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^[1][2][3].

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.

A-800141 (75-150 mg/kg per day; p.o.; twice daily) produces 70% tumor growth inhibition in a female SCID mouse CHP-134 neuroblastoma xenograft model^[1].
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.

442.57

C₂₄H₃₀N₂O₄S

681245-85-2

O=C(C1=C2CCCCC2=CC=C1NS(=O)(C3=CC=CC=C3/C=C\CN(CC)CC)=O)O

Room temperature in continental US; may vary elsewhere.

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

• [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.