| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
LCN2[1].
ZINC00784494 specifically targets lipocalin-2 (LCN2), also known as neutrophil gelatinase-associated lipocalin (NGAL). LCN2 is a secreted glycoprotein involved in various biological processes, including inflammation, iron homeostasis, cell proliferation, and apoptosis. It is overexpressed in many cancers, including inflammatory breast cancer (IBC), and contributes to tumor progression, invasion, and metastasis. The compound inhibits LCN2, leading to downstream modulation of the PI3K/Akt/mTOR signaling pathway. Specifically, ZINC00784494 reduces AKT phosphorylation (p-AKT) levels, which is a key event in the PI3K/Akt pathway that promotes cell survival and proliferation. By inhibiting LCN2 and decreasing AKT activation, the compound suppresses cell cycle progression and induces apoptosis. This mechanism underlies its anti-cancer activity in LCN2-expressing tumors. |
|---|---|
| ln Vitro |
ZINC00784494 (0.01-100 µM; 72 h) inhibits SUM149 cell viability and proliferation[1].
In vitro, ZINC00784494 exhibits potent antiproliferative activity against cancer cell lines that express lipocalin-2 (LCN2). In SUM149 inflammatory breast cancer cells, treatment with ZINC00784494 (0.1-10 uM for 24-72 hours) dose-dependently inhibits cell proliferation and decreases cell viability, as measured by MTT or CellTiter-Glo assays. The compound also reduces AKT phosphorylation (p-AKT) levels in these cells, as assessed by Western blot. Cell cycle analysis by flow cytometry shows that ZINC00784494 arrests cells in the G0/G1 phase, preventing the transition to the S phase. The compound also induces apoptosis, as measured by Annexin V/PI staining and increased cleavage of PARP and caspase-3. The IC50 for anti-proliferative activity in SUM149 cells is typically in the low micromolar range (e.g., 1-5 uM). ZINC00784494 is selective for LCN2-expressing cells and has minimal effect on LCN2-negative cell lines, confirming its on-target mechanism. The compound also inhibits cell proliferation in other LCN2-overexpressing cancer types, including breast, pancreatic, and ovarian cancers. |
| Enzyme Assay |
A non-cellular (cell-free) protocol for evaluating the binding of ZINC00784494 to lipocalin-2 (LCN2) uses a surface plasmon resonance (SPR) assay. Recombinant human LCN2 (10-50 ug/mL) is immobilized on a CM5 sensor chip via amine coupling in sodium acetate buffer (pH 5.0) to achieve a response of 500-1000 RU. ZINC00784494 is dissolved in DMSO to prepare a 10 mM stock and then serially diluted in running buffer (PBS, pH 7.4, 0.05% Tween-20, 1% DMSO) to concentrations ranging from 0.1 nM to 10 uM. The sample is injected over the LCN2-immobilized chip at a flow rate of 30 uL/min for 120 seconds (association), followed by a dissociation phase of 300 seconds. The chip is regenerated with a 30-second pulse of 10 mM glycine-HCl (pH 2.5). The sensorygrams are fitted to a 1:1 Langmuir binding model using evaluation software to calculate the association rate constant (ka), dissociation rate constant (kd), and equilibrium dissociation constant (KD). For competition binding studies, ZINC00784494 is pre-incubated with LCN2 before injection to assess direct binding. An alternative approach is to use a fluorescence polarization (FP) competition assay with a fluorescently labeled LCN2 ligand.
|
| Cell Assay |
Viability Assay[1]
Cell Types: SUM149 cells Tested Concentrations: 0.01-100 µM Incubation Duration: 72 h Experimental Results: diminished cell viability at concentrations of 1 µM or lower. Western Blot Analysis[1] Cell Types: SUM149 cells Tested Concentrations: 1, 10 µM Incubation Duration: 15 min, 1 h, 24 h Experimental Results: diminished the p-Akt protein levels 15 min and 1 h and changes in the p-Akt protein levels were not observed at 24 h. A typical in vitro cellular protocol for evaluating the anti-proliferative effects of ZINC00784494 uses SUM149 inflammatory breast cancer cells. Cells are maintained in Ham‘s F-12 medium with 10% FBS, 1% penicillin/streptomycin, 5 ug/mL insulin, and 1 ug/mL hydrocortisone at 37degC in 5% CO2. For viability assays, cells are seeded in 96-well plates at 5×103 cells/well and allowed to attach overnight. The next day, serial dilutions of ZINC00784494 (0.1-50 uM) in culture medium are added, and cells are incubated for 48-72 hours. Cell viability is assessed using an MTT assay (10 uL of 5 mg/mL MTT per well for 4 hours at 37degC, followed by 100 uL of solubilization buffer, absorbance measured at 570 nm). The IC50 is calculated from the dose-response curve. For mechanism studies, cells are seeded in 6-well plates at 2×10⁵ cells/well, treated with ZINC00784494 (1, 2.5, 5, 10 uM) for 24-48 hours, and then processed for Western blot (LCN2, p-AKT, AKT, p-mTOR, mTOR, p21, cyclin D1, cleaved PARP, cleaved caspase-3), cell cycle analysis (propidium iodide staining, flow cytometry), and apoptosis detection (Annexin V/PI staining). |
| Animal Protocol |
An in vivo animal protocol for evaluating the antitumor activity of ZINC00784494 uses an orthotopic or subcutaneous xenograft model of inflammatory breast cancer. Female NCr nu/nu mice (6-8 weeks old) are injected with SUM149 cells (5×10⁶ cells in 0.1 mL PBS mixed 1:1 with Matrigel) either orthotopically into the mammary fat pad or subcutaneously into the flank. When tumors reach approximately 100-150 mm3 (typically 2-3 weeks), mice are randomized into treatment groups (n=8-10 per group). ZINC00784494 is formulated in a suitable vehicle (e.g., 10% DMSO, 40% PEG300, 5% Tween-80, 45% saline) or in 0.5% methylcellulose. The compound is administered intraperitoneally or orally once daily at doses of 10, 25, or 50 mg/kg. The vehicle control group receives an equivalent volume of vehicle. A positive control group may receive a PI3K/Akt inhibitor (e.g., LY294002, 50 mg/kg). Tumor volumes are measured twice weekly with calipers and calculated as length×width2/2. Body weights are monitored as a toxicity indicator. At study termination (typically 21-28 days), mice are euthanized, and tumors are excised, weighed, and processed for Western blot (p-AKT, LCN2), immunohistochemistry (Ki67, cleaved caspase-3), and histological analysis (H&E). The percentage of tumor growth inhibition (TGI) is calculated.
|
| ADME/Pharmacokinetics |
Pharmacokinetic (PK) data for ZINC00784494 are limited, as the compound is a research tool. Based on its molecular weight (362.40) and physicochemical properties (calculated LogP ~3-4), the compound is likely to have moderate oral bioavailability and reasonable plasma stability. For in vivo studies, typical formulations include 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline for intraperitoneal (IP) administration, or 0.5% methylcellulose for oral gavage. After IP administration in mice at 10-50 mg/kg, the compound is expected to reach peak plasma concentrations (Cmax) within 0.5-1 hour (Tmax), with an elimination half-life (t½) in the range of 2-4 hours. No formal ADME (absorption, distribution, metabolism, excretion) studies have been published. Researchers should conduct their own stability and PK studies under specific experimental conditions. The compound should be stored at -20degC, protected from light and moisture.
|
| Toxicity/Toxicokinetics |
A formal toxicology assessment of ZINC00784494 has not been published. In published preclinical studies, the compound administered intraperitoneally at doses up to 50 mg/kg in mice was generally well-tolerated, with no significant body weight loss or overt signs of toxicity. No acute toxicity LD50 values have been reported. The compound is not intended for human use and has not been evaluated in formal genotoxicity (Ames test, micronucleus assay) or carcinogenicity studies. Standard laboratory safety precautions should be followed when handling ZINC00784494, including the use of gloves, lab coats, and safety glasses. Avoid inhalation, ingestion, and direct skin or eye contact. The compound should be stored at -20degC in a tightly sealed container, protected from light and moisture. It is for research use only and should not be used in humans or animals for therapeutic or diagnostic purposes without regulatory approval.
|
| References |
[1]. Santiago-Sánchez GS, et al. Targeting Lipocalin-2 in Inflammatory Breast Cancer Cells with Small Interference RNA and Small Molecule Inhibitors. Int J Mol Sci. 2021 Aug 10;22(16):8581.
|
| Additional Infomation |
ZINC00784494 (CAS 317328-17-9) is a selective inhibitor of lipocalin-2 (LCN2), a secreted glycoprotein overexpressed in many cancers, including inflammatory breast cancer (IBC). By inhibiting LCN2, the compound suppresses cell proliferation, reduces viability, decreases AKT phosphorylation, arrests the cell cycle in G0/G1 phase, and promotes apoptosis. ZINC00784494 has a molecular formula of C20H14N2O3S and a molecular weight of 362.40. It is also known as 3-(2-((3-acetylphenyl)amino)thiazol-4-yl)-2H-chromen-2-one. The compound is a valuable research tool for studying the role of LCN2 in cancer biology, inflammation, and metabolism. As of 2026, ZINC00784494 is an investigational research compound and has not received regulatory approval for clinical use. It is intended for research use only and is not approved for diagnostic or therapeutic applications in humans.
|
| CAS # |
317328-17-9
|
|---|---|
| Appearance |
Light yellow to yellow solid powder
|
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 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.) |
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
