Reactome | FNTB inhibitors bind FNTA:FNTB

FNTB inhibitors bind FNTA:FNTB

Stable Identifier

R-HSA-9647987

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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Because prenylation is important for RAS membrane localization and function, inhibition of this step of RAS processing was viewed as a promising early therapeutic target for RAS-driven cancers (reviewed in Gysin et al, 2011). Farnesyltransferase inhibitors such as lonafarnib and tipifarnib are small molecule CaaX competitive inhibitors that inhibit cell growth of a range of cancer cell lines and tumor xenografts (Njoroge et al, 1998; End et al, 2001; Liu et al, 1998; Ashar et al, 2001). Unfortunately, the clinical use of these drugs is hampered by the fact that both KRAS and NRAS can be geranylgeranylated when FTase is inhibited, restoring membrane localization and function (Fiordalisi et al, 2003). FTase inhibitors may have clinical use in the treatment of HRAS driven cancers, such as bladder and thyroid cancers (reviewed in Gysin et al, 2011; Lu et al, 2016).

Lonafarnib is a farnesyltransferase inhibitor of growth factor signalling that prevented SARS-CoV-2 replication in Caco-2 and UKF-RC-2 cells at clinically achievable concentrations (Klann et al, 2020).

Literature References

PubMed ID	Title	Journal	Year
11196150	Characterization of the antitumor effects of the selective farnesyl protein transferase inhibitor R115777 in vivo and in vitro End, DW, Smets, G, Todd, AV, Applegate, TL, Fuery, CJ, Angibaud, P, Venet, M, Sanz, G, Poignet, H, Skrzat, S, Devine, A, Wouters, W, Bowden, C	Cancer Res.	2001
9822558	(+)-4-[2-[4-(8-Chloro-3,10-dibromo-6,11-dihydro-5H-benzo[5, 6]cyclohepta[1,2-b]- pyridin-11(R)-yl)-1-piperidinyl]-2-oxo-ethyl]-1-piperidinecarboxamid e (SCH-66336): a very potent farnesyl protein transferase inhibitor as a novel antitumor agent Njoroge, FG, Taveras, AG, Kelly, J, Remiszewski, S, Mallams, AK, Wolin, R, Afonso, A, Cooper, AB, Rane, DF, Liu, YT, Wong, J, Vibulbhan, B, Pinto, P, Deskus, J, Alvarez, CS, del Rosario, J, Connolly, M, Wang, J, Desai, J, Rossman, RR, Bishop, WR, Patton, R, Wang, L, Kirschmeier, P, Ganguly, AK	J. Med. Chem.	1998
21779505	Therapeutic strategies for targeting ras proteins Gysin, S, Salt, M, Young, A, McCormick, F	Genes Cancer	2011
32877642	Growth Factor Receptor Signaling Inhibition Prevents SARS-CoV-2 Replication Klann, K, Bojkova, D, Tascher, G, Ciesek, S, Münch, C, Cinatl, J	Mol Cell	2020
9810004	Antitumor activity of SCH 66336, an orally bioavailable tricyclic inhibitor of farnesyl protein transferase, in human tumor xenograft models and wap-ras transgenic mice Liu, M, Bryant, MS, Chen, J, Lee, S, Yaremko, B, Lipari, P, Malkowski, M, Ferrari, E, Nielsen, L, Prioli, N, Dell, J, Sinha, D, Syed, J, Korfmacher, WA, Nomeir, AA, Lin, CC, Wang, L, Taveras, AG, Doll, RJ, Njoroge, FG, Mallams, AK, Remiszewski, S, Catino, JJ, Girijavallabhan, VM, Bishop, WR	Cancer Res.	1998
11120601	The farnesyl transferase inhibitor SCH 66336 induces a G(2) --> M or G(1) pause in sensitive human tumor cell lines Ashar, HR, James, L, Gray, K, Carr, D, McGuirk, M, Maxwell, E, Black, S, Armstrong, L, Doll, RJ, Taveras, AG, Bishop, WR, Kirschmeier, P	Exp. Cell Res.	2001
27396271	Drugging Ras GTPase: a comprehensive mechanistic and signaling structural view Lu, S, Jang, H, Gu, S, Zhang, J, Nussinov, R	Chem Soc Rev	2016