Chaetomella acutiseta produces chaetomellic acids A and B which are reversible inhibitors of farnesyl-protien transferase

Lingham, Russell B.; Silverman, Keith C.; Bills, Gerald F.; Cascales, Carmen; Sanchez, Manual; Jenkins, Rosalind G.; Gartner, Suzanne; Martin, I.; Dı́ez, Maria Teresa; Peláez, Fernando; Mochales, S.; Kong, Y L; Burg, Richard W.; Meinz, María; Huang, Leeyuan; Nallin-Omstead, Mary; Mosser, Scott D.; Schaber, Michael D.; Omer, Charles A.; Pompliano, David L.; Gibbs, Jackson B.; Singh, Sheo B.

doi:10.1007/bf00170395

Cited by 46 publications

(22 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All the compounds were evaluated in the Ras farnesyl-protein transferase assay using human recombinant FPTase enzyme as described earlier (7)(8)(9). Barceloneic acid A [1} inhibited the FPTase enzyme with an IC50 value of 40 µ .…”

Section: And Discussionmentioning

confidence: 99%

Barceloneic Acid A, a New Farnesyl-Protein Transferase Inhibitor from a Phoma Species

Jayasuriya¹,

Ball²,

Zink³

et al. 1995

J. Nat. Prod.

Self Cite

View full text Add to dashboard Cite

Three new diphenyl ethers, barceloneic acids A, B, and barceloneic lactone [1, 2, and 3, respectively] were isolated from a fermentation extract of a fungus of the genus Phoma. The structures of compounds 1-3 were determined by a combination of spectroscopic and single-crystal X-ray diffraction methods. The effect of these compounds on the inhibition of farnesyl-protein transferase (FPTase) was evaluated and results are presented. Barceloneic acid A [1] is a novel and modest inhibitor of FPTase with an IC50 value of 40 microM.

show abstract

Section: And Discussionmentioning

confidence: 99%

Barceloneic Acid A, a New Farnesyl-Protein Transferase Inhibitor from a Phoma Species

Jayasuriya¹,

Ball²,

Zink³

et al. 1995

J. Nat. Prod.

Self Cite

View full text Add to dashboard Cite

show abstract

“…41,42 Additionally, a number of microbially derived inhibitors that resemble FPP in structure and are competitive with FPP in the farnesylation reaction have been isolated. [43][44][45][46][47][48][49][50][51][52] Surprisingly, several peptide-based inhibitors that compete with FPP have also been described 53,54 (for example, PD 083176; FIG. 1).…”

Section: Development Of Fptase Inhibitorsmentioning

confidence: 99%

Farnesyltransferase Inhibitors: Preclinical Development

Kohl

1999

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

The Ras proteins are low molecular weight GTP binding proteins that function in the regulation of the transduction of growth proliferative signals from the membrane to the nucleus. Oncogenically mutated ras genes are found in approximately 25% of all human cancers. Localization of the Ras oncoproteins to the inner surface of the plasma membrane is essential for their biological activity. This observation suggested that the enzyme that mediates the membrane localization, farnesyl-protein transferase (FPTase), would be a target for the development of novel anticancer agents. We have developed potent, cell-active inhibitors of FPTase that exhibit antiproliferative activity in cell culture and block the morphologic alterations associated with Ras-induced transformation of mammalian cells in monolayer cultures. In vivo, these compounds block the growth of ras-transformed fibroblasts in a nude mouse xenograft model and block the growth and, in some cases, cause regression of mammary and salivary tumors in several strains of ras transgenic mice in the absence of any detectable side effects. The results of our preclinical studies and those of others suggest that FTIs may have utility against a variety of human cancers, a hypothesis that is currently being tested in the clinic.

show abstract

“…Subsequently, compounds 76 and 77 were confirmed to have reversible inhibitory abilities against FTase (IC 50 ¼ 55 and 185 nM), and selective inhibitory abilities against bovine brain GGTase (IC 50 ¼ 92 and 54 lM) 25 . Lingham et al 101 further verified that compounds 76 and 77, similar to FPP, are reversible inhibitors of FTase. Singh et al 26 synthesised the isomeric diacids (78,79,80,81) of chaetomellic acids A and B, together with C-12 chain compound chaetomellic acid C (82) and its isomers (83,84).…”

Section: Polycarboxylic Acidsmentioning

confidence: 94%

An overview on natural farnesyltransferase inhibitors for efficient cancer therapy

Dai

Sun

Zhang

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

View full text Add to dashboard Cite

As one of the world's five terminally ills, tumours can cause important genetic dysfunction. However, some current medicines for tumours usually have strong toxic side effects and are prone to drug resistance. Studies have found that farnesyltransferase inhibitors (FTIs) extracted from natural materials have a good inhibiting ability on tumours with fewer side effects. This article describes several FTIs extracted from natural materials and clarifies the current research progress, which provides a new choice for the treatment of tumours.

show abstract

Chaetomella acutiseta produces chaetomellic acids A and B which are reversible inhibitors of farnesyl-protien transferase

Cited by 46 publications

References 22 publications

Barceloneic Acid A, a New Farnesyl-Protein Transferase Inhibitor from a Phoma Species

Barceloneic Acid A, a New Farnesyl-Protein Transferase Inhibitor from a Phoma Species

Farnesyltransferase Inhibitors: Preclinical Development

An overview on natural farnesyltransferase inhibitors for efficient cancer therapy

Contact Info

Product

Resources

About