NIK-12192
NIK-12192 is an orally active inhibitor of vacuolar H+-ATPase. NIK-12192 reduces intracellular pH, decreases lysosomal volume and acidity, and alters the intracellular localization of V-ATPase by inhibiting proton pumps. NIK-12192 induces αvβ5 integrin polarization, cytoskeletal disruption, cell detachment, anoikis-mediated delayed apoptosis and necrosis, a delayed reduction in mitochondrial membrane potential, and lysosomal/phagosomal accumulation. NIK-12192 inhibits tumor cell migration, invasion, and three-dimensional spheroid growth, and enhances the activity of Topotecan (HY-13768). NIK-12192 suppresses spontaneous lung metastasis in vivo. NIK-12192 is used in research related to colon cancer, ovarian cancer, lung cancer, breast cancer, renal cancer, prostate cancer, acute myeloid leukemia, and melanoma.
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研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- CAS 番号: 318262-42-9
- 分子式: C26H31Cl2N3O2
- 分子量:488.45
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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生物活性
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化学情報
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生物活性
製品説明
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| HT-29 | IC50 |
1.06 μM
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Antiproliferative activity against human colon carcinoma HT29 cells assessed by measuring protein content incubated for 72 hrs by sulforhodamine B assay.
Antiproliferative activity against human colon carcinoma HT29 cells assessed by measuring protein content incubated for 72 hrs by sulforhodamine B assay.
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19723111 |
| LoVo | IC50 |
2.51 μM
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Antiproliferative activity against human colon carcinoma LoVo cells assessed by measuring protein content incubated for 72 hrs by sulforhodamine B assay.
Antiproliferative activity against human colon carcinoma LoVo cells assessed by measuring protein content incubated for 72 hrs by sulforhodamine B assay.
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19723111 |
| HCT-116 | IC50 |
2.58 μM
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Antiproliferative activity against human colon carcinoma HCT116 cells assessed by measuring protein content incubated for 72 hrs by sulforhodamine B assay.
Antiproliferative activity against human colon carcinoma HCT116 cells assessed by measuring protein content incubated for 72 hrs by sulforhodamine B assay.
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19723111 |
| NCI-H460 | IC50 |
2.20 μM
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Antiproliferative activity against human large-cell lung carcinoma H460 cells assessed by measuring protein content incubated for 72 hrs by sulforhodamine B assay.
Antiproliferative activity against human large-cell lung carcinoma H460 cells assessed by measuring protein content incubated for 72 hrs by sulforhodamine B assay.
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19723111 |
| POVD | IC50 |
2.53 μM
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Antiproliferative activity against human small-cell lung carcinoma POVD cells assessed by measuring metabolic activity incubated for 72 hrs by MTT assay.
Antiproliferative activity against human small-cell lung carcinoma POVD cells assessed by measuring metabolic activity incubated for 72 hrs by MTT assay.
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19723111 |
| OVCAR-3 | IC50 |
2.58 μM
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Antiproliferative activity against human ovarian carcinoma OVCAR-3 cells assessed by measuring protein content incubated for 72 hrs by sulforhodamine B assay.
Antiproliferative activity against human ovarian carcinoma OVCAR-3 cells assessed by measuring protein content incubated for 72 hrs by sulforhodamine B assay.
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19723111 |
| HL-60 | IC50 |
2.86 μM
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Antiproliferative activity against human acute myelocytic leukemia HL60 cells assessed by measuring protein content incubated for 72 hrs by sulforhodamine B assay.
Antiproliferative activity against human acute myelocytic leukemia HL60 cells assessed by measuring protein content incubated for 72 hrs by sulforhodamine B assay.
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19723111 |
体外実験
NIK-12192 (5 μM; 48-96 h) reduces the volume and/or acidity of lysosomes in the human colon cancer cell line HT29 in a time-dependent manner[1].
NIK-12192 (1 μM; 16 h) induces the accumulation of lysosomes and phagosomes (but not autophagosomes) in human colon cancer HT29 cells, indicating impaired organelle fusion[1].
NIK-12192 (1 μM; 20-120 min) localizes predominantly in the cytoplasm of human colon cancer HT29 cells, and its distribution pattern shifts from perinuclear granular enrichment to diffuse cytoplasmic localization over time[1].
NIK-12192 potently inhibits the proliferation of human colon cancer cell lines at 72 h (IC50 = 1.06-2.58 μM), and its activity varies across other human tumor cell lines[1].
NIK-12192 (5 μM; 24-72 h) induces progressive detachment of human colon cancer HT29 cells from the matrix. The floating cells remain viable for up to 48 h and retain partial re-adhesion capacity[1].
NIK-12192 (0.05-0.2 μM; 2 h-7 days) inhibits colony formation in human colon cancer cells in a time-dependent manner[1].
NIK-12192 (0.1-1 μM; 3-4 days) inhibits the colony growth of human colon cancer cells without inducing cytostatic effects[1].
NIK-12192 (5 μM; 24-96 h) does not alter the expression level of ανβ5 integrin, but induces the polarization of ανβ5 integrin on the plasma membrane of the human colon cancer cell line HT29[1].
NIK-12192 (2 μM; 24 h) reduces the intracellular pH of H460 cells from approximately 7.2 to approximately 6.2[2].
NIK-12192 (2 μM; 24 h) does not alter the expression of vacuolar H+-ATPase, but induces a shift in its localization from a punctate pattern to a diffuse cytoplasmic distribution in H460 cells[2].
NIK-12192 (0.5-2 μM) inhibits the migration of H460 cells in a concentration-dependent manner without affecting cell adhesion[2].
NIK-12192 (0.5-2 μM; 24 h pretreatment, plus continuous exposure during the 24 h invasion assay) inhibits the invasion of H460 cells in a concentration-dependent manner without affecting cell adhesion[2].
