VML295) is a dual inhibitor of the lipoxygenase pathway, acting as both an LTB4 receptor antagonist and a 5'-lipoxygenase inhibitor. It has been investigated for its anti-inflammatory and antineoplastic properties, with a focus on pancreatic cancer. The compound's oral bioavailability and potent in vitro and in vivo activity made it a candidate for further development. |
| Molecular Formula |
C33H32FNAO6
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|---|---|
| Molecular Weight |
566.59
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| Exact Mass |
544.226
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| CAS # |
161172-51-6
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| Related CAS # |
161172-51-6;
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| PubChem CID |
177941
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
656.8±55.0 °C at 760 mmHg
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| Flash Point |
351.0±31.5 °C
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| Vapour Pressure |
0.0±2.1 mmHg at 25°C
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| Index of Refraction |
1.594
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| LogP |
7.61
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
40
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| Complexity |
743
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
GKDIMGQSBSDJNC-UHFFFAOYSA-M
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| InChi Code |
InChI=1S/C33H33FO6.Na/c1-3-9-25-29(12-7-13-30(25)40-31-11-6-5-10-26(31)33(36)37)38-18-8-19-39-32-21-28(35)27(20-22(32)4-2)23-14-16-24(34)17-15-23/h5-7,10-17,20-21,35H,3-4,8-9,18-19H2,1-2H3,(H,36,37)/q+1/p-1
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| Chemical Name |
sodium 2-(3-(3-((5-ethyl-4'-fluoro-2-hydroxy-[1,1'-biphenyl]-4-yl)oxy)propoxy)-2-propylphenoxy)benzoate
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| Synonyms |
VML295 VML-295 VML 295 LY293111 LY-293111 LY 293111 PDSP1001237 PDSP2001221 Etalocib
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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 : ~100 mg/mL (~183.62 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (4.59 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 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.59 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 25.0 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 | 1.7649 mL | 8.8247 mL | 17.6494 mL | |
| 5 mM | 0.3530 mL | 1.7649 mL | 3.5299 mL | |
| 10 mM | 0.1765 mL | 0.8825 mL | 1.7649 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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