A-800141
A-800141 is an orally active, selective, sulfonamide-based MetAP2 inhibitor (IC50=12 nM) that binds reversibly to MetAP2 and interacts with its manganese ions. A-800141 induces the production of N-terminal methionine-unprocessed GAPDH variants, which in turn triggers G1-phase cell cycle arrest, elevates p21 levels, and reduces the levels of phosphorylated Rb and total cyclin A. A-800141 exhibits anti-angiogenic and tumor growth inhibitory effects, and produces synergistic effects when combined with cytotoxic inhibitors or BCL-2 inhibitors. A-800141 has been widely used in scientific research related to B-cell lymphoma, neuroblastoma, prostate cancer, colon cancer, melanoma and other fields.
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- CAS. Nr.: 681245-85-2
- Formel: C24H30N2O4S
- Molecular Weight:442.57
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biologische Aktivität
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Chemical Information
- Reinheit & Dokumentation
- Verweise
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Help & FAQs
Biologische Aktivität
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MetAp1 36 μM (IC50) |
MetAp2 12 nM (IC50) |
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Cell Line
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Type | Value | Description | References |
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| HT-1080 | EC50 |
0.019 μM
Compound: 24a
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Antiproliferative activity against HT1080
Antiproliferative activity against HT1080
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[PMID: 16789740] |
| HT-1080 | EC50 |
0.023 μM
Compound: 24a
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Inhibition of MetAP2-mediated methionine processing in HT1080 cells
Inhibition of MetAP2-mediated methionine processing in HT1080 cells
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[PMID: 16789740] |
| HT-1080 | EC50 |
0.26 μM
Compound: 24a
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Antiproliferative activity against HT1080 in presence of 40 mg/ml human serum albumin
Antiproliferative activity against HT1080 in presence of 40 mg/ml human serum albumin
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[PMID: 16789740] |
A-800141 potently inhibits the proliferation of HMVEC, HT1080, HCT116, A549, NCI-H460 and B16F10 cells, and also induces quiescent G1 cell cycle arrest and alters the expression of cell cycle markers in HUVEC[1].
A-800141 (0.0004-3 μM; 48 h) inhibits N-terminal processing of GAPDH in bEND3 cells, with an EC50 of 20 nM in regular medium and 100 nM in medium containing 40 mg/mL HSA[1].
A-800141 (100 nM; 3 d) induces G1 cell cycle arrest in HUVECs and regulates cell cycle regulatory proteins including p21, p53, phosphorylated Rb and cyclin A[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Human microvascular endothelial cells (HMVEC), human fibrosarcoma cells (HT1080), human colon carcinoma cells (HCT116), human lung carcinoma cells (A549), human lung large cell carcinoma cells (NCI-H460), murine melanoma cells (B16F10), human umbilical vein endothelial cells (HUVEC)
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Concentration:10 nM, 100 nM, 100 μM
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Incubation Time:24 hours, 3 days
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Result:Exhibited potent antiproliferative activity across all tested cell lines, with IC50 values of 10 nM (HMVEC), 26 nM (HT1080), 18 nM (HCT116), 25 nM (A549), 11 nM (NCI-H460), and 11 nM (B16F10).
Induced cytostatic G1 phase cell cycle arrest without apoptosis.
Initiated G1 arrest in HUVEC at 10 nM, with a significant increase in G1-phase cells (54% vs. 39% in controls) observed at 100 nM after 24 hours of treatment.
Produced a similar G1 arrest profile in HUVEC at 100 μM with 3 days incubation.
Elevated p21 and modestly increased p53 levels, reduced phosphorylated Rb, and decreased total cyclin A levels in HUVEC.
A-800141 (150 mg/kg per day; p.o.; twice daily; days 14-end) does not significantly inhibit tumor growth as a single agent in a male SCID beige mouse SuDHL4 B cell lymphoma xenograft model, but produces significant tumor inhibition when combined with etoposide[1].
A-800141 (50-200 mg/kg per day; p.o.; twice daily; days 1-14) produces 85% tumor growth inhibition and significant GAPDH processing blockade in both WBCs and tumor tissue in a C57BL/6 mouse B16F10 melanoma model, with efficacy correlating to the degree of MetAP2 inhibition measured by GAPDH variants[1].
A-800141 (75-150 mg/kg; p.o.; daily) achieves 70% growth inhibition of CHP-134 neuroblastoma xenografts in SCID mice with good tolerability[3].
A-800141 (100-150 mg/kg; p.o.; twice daily) causes significant growth delay of PC-3 prostate carcinoma xenografts in SCID mice[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:SCID mice with Neuroblastoma (female; CHP-134 human neuroblastoma cells inoculated into flanks, tumors staged to 200 mm3)[1]
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Dosage:150 mg/kg per day; 75 mg/kg per day
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Administration:p.o.; twice daily
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Result:Produced 70% tumor growth inhibition at 150 mg/kg per day.
Caused significant tumor growth inhibition relative to vehicle control at both doses.
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Animal Model:C57BL/6 mice with Melanoma (B16F10 murine melanoma cells inoculated into flanks)[1]
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Dosage:200 mg/kg per day; 100 mg/kg per day; 50 mg/kg per day
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Administration:p.o.; twice daily; days 1-14
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Result:Produced 85% tumor growth inhibition at 200 mg/kg per day.
Blocked GAPDH processing significantly (40% of total GAPDH as unprocessed variant in WBCs and tumor tissues) at 200 mg/kg per day.
Caused significant tumor growth inhibition relative to vehicle control at all doses, with efficacy tracking the degree of methionine retention in GAPDH.
Chemical Information
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CAS. Nr. 681245-85-2
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Molecular Weight 442.57
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Formel C24H30N2O4S
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SMILES
O=C(C1=C2CCCCC2=CC=C1NS(=O)(C3=CC=CC=C3/C=C\CN(CC)CC)=O)O
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Reinheit & Dokumentation
Verweise
[1]. Wang J, et al. Correlation of tumor growth suppression and methionine aminopetidase-2 activity blockade using an orally active inhibitor. Proc Natl Acad Sci U S A. 2008;105(6):1838-1843. [Content Brief]
[2]. Yin SQ, et al. The development of MetAP-2 inhibitors in cancer treatment. Curr Med Chem. 2012;19(7):1021-1035. [Content Brief]
[3]. Mauriz JL, et al. Methionine aminopeptidases as potential targets for treatment of gastrointestinal cancers and other tumours. Curr Drug Targets. 2010;11(11):1439-1457. [Content Brief]
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
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