Cat. No.: HY-187719

NIK-12192

Name: NIK-12192
Brand: MedChemExpress
SKU: HY-187719
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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.

For research use only. We do not sell to patients.

CAS No.: 318262-42-9
Formula: C₂₆H₃₁Cl₂N₃O₂
Molecular Weight:488.45

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Please store the product under the recommended conditions in the Certificate of Analysis.

NIK-12192 Chemical Structure

CAS No.: 318262-42-9

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Biological Activity
- Description
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
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References
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Biological Activity

Description

Cellular Effect

Cell Line	Type	Value	Description	References
HT-29	IC50	1.06 μM	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.	19723111
LoVo	IC50	2.51 μM	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.	19723111
HCT-116	IC50	2.58 μM	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.	19723111
NCI-H460	IC50	2.20 μM	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.	19723111
POVD	IC50	2.53 μM	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.	19723111
OVCAR-3	IC50	2.58 μM	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.	19723111
HL-60	IC50	2.86 μM	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.	19723111

In Vitro

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.

Immunofluorescence^[1]

Cell Line:

human colon carcinoma HT29 cells
Concentration:

1 μM
Incubation Time:

20 min; 120 min
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.

Cell Proliferation Assay^[1]

Cell Line:

human colon carcinoma cells
Concentration:

0.05 and 0.2 μM
Incubation Time:

7 days (long-term); 2 h (short-term)
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.

Apoptosis Analysis^[1]

Cell Line:

human colon carcinoma HT29 cells
Concentration:

5 μM
Incubation Time:

24 h; 48 h; 72 h; 96 h; 120 h
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.

Western Blot Analysis^[2]

Cell Line:

human nonsmall cell lung carcinoma H460 cells
Concentration:

2 μM
Incubation Time:

24 h
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.

Cell Migration Assay ^[2]

Cell Line:

human nonsmall cell lung carcinoma H460 cells
Concentration:

0.5, 1 and 2 μM
Incubation Time:

24 h pretreatment, plus continuous exposure during 5 h migration assay
Result:

Caused a concentration-dependent inhibition of H460 cell migration.
Showed no effect on cell adhesion at tested concentrations.

Cell Invasion Assay^[2]

Cell Line:

human nonsmall cell lung carcinoma H460 cells
Concentration:

0.5, 1 and 2 μM
Incubation Time:

24 h pretreatment, plus continuous exposure during 24 h invasion assay
Result:

Caused a concentration-dependent inhibition of H460 cell invasion.
Showed no effect on cell adhesion at tested concentrations.

Immunofluorescence^[2]

Cell Line:

human nonsmall cell lung carcinoma H460 cells
Concentration:

2 μM
Incubation Time:

24 h
Result:

Induced a shift of αvβ3 integrin from polarized cytoplasmic localization in control cells to more homogeneous diffuse distribution in treated cells.

In Vivo

NIK-12192 (30 mg/kg; p.o.; 5 times per week for 9 weeks) reduces spontaneous lung metastasis and partially inhibits primary tumor growth in female athymic nude CD-1 mice bearing subcutaneously inoculated H460 non-small cell lung cancer xenografts^[2].
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.

Animal Model:

CD-1 (female, 8 to 11 weeks old, s.c. inoculation of H460 ascitic tumor cells)^[2]
Dosage:

30 mg/kg
Administration:

p.o.; daily 5 times/week; 9 weeks
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%.

Animal Model:

CD-1 (female, 8 to 11 weeks old, i.v. injection of H460 ascitic tumor cells)^[2]
Dosage:

30 mg/kg
Administration:

p.o.; daily 5 times/week; 7 weeks
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%.

Animal Model:

CD-1 (female, 8 to 11 weeks old, s.c. inoculation of H460 ascitic tumor cells)^[2]
Dosage:

30 mg/kg
Administration:

p.o.; daily; 2 weeks
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%.

Chemical Information

CAS No. 318262-42-9
Molecular Weight 488.45
Formula C₂₆H₃₁Cl₂N₃O₂
SMILES

O=C(C1=CC(OCC)=C(C2=CC3=CC(Cl)=C(C=C3N2)Cl)C=C1)NC4CC(C)(C)NC(C)(C4)C
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation

Handling Instructions (2659 KB)

References

[1]. Supino R, et al. Biological effects of a new vacuolar-H,-ATPase inhibitor in colon carcinoma cell lines. Annals of the New York Academy of Sciences. 2009 Aug;1171:606-16.

[2]. Supino R, et al. Antimetastatic effect of a small-molecule vacuolar H+-ATPase inhibitor in in vitro and in vivo preclinical studies. The Journal of pharmacology and experimental therapeutics. 2008 Jan;324(1):15-22.

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NIK-12192