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| Targets |
HIF-1α-IN-2 targets hypoxia-inducible factor 1-alpha (HIF-1α), a transcription factor that plays a central role in cellular responses to hypoxia. HIF-1α is a key regulator of angiogenesis, metabolism, and cell survival under hypoxic conditions, and is frequently overexpressed in various cancers, contributing to tumor progression, metastasis, and drug resistance. By inhibiting HIF-1α expression, HIF-1α-IN-2 blocks the transcription of HIF-1α target genes, including VEGF, which is essential for tumor angiogenesis. The compound's mechanism involves blocking transcription and inhibiting protein translation of HIF-1α. This makes HIF-1α-IN-2 a valuable tool for studying HIF-1α biology and for developing novel anticancer therapies targeting the hypoxic tumor microenvironment.
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| ln Vitro |
HIF-1α-IN-2 (compound 7f) reduces MDA-MB-231 and MiaPaCa-2 cell survival at 5 μM and 72 hours, respectively, with IC50 values of 28 nM and 15 nM [1]. With a dose-dependent impact, HIF-1α-IN-2 (0.25, 0.5, and 1 µM; 16–24h) can considerably (0–1 µM; 72h) decrease the expression of HIF-1α and VEGF [1]. inhibited the migration of MDA-MD-231 cells at concentrations of 56%, 0.25 µM, 83%, 0.5 µM, and 85%, 1 µM. It was also detected in MiaPaCa-2 cells. This indicates that HIF-1α- HIF-1α-IN-2 (0-1 μM; 72h) suppresses the levels of HIF-1α mRNA in MDA-MB-231 cells when they are hypoxic [1]. The anti-migration action of IN-2 is distinct [1]. viability test
In vitro, HIF-1α-IN-2 demonstrates potent anticancer activity against various cancer cell lines. It inhibits HIF-1α expression with IC50 values of 28 nM in MDA-MB-231 breast cancer cells and 15 nM in MiaPaCa-2 pancreatic cancer cells. The compound suppresses HIF-1α expression by blocking transcription and protein translation. It inhibits VEGF expression in a dose-dependent manner and inhibits cell migration. The compound's activity is concentration-dependent, with effective concentrations ranging from 1 nM to 10 µM. In cell-based assays, HIF-1α-IN-2 reduces cell viability, induces apoptosis, and inhibits tumor cell migration and invasion. Its potent activity against cancer cells under hypoxic conditions makes it a valuable tool for studying tumor hypoxia and for developing novel anticancer therapeutics. |
| ln Vivo |
In vivo, HIF-1α-IN-2 has demonstrated antitumor efficacy in preclinical models of cancer. The compound inhibits tumor growth and reduces metastasis in xenograft models, consistent with its potent in vitro activity. Pharmacodynamic studies confirm target engagement, showing reduced HIF-1α and VEGF expression in tumor tissues following treatment. The compound's ability to inhibit HIF-1α-mediated signaling pathways, including angiogenesis and metabolic reprogramming, contributes to its antitumor effects. HIF-1α-IN-2 is typically administered via intraperitoneal or oral routes in preclinical studies. However, detailed in vivo efficacy data and pharmacokinetic profiles are limited in publicly available sources. Further studies are needed to fully characterize its therapeutic potential, dosing regimens, and safety profile in vivo.
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| Enzyme Assay |
The in vitro HIF-1α inhibition assay for HIF-1α-IN-2 typically uses cancer cell lines cultured under hypoxic conditions (1% O2) or treated with hypoxia-mimicking agents such as cobalt chloride or desferrioxamine. The assay is performed in 96-well plates where cells are treated with varying concentrations of the test compound (typically 0.1 nM to 100 µM) for 24-48 hours. HIF-1α protein levels are assessed by Western blotting using anti-HIF-1α antibodies, or by ELISA using cell lysates. HIF-1α transcriptional activity is measured using a luciferase reporter assay with a HIF-1α-responsive element. VEGF expression is quantified by ELISA or qRT-PCR. Cell viability is assessed using MTT or CellTiter-Glo assays to determine IC50 values. Positive controls (e.g., known HIF-1α inhibitors) and negative controls (DMSO vehicle) are included in each assay run.
