Development of sulfonamide compounds as potent methionine aminopeptidase type II inhibitors with antiproliferative properties.

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Kawai M, BaMaung NY, Fidanze SD, Erickson SA, Tedrow JS, Sanders WJ, Vasudevan A, Park C, Hutchins C, Comess KM, Kalvin D, Wang J, Zhang Q, Lou P, Tucker-Garcia L, Bouska J, Bell RL, Lesniewski R, Henkin J, Sheppard GS

Development of sulfonamide compounds as potent methionine aminopeptidase type II inhibitors with antiproliferative properties.

Bioorg Med Chem Lett. 2006 Jul 1;16(13):3574-7. Epub 2006 May 2.

PubMed ID
16632353 [ View in PubMed
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Abstract

We have screened molecules for inhibition of MetAP2 as a novel approach toward antiangiogenesis and anticancer therapy using affinity selection/mass spectrometry (ASMS) employing MetAP2 loaded with Mn(2+) as the active site metal. After a series of anthranilic acid sulfonamides with micromolar affinities was identified, chemistry efforts were initiated. The micromolar hits were quickly improved to potent nanomolar inhibitors by chemical modifications guided by insights from X-ray crystallography.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
2-[(PHENYLSULFONYL)AMINO]-5,6,7,8-TETRAHYDRONAPHTHALENE-1-CARBOXYLIC ACIDMethionine aminopeptidase 2IC 50 (nM)97.422Details
5-BROMO-2-{[(4-CHLOROPHENYL)SULFONYL]AMINO}BENZOIC ACIDMethionine aminopeptidase 2IC 50 (nM)91007.422Details
5-METHYL-2-[(PHENYLSULFONYL)AMINO]BENZOIC ACIDMethionine aminopeptidase 2IC 50 (nM)10007.422Details