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Table 2 Summary of Ras and Ras pathways modulators in the heart

From: Molecules linked to Ras signaling as therapeutic targets in cardiac pathologies

Group Molecule Mechanism of action References
Inhibitors of Angiotensin-II Candesartan Angiotensin-II AT1R receptor antagonist Established therapy of clinical cardiac hypertrophy and HF
Captopril Angiotensin-converting enzyme (ACE) inhibitor Established therapy of clinical cardiac hypertrophy and HF
Inhibitors of Ras farnesylation Statins Inhibits synthesis of farnesyl by inhibition of HMG-CoA reductase Lipid lowering therapy with broad clinical applications in cardiovascular prevention
Farnesyl transferase siRNA Inhibits expression of farnesyl transferase Improves pressure overload cardiac remodeling in mice [100]
FPT-III Farnesyl analog: inhibits farnesylation of Ras and other small GTPases Cardioprotective effect in ischemia–reperfusion related to ischemic pre-conditioning [90]
FTI-276 Tetrapeptid-mimetic, which inhibits FPPS Improved cardiac remodeling in spontaneously hypertensive rats [101]
Silencing-mRNA si-RNA-H-Ras Inhibits mRNA synthesis of H-Ras Inhibits cardiomyocyte hypertrophy in vitro by phenylephrine [25]
Signal inhibitors Cyclosporin A Calcineurin inhibitor Attenuates pressure overload cardiac hypertrophy but causes HF [106]
Rapamycin Akt inhibitor Prevented cardiac hypertrophy in a transgenic mouse model with SHP-2 active mutation [107]
PD0325901 MEK inhibitor Tested in cancer patients [111]
SB203580 p38 inhibitor Only tested in cancer cells
  1. Examples of molecules used to inhibit Ras and its pathways in the heart, experimentally in animal models or clinically in patients. To our knowledge, the anti-cancer molecules PD0325901 and SB203580 have not yet been used in cardiac diseases, but are of interest as inhibitors of Ras-related pathways (more details in paragraph 6 of the article)