NIK-12192 (0.5 μM; 48 h) reduces the wound healing capacity of H460 cell monolayers[2].
NIK-12192 (2 μM; 24 h) induces the transition of αvβ3 integrin from a polarized distribution to a uniform cytoplasmic distribution in H460 cells[2].
NIK-12192 (2 μM; 24 h) disrupts the cytoskeletal structures of actin and tubulin in H460 cells, including actin filament fragmentation, disappearance of pseudopodia, and disorganization of tubulin filament architecture[2].
NIK-12192 (0.5-2 μM; 24-72 h) inhibits the three-dimensional growth of H460 cell spheroids in a concentration-dependent manner[2].
NIK-12192 (5 μM; 24-120 h) induces delayed apoptosis (apparent after 72 h) and significant necrosis in human colon cancer HT29 cells[1].
NIK-12192 (5 μM; 24-96 h) induces a delayed reduction in the mitochondrial membrane potential of human colon cancer HT29 cells, an effect that first appears at 72 h of treatment[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:human colon carcinoma HT29 cells
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Concentration:1 μM
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Incubation Time:20 min; 120 min
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Result:Showed predominantly perinuclear localization, forming a narrow fluorescence ring and very intense granules often with polar localization after 20 min.
Decreased overall emission signal, with diffuse fluorescence distributed throughout the cytoplasm after 120 min.
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Cell Line:human colon carcinoma cells
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Concentration:0.05 and 0.2 μM
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Incubation Time:7 days (long-term); 2 h (short-term)
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Result:Reduced colony formation to 52% of control levels with long-term treatment of 0.05 μM.
Reduced colony formation to 34% of control levels with long-term treatment of 0.2 μM.
Reduced colony formation to 93% of control levels with short-term treatment of 0.05 μM.
Reduced colony formation to 66% of control levels with short-term treatment of 0.2 μM.
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Cell Line:human colon carcinoma HT29 cells
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Concentration:5 μM
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Incubation Time:24 h; 48 h; 72 h; 96 h; 120 h
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Result:Induced signs of early apoptosis only after 72 h of treatment.
Induced late apoptosis at longer treatment times.
Induced a high extent of necrotic cell death detected via PI permeability.
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Cell Line:human nonsmall cell lung carcinoma H460 cells
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Concentration:2 μM
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Incubation Time:24 h
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Result:Showed no change in vacuolar H+-ATPase expression relative to untreated control cells.
Revealed vacuolar H+-ATPase shifted from cytoplasmic spots in control cells to more homogeneously and diffusely distributed in the cytoplasm of treated cells.
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Cell Line:human nonsmall cell lung carcinoma H460 cells
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Concentration:0.5, 1 and 2 μM
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Incubation Time:24 h pretreatment, plus continuous exposure during 5 h migration assay
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Result:Caused a concentration-dependent inhibition of H460 cell migration.
Showed no effect on cell adhesion at tested concentrations.
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Cell Line:human nonsmall cell lung carcinoma H460 cells
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Concentration:0.5, 1 and 2 μM
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Incubation Time:24 h pretreatment, plus continuous exposure during 24 h invasion assay
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Result:Caused a concentration-dependent inhibition of H460 cell invasion.
Showed no effect on cell adhesion at tested concentrations.
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Cell Line:human nonsmall cell lung carcinoma H460 cells
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Concentration:2 μM
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Incubation Time:24 h
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Result:Induced a shift of αvβ3 integrin from polarized cytoplasmic localization in control cells to more homogeneous diffuse distribution in treated cells.
体内実験
NIK-12192 (30 mg/kg; p.o.; 5 times per week for 7 weeks) shows no inhibitory effect on experimental lung metastasis in female athymic nude CD-1 mice intravenously injected with H460 non-small cell lung cancer cells[2].
NIK-12192 (30 mg/kg; oral administration; once daily; for 2 weeks) causes a slight reduction in tumor microvessel density in female athymic nude CD-1 mice inoculated with subcutaneous H460 non-small cell lung cancer xenografts[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:CD-1 (female, 8 to 11 weeks old, s.c. inoculation of H460 ascitic tumor cells)[2]
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Dosage:30 mg/kg
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Administration:p.o.; daily 5 times/week; 9 weeks
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Result:Reduced mean number of macroscopic lung metastases to 15, representing a 42% inhibition compared to control mice.
Partially inhibited growth of primary s.c. tumors.
Caused no lethal toxicity or body weight loss greater than 5%.
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Animal Model:CD-1 (female, 8 to 11 weeks old, i.v. injection of H460 ascitic tumor cells)[2]
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Dosage:30 mg/kg
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Administration:p.o.; daily 5 times/week; 7 weeks
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Result:Showed no relevant difference in metastatic burden between treated and control mice; all treated mice developed a large metastatic burden similar to controls.
Caused no lethal toxicity or body weight loss greater than 5%.
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Animal Model:CD-1 (female, 8 to 11 weeks old, s.c. inoculation of H460 ascitic tumor cells)[2]
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Dosage:30 mg/kg
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Administration:p.o.; daily; 2 weeks
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Result:Marginally reduced tumor angiogenesis; inhibited microvessel density by 30% compared to control tumors, with the reduction not statistically significant.
Caused no lethal toxicity or body weight loss greater than 5%.
化学情報
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CAS 番号 318262-42-9
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分子量 488.45
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分子式 C26H31Cl2N3O2
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SMILES
O=C(C1=CC(OCC)=C(C2=CC3=CC(Cl)=C(C=C3N2)Cl)C=C1)NC4CC(C)(C)NC(C)(C4)C
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
NIK-12192 関連分類
HY-187719 関連分類
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