Implications of farnesyltransferase and its inhibitors as a promising strategy for cancer therapy

Клочков, С. Г.; Neganova, Margarita E.; Yarla, Nagendra Sastry; Parvathaneni, Madhukiran; Sharma, Bechan; Tarasov, Vadim V.; Barreto, George E.; Бачурин, С. О.; Ashraf, Ghulam Md; Aliev, Gjumrakch

doi:10.1016/j.semcancer.2017.10.010

Cited by 32 publications

(24 citation statements)

References 107 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To identify useful natural products, numerous isoprenoids are of significant commercial value owing to their broad-spectrum clinical and industrial applications (Tables 1 and 2). 19,[128][129][130][131][132][133][134][135][136][137][138][139][140][141][142][143][144][145] At present, the screening, isolation, and identification of new forms of natural compounds with pharmacological properties have gained increasing attention in academia and industry. In recent preclinical and clinical studies, the number of newly identified natural products with therapeutic efficacy in humans against diseases such as cancer, hepatitis, osteoporosis, and respiratory tract diseases has rapidly increased.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, some of these inhibitors have been assessed in clinical trials. 24,[128][129][130][131][132] Another natural cyclic monoterpenoid, limonene, a major component of fruit-derived essential oils, is a flavoring agent in food manufacturing. Research on its D-form isomer, dlimonene, has progressed to phase one clinical studies for breast, parotid, and submandibular gland cancers (Figure 8c, Tables 1 and 2).…”

Section: Structural and Functional Analysesmentioning

confidence: 99%

“…Over the past few years, numerous analogs, including natural isoprenoids, have been synthesized or extracted and subsequently used in investigations into various aspects of the prenylation reaction including its mechanisms, protein structures, enzyme kinetics, and prenylated proteomes. Moreover, some of these inhibitors have been assessed in clinical trials 24,128–132 . Wu et al extracted natural terpenoid antroquinonols from Antrodia camphorate , 133 which may inhibit the activity of FTase and GGTase in cancer cells; in turn, this may inhibit the function of Ras and Ras‐related GTP‐binding proteins.…”

Section: Class 6: Protein Prenylationmentioning

confidence: 99%

See 2 more Smart Citations

Structure, catalysis, and inhibition mechanism of prenyltransferase

Chang¹,

Cheng²,

Wang

2020

IUBMB Life

View full text Add to dashboard Cite

Isoprenoids, also known as terpenes or terpenoids, represent a large family of natural products composed of five-carbon isopentenyl diphosphate or its isomer dimethylallyl diphosphate as the building blocks. Isoprenoids are structurally and functionally diverse and include dolichols, steroid hormones, carotenoids, retinoids, aromatic metabolites, the isoprenoid side-chain of ubiquinone, and isoprenoid attached signaling proteins. Productions of isoprenoids are catalyzed by a group of enzymes known as prenyltransferases, such as farnesyltransferases, geranylgeranyltransferases, terpenoid cyclase, squalene synthase, aromatic prenyltransferase, and cis-and trans-prenyltransferases. Because these enzymes are key in cellular processes and metabolic pathways, they are expected to be potential targets in new drug discovery. In this review, six distinct subsets of characterized prenyltransferases are structurally and mechanistically classified, including (1) head-to-tail prenyl synthase, (2) head-to-head prenyl synthase, (3) head-tomiddle prenyl synthase, (4) terpenoid cyclase, (5) aromatic prenyltransferase, and (6) protein prenylation. Inhibitors of those enzymes for potential therapies against several diseases are discussed. Lastly, recent results on the structures of integral membrane enzyme, undecaprenyl pyrophosphate phosphatase, are also discussed.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Structural and Functional Analysesmentioning

confidence: 99%

Section: Class 6: Protein Prenylationmentioning

confidence: 99%

See 1 more Smart Citation

Structure, catalysis, and inhibition mechanism of prenyltransferase

Chang¹,

Cheng²,

Wang

2020

IUBMB Life

View full text Add to dashboard Cite

show abstract

“…Approaches have focused on the post-translational modification of RAS isoforms by prenylation (addition of farnesyl or geranyl-geranyl moieties) required for their correct localization to the plasma membrane. The farnesyltransferase inhibitors (FTIs) to farnesyl-transferase (FTase), the enzyme catalyzing the prenylation of HRAS have been developed to combat the transforming activities of oncogenic RAS [45]. While showing high preclinical anti-cancer activity in tumors driven by H-RAS, FTIs are not effective against N-RAS and K-RAS.…”

Section: Inhibiting Ras Signaling In Nf1-deficient Cellsmentioning

confidence: 99%

Emerging therapeutic targets for neurofibromatosis type 1

Walker

Upadhyaya

2018

Expert Opinion on Therapeutic Targets

View full text Add to dashboard Cite

Neurofibromatosis type 1 (NF1) is an autosomal dominantly inherited tumor predisposition syndrome with an incidence of one in 3000-4000 individuals with no currently effective therapies. The NF1 gene encodes neurofibromin, which functions as a negative regulator of RAS. NF1 is a chronic multisystem disorder affecting many different tissues. Due to cell-specific complexities of RAS signaling, therapeutic approaches for NF1 will likely have to focus on a particular tissue and manifestation of the disease. Areas covered: We discuss the multisystem nature of NF1 and the signaling pathways affected due to neurofibromin deficiency. We explore the cell-/tissue-specific molecular and cellular consequences of aberrant RAS signaling in NF1 and speculate on their potential as therapeutic targets for the disease. We discuss recent genomic, transcriptomic, and proteomic studies combined with molecular, cellular, and biochemical analyses which have identified several targets for specific NF1 manifestations. We also consider the possibility of patient-specific gene therapy approaches for NF1. Expert opinion: The emergence of NF1 genotype-phenotype correlations, characterization of cell-specific signaling pathways affected in NF1, identification of novel biomarkers, and the development of sophisticated animal models accurately reflecting human pathology will continue to provide opportunities to develop therapeutic approaches to combat this multisystem disorder.

show abstract

“…Albeit different strategies (i.e., tacking the downstream effector MEK) have been envisaged in NSCLC, researchers and clinicians dedicated to lung cancer know how challenging and frustrating is to deal with RAS members (14). Moreover, specifically developed anti-geranylation and/or -farnesylation agents have still not found their definite place in clinical oncology (15,16). Nevertheless, in the oncology field it is not so uncommon to see strategies, presented as wonderful in the preclinical setting, collapse at the first clinical test, as well as the opposite scenario is possible.…”

Section: Editorialmentioning

confidence: 99%