Development of Non-peptidic Farnesyltransferase Inhibitors based on the Ca<sub>1</sub>a<sub>2</sub>of Ras-CaaX

Lee, Hee Yoon; Chun, Tae-Gyu; Choi, Ho-Jin; Sohn, Jae Hak; Kwon, Byoung‐Mog

doi:10.5012/bkcs.2009.30.2.291

Cited by 4 publications

(1 citation statement)

References 14 publications

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“…9-Aminophenanthrene proves to be an important structural scaffold frequently found in natural products, medicinal chemistry, and functional materials . Furthermore, 9-aminophenanthrene derivatives represent important synthons widely used in organic reactions due to the presence of easily accessible amino groups and other active sites .…”

Section: Introductionmentioning

confidence: 99%

Cascade Reaction of Arylboronic Acids and 2′-Cyano-biaryl-2-aldehyde N-Tosylhydrazones: Access to Functionalized 9-Amino-10-arylphenanthrenes

et al. 2018

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An efficient, general, and convenient protocol for the synthesis of functionalized 9-amino-10-arylphenanthrene derivatives using a catalystfree cascade reaction of arylboronic acids and 2′-cyano-biaryl-2-aldehyde Ntosylhydrazones is described. The synthesis was carried out via simple experimental conditions using Na 2 CO 3 in 1,4-dioxane as a solvent. Moreover, the 9-amino-10-arylphenanthrene compounds were also obtained on a gram scale and further derivatized to synthesize the fused phenanthrene derivatives.

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Section: Introductionmentioning

confidence: 99%

Cascade Reaction of Arylboronic Acids and 2′-Cyano-biaryl-2-aldehyde N-Tosylhydrazones: Access to Functionalized 9-Amino-10-arylphenanthrenes

et al. 2018

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ChemInform Abstract: Development of Non‐Peptidic Farnesyltransferase Inhibitors Based on the Ca₁a₂ of Ras‐CaaX.

et al. 2009

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Peptide scaffold‐derived peptidomimetic farnesyltransferase inhibitors

Yang

Wang

et al. 2021

J Chinese Chemical Soc

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Human protein farnesyltransferase (FTase) is involved in many essential signal transduction proteins and has been explored as druggable targets of diverse diseases such as cancer and inflammation. Here, we propose a new strategy termed as Peptide Scaffold‐derived Peptidomimetic FTase Inhibitors (PSPFI) to discover peptidomimetic lead molecular entities that can inhibit FTase. The strategy first defines a PSPFI‐oriented peptidomimetic library that contains >30,000 sulfhydryl/thioether‐carrying peptidomimetics, and then employs molecular docking calculation, multiple similarity analysis, structural minimization, and affinity scoring to screen against the library, in order to discover those peptidomimetics that share high similarity with the core binding module (CBM) of FTase Rap2a peptide substrate in 2D‐chemistry, 3D‐conformation, pharmacophore, and nonbonded pattern, as well as exhibit high theoretical affinity to FTase. Totally 56 hit peptidomimetics were identified from the library, from which we manually select 6 structurally diverse, purchasable peptidomimetics to perform FTase assays. Consequently, four are determined as potent FTase inhibitors (IC50 < 1 μM); their inhibitory activity is moderately lower than the sophisticated FTase inhibitor Tipifarnib and considerably higher than the native CBM peptide. These peptidomimetic ligands share similar extended conformation, binding mode, and Zn2+ coordination with Rap2a CBM peptide in FTase active site, but would have a different inhibition mechanism to Tipifarnib.

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Development of Non-peptidic Farnesyltransferase Inhibitors based on the Ca₁a₂of Ras-CaaX

Cited by 4 publications

References 14 publications

Cascade Reaction of Arylboronic Acids and 2′-Cyano-biaryl-2-aldehyde N-Tosylhydrazones: Access to Functionalized 9-Amino-10-arylphenanthrenes

Cascade Reaction of Arylboronic Acids and 2′-Cyano-biaryl-2-aldehyde N-Tosylhydrazones: Access to Functionalized 9-Amino-10-arylphenanthrenes

ChemInform Abstract: Development of Non‐Peptidic Farnesyltransferase Inhibitors Based on the Ca₁a₂ of Ras‐CaaX.

Peptide scaffold‐derived peptidomimetic farnesyltransferase inhibitors

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Development of Non-peptidic Farnesyltransferase Inhibitors based on the Ca1a2of Ras-CaaX

Cited by 4 publications

References 14 publications

Cascade Reaction of Arylboronic Acids and 2′-Cyano-biaryl-2-aldehyde N-Tosylhydrazones: Access to Functionalized 9-Amino-10-arylphenanthrenes

Cascade Reaction of Arylboronic Acids and 2′-Cyano-biaryl-2-aldehyde N-Tosylhydrazones: Access to Functionalized 9-Amino-10-arylphenanthrenes

ChemInform Abstract: Development of Non‐Peptidic Farnesyltransferase Inhibitors Based on the Ca1a2 of Ras‐CaaX.

Peptide scaffold‐derived peptidomimetic farnesyltransferase inhibitors

Contact Info

Product

Resources

About

Development of Non-peptidic Farnesyltransferase Inhibitors based on the Ca₁a₂of Ras-CaaX

ChemInform Abstract: Development of Non‐Peptidic Farnesyltransferase Inhibitors Based on the Ca₁a₂ of Ras‐CaaX.