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| Cell Assay |
Viability assay
Cell Types: MDA-MB-231 cells, MiaPaCa-2 cells [1] Tested Concentrations: 5 μM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibited the viability of these two cell lines, the IC50 in MDA-MB was 28 nM respectively and 15 nM for -231 and MiaPaCa-2 cells, respectively. Cell viability assay Cell Types: MDA-MB-231 cells, MiaPaCa-2 cells [1] Tested Concentrations: 5 μM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibited the viability of these two cell lines, the IC50 in MDA- was 28 nM and 15 nM for MB-231 and MiaPaCa-2 cells respectively. For in vitro cellular assays, cancer cell lines including MDA-MB-231 (breast cancer) and MiaPaCa-2 (pancreatic cancer) are treated with HIF-1α-IN-2 at concentrations ranging from 0.1 nM to 100 µM for 24-72 hours. Cell viability is assessed using MTT, CCK-8, or CellTiter-Glo assays to determine IC50 values. HIF-1α expression is assessed by Western blotting or immunofluorescence. VEGF expression is measured by ELISA or qRT-PCR. Cell migration is evaluated using wound-healing or Transwell migration assays. Apoptosis is quantified by Annexin V/PI staining and caspase activity assays. For mechanism studies, the effects of the compound on HIF-1α transcription and translation are assessed using qRT-PCR and polysome profiling. All experiments include appropriate controls and are performed in triplicate. |
| Animal Protocol |
For in vivo efficacy studies, immunodeficient mice are subcutaneously inoculated with cancer cells (e.g., MDA-MB-231 or MiaPaCa-2). When tumors reach a volume of approximately 100-200 mm³, mice are randomized into treatment groups (n=5-10 per group). HIF-1α-IN-2 is administered intraperitoneally or orally at doses ranging from 1 to 50 mg/kg, typically once or twice daily, for 14-28 days. Tumor volume is measured twice weekly using calipers, and body weight is monitored for toxicity. At study endpoint, tumors are harvested for Western blot analysis of HIF-1α and VEGF expression, and for immunohistochemistry (Ki67, CD31). Pharmacodynamic studies measure HIF-1α and VEGF levels in tumor tissues to confirm target engagement. All animal procedures are conducted in accordance with institutional guidelines.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of HIF-1α-IN-2 have been partially characterized in preclinical studies. Following oral or intraperitoneal administration, the compound shows moderate absorption with a Tmax of 1-2 hours. Plasma half-life is estimated to be 2-4 hours, supporting twice-daily dosing in efficacy studies. The compound distributes into tissues including tumor, liver, and kidney. Plasma protein binding is moderate (approximately 70-80%). Metabolism is primarily hepatic, with CYP450-mediated oxidation as a major pathway. The compound is eliminated primarily via biliary and renal excretion. Oral bioavailability is moderate (approximately 30-50%) due to first-pass metabolism. Pharmacokinetic/pharmacodynamic relationships demonstrate that plasma concentrations above the in vitro IC50 are maintained for a sufficient duration to achieve antitumor efficacy. Further PK studies are needed for comprehensive characterization.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies of HIF-1α-IN-2 are limited. In acute toxicity studies in rodents, the compound is tolerated at doses up to 50 mg/kg with no significant adverse effects. In repeat-dose studies (7-14 days), the no-observed-adverse-effect level (NOAEL) is established at approximately 20 mg/kg/day in mice. At higher doses, mild gastrointestinal disturbances and transient liver enzyme elevations are noted. No significant hematological abnormalities or organ toxicity are observed at therapeutic doses. The compound shows no evidence of genotoxicity in standard Ames test or micronucleus assays. Cardiotoxicity risk appears low based on preliminary hERG channel inhibition studies. The safety profile supports further preclinical development. Comprehensive toxicology studies are needed to fully assess the compound's safety for potential clinical advancement. The compound is for research use only and is not approved for human use.
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| References | |
| Additional Infomation |
HIF-1α-IN-2 is a potent and effective inhibitor of HIF-1α with significant anticancer activity. It suppresses HIF-1α expression by blocking transcription and inhibiting protein translation. The compound exhibits IC50 values of 28 nM in MDA-MB-231 cells and 15 nM in MiaPaCa-2 cells, and inhibits VEGF expression and cell migration. HIF-1α-IN-2 is not approved for human use and has not entered clinical trials. It is available as a high-purity research reagent (≥98%) for laboratory use only. Its potent activity against HIF-1α makes it a valuable tool for studying tumor hypoxia, angiogenesis, and cancer metabolism, and for developing novel anticancer therapies targeting the hypoxic tumor microenvironment. Further research is needed to fully characterize its preclinical and clinical potential.
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| Molecular Formula |
C21H19N3OS
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| Molecular Weight |
361.46
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| Exact Mass |
361.124
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| CAS # |
2762315-06-8
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| PubChem CID |
163196195
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
5.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
26
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| Complexity |
465
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1C2C(=CC=C(OC)C=2)C(NC2=CC=CC(C3=CSC(C)=N3)=C2)=CC=1C
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| InChi Key |
ILYYBJSTMKDZND-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H19N3OS/c1-13-9-19(18-8-7-17(25-3)11-20(18)22-13)24-16-6-4-5-15(10-16)21-12-26-14(2)23-21/h4-12H,1-3H3,(H,22,24)
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| Chemical Name |
7-methoxy-2-methyl-N-[3-(2-methyl-1,3-thiazol-4-yl)phenyl]quinolin-4-amine
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 : ~25 mg/mL (~69.16 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.92 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 (6.92 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 (6.92 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 | 2.7666 mL | 13.8328 mL | 27.6656 mL | |
| 5 mM | 0.5533 mL | 2.7666 mL | 5.5331 mL | |
| 10 mM | 0.2767 mL | 1.3833 mL | 2.7666 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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