H-Ras

Lonafarnib (Sch66336) is an orally bioavailable FPTase inhibitor for H-ras, K-ras-4B, and N-ras (IC50: 1.9 5.2 2.8 nM).

BMS-214662 is a selective farnesyl transferase inhibitor with antitumor activity, useful in studies of pancreatic, head and neck, and lung cancers.

J-104871 (UNII-6137X5QNJF) is a novel farnesyltransferase (FTase) inhibitor that competitively blocks Ras farnesylation in vivo, inhibits Ras processing in activated H-ras-transformed NIH3T3 cells, and suppresses tumor growth in nude mice transplanted with activated H-ras-transformed NIH3T3 cells.

LB42708 is an orally active farnesyltransferase (FTase) inhibitor (IC50: 0.8 1.2 2.0 nM toward H N K-ras).

Eicosapentaenoic Acid (EPA) is a ω-3 fatty acid abundantly available in marine organisms.

A-176120 is a potent farnesyl pyrophosphate (FPP) analogues, it selectively inhibits farnesyltransferase. It has anti-angiogenic potential and may reduce H-ras NIH3T3 tumour growth.

Kobe0065 is a novel and effective small-molecule compound that inhibits the Ras-Raf interaction by structure-based drug design (SBDD); it displays potent activity, competitively inhibiting the binding of H-Ras·GTP to c-Raf-1 RBD with a Ki value of 46 ± 13 μM.

FTI-277 hydrochloride (FTI 277 HCl) is an effective and specific farnesyltransferase (FTase) inhibitor (IC50: 500 pM); this selectivity is about 100-fold than the closely related GGTase I.

Kobe 2602 is an inhibitor of Ras that exhibits anticancer chemotherapeutic activities.

MLS-573151 is a selective inhibitor of GTPase Cdc42(EC50 of 2 μM). It is inactive against other GTPases family members, such as Rab2, Rab7, H-Ras, Rac1, Rac 2 and RhoA wild-type. MLS-573151 acts by blocking the binding of GTP to Cdc42.

K-Ras-IN-1, a K-Ras inhibitor, is characterized by its chemical formula C20H19ClN4O2S and is also known as N-[(1S)-3-cyclopropyl-1-[(6-fluoro-1H-benzimidazol-2-yl)sulfanyl]-2-oxo-1-(phenylmethyl)propyl]-4-fluorobenzenesulfonamide (compound [18, dashboard 819041] in brackets).

1. 3-Dehydrotrametenolic acid can be a potential anticancer agent against H-ras transformed tumor. 2. Dehydrotrametenolic acid is a promising candidate for a new type of insulin-sensitizing drug.

FTI-2153 is a potent and highly selective farnesyltransferase (FTase) inhibitor (IC50: 1.4 nM) that is over 3000-fold more effective at blocking H-Ras (IC50: 10 nM) than Rap1A processing.

BBO-10203 (Compound 758) binds to the RBD region of PI3Kα, hindering the interaction of K-, H-, and N-Ras with PI3Kα. It inhibits pAKT with an IC50 of less than 0.1 pM in BT474 cells.

CRT-0066854 is a PKCι and PKCζ inhibitor. CRT0066854 was able to restore polarized morphogenesis in the dysplastic H-Ras spheroids.

CP-609754 (LNK-754) is a potent and reversible farnesyltransferase inhibitor with potential anticancer activity. It inhibits farnