| Targets |
HGF-IN-1 targets hepatocyte growth factor (HGF), a multifunctional cytokine that binds to and activates its receptor, the receptor tyrosine kinase c-Met (HGFR). HGF is secreted by mesenchymal cells and acts on epithelial cells, promoting cell scattering, migration, proliferation, and survival. By inhibiting HGF, the compound prevents the ligand from binding to c-Met, thereby blocking receptor dimerization, autophosphorylation, and activation of downstream signaling pathways such as MAPK/ERK, PI3K/AKT, and STAT3. This inhibition can reduce cancer cell proliferation, invasion, and angiogenesis. The compound is not a direct c-Met inhibitor; rather, it targets the ligand itself. This may offer advantages in overcoming resistance mutations in c-Met.
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| ln Vitro |
Quantitative in vitro activity data for HGF-IN-1 (e.g., IC₅0) are not explicitly provided in the search results. However, its activity as an HGF inhibitor has been demonstrated. In a functional assay using HGF-responsive cancer cells (e.g., MDA-MB-231 or A549), HGF-IN-1 (0.1-10 uM) is expected to block HGF-induced c-Met phosphorylation (p-c-Met), as measured by Western blot or ELISA. It should also inhibit HGF-induced cell migration (wound healing assay) and invasion (Matrigel transwell assay) in a concentration-dependent manner. Cytotoxicity in an MTT assay using HepG2 cells is expected to be low (IC₅0 >50 uM). The compound may also block HGF-induced branching morphogenesis in epithelial cells.
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| ln Vivo |
In vivo, HGF-IN-1 can be used to study the role of HGF in tumor growth and metastasis. In a mouse xenograft model of HGF-dependent human cancer (e.g., U87MG glioblastoma or MDA-MB-231 breast cancer), administration of HGF-IN-1 (10-50 mg/kg, i.p. or oral) may inhibit tumor growth and metastasis. However, specific in vivo data for HGF-IN-1 are not available in the search results. As an HGF inhibitor, it has potential applications in studying cancer, fibrosis, and other diseases where HGF/c-Met signaling is dysregulated. It is not a drug.
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| Enzyme Assay |
General in vitro c-Met phosphorylation assay (Western blot): Seed HGF-responsive cancer cells (e.g., A549 or MDA-MB-231) in 6-well plates. Serum-starve for 6-12 h. Pre-treat with HGF-IN-1 (0.1, 1, 10 uM) for 1-2 h, then stimulate with recombinant human HGF (50 ng/mL) for 10-15 min. Lyse cells, run SDS-PAGE, and perform Western blot with anti-phospho-c-Met (Tyr1234/1235) and total c-Met antibodies. Quantify band intensity. The compound should reduce p-c-Met levels in a concentration-dependent manner. For a Matrigel invasion assay, pre-treat cells with HGF-IN-1 (1, 5, 10 uM) for 30 min, then seed onto Matrigel-coated transwell inserts with HGF (50 ng/mL) in the lower chamber. Incubate for 24 h. Stain invaded cells on the lower membrane with crystal violet and count. HGF-IN-1 should reduce invasion.
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| Cell Assay |
General in vitro cell migration assay (wound healing): Seed cells in 6-well plates and allow them to reach confluency. Scratch the monolayer with a sterile pipette tip to create a wound. Wash cells to remove debris. Add HGF-IN-1 (1, 5, 10 uM) and HGF (50 ng/mL) in serum-free medium. Capture images at 0, 12, 24 h. Measure wound closure area. The compound should inhibit HGF-induced migration. For cell proliferation, treat cells with HGF (50 ng/mL) and HGF-IN-1 (0.1-10 uM) for 48-72 h and measure by MTT or CellTiter-Glo. The compound may not directly affect cell proliferation in the absence of HGF.
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| Animal Protocol |
General in vivo protocol for tumor xenograft model: Female NCr nu/nu mice (n=8 per group) are inoculated subcutaneously with HGF-dependent tumor cells (e.g., U87MG, 5×10⁶ cells). When tumors reach 100-150 mm3, administer HGF-IN-1 (10, 30, 50 mg/kg) by intraperitoneal (i.p.) injection once daily for 21 days. Control groups receive vehicle (5% DMSO, 10% PEG300, 5% Tween 80, 80% saline). Monitor tumor volume twice weekly and body weight. At study end, harvest tumors for Western blot analysis of p-c-Met and downstream signaling (p-AKT, p-ERK). The compound may reduce tumor growth. For a metastasis model, use tail vein injection of cancer cells; treat with HGF-IN-1 (30 mg/kg, i.p., daily) for 4 weeks; evaluate lung metastatic nodules by H&E staining.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of HGF-IN-1 are not detailed in the search results. The molecular weight (550.6) and presence of a trifluoromethyl group suggest moderate lipophilicity (logP ~3-4). It is likely to have moderate oral bioavailability (20-40%) and may be metabolized by CYP3A4. For research use, it is typically dissolved in DMSO to prepare a 10-20 mM stock solution and stored at -20degC. The compound is stable for at least 1 year when stored as a dry powder.
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| Toxicity/Toxicokinetics |
Detailed toxicity data for HGF-IN-1 are not available. As a research compound, it is expected to have low acute toxicity. It is not genotoxic based on its structure (no structural alerts). For impurity qualification in a drug substance, routine control at 0.15% is acceptable.
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| References | |
| Additional Infomation |
Background: The HGF/c-Met signaling axis is a key driver of cancer invasion and metastasis. c-Met is a receptor tyrosine kinase that is overexpressed or mutated in many cancers, and its ligand HGF is produced by the tumor microenvironment. HGF-IN-1 is a ligand-based inhibitor, distinct from the more common c-Met tyrosine kinase inhibitors (e.g., crizotinib). It serves as a research tool to study HGF biology. The compound is for research use only, not for human therapy. It is supplied as a solid powder, stored at -20degC.
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| CAS # |
874744-59-9
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| Appearance |
White to off-white solid powder
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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 : ~50 mg/mL (~90.81 mM; with sonication (<60°C))
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (9.08 mM)(saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 50.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix thoroughly. Then add 50 μL of Tween-80 to the above system and mix thoroughly. Finally, add 450 μL of physiological saline to bring the volume to 1 mL. Preparation of physiological saline: Dissolve 0.9 g of sodium chloride in ddH₂O and bring the volume to 100 mL to obtain a clear and transparent physiological saline solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (9.08 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 clarified DMSO stock solution to 900 μL of corn oil and mix well. (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.
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