FNTB inhibitors bind FNTA:FNTB

Stable Identifier
Reaction [binding]
Homo sapiens
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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

Devine, A, Sanz, G, Skrzat, S, Angibaud, P, Fuery, CJ, Wouters, W, Applegate, TL, Poignet, H, Todd, AV, Venet, M, Smets, G, Bowden, C, End, DW

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

Desai, J, Njoroge, FG, Remiszewski, S, Deskus, J, Alvarez, CS, Ganguly, AK, Rane, DF, Kelly, J, Connolly, M, Afonso, A, Mallams, AK, Wong, J, del Rosario, J, Wang, J, Kirschmeier, P, Wang, L, Cooper, AB, Taveras, AG, Rossman, RR, Liu, YT, Wolin, R, Vibulbhan, B, Bishop, WR, Pinto, P, Patton, R

J. Med. Chem. 1998
21779505 Therapeutic strategies for targeting ras proteins

McCormick, F, Salt, M, Young, A, Gysin, S

Genes Cancer 2011
32877642 Growth Factor Receptor Signaling Inhibition Prevents SARS-CoV-2 Replication

Ciesek, S, Cinatl, J, Tascher, G, M√ľnch, C, Bojkova, D, Klann, K

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

Njoroge, FG, Remiszewski, S, Lee, S, Doll, RJ, Syed, J, Ferrari, E, Bryant, MS, Dell, J, Nomeir, AA, Korfmacher, WA, Chen, J, Malkowski, M, Nielsen, L, Girijavallabhan, VM, Yaremko, B, Lipari, P, Prioli, N, Liu, M, Lin, CC, Sinha, D, Catino, JJ, Mallams, AK, Wang, L, Taveras, AG, 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

Doll, RJ, Maxwell, E, Kirschmeier, P, Black, S, James, L, Taveras, AG, Carr, D, Ashar, HR, McGuirk, M, Bishop, WR, Gray, K, Armstrong, L

Exp. Cell Res. 2001
27396271 Drugging Ras GTPase: a comprehensive mechanistic and signaling structural view

Nussinov, R, Zhang, J, Gu, S, Lu, S, Jang, H

Chem Soc Rev 2016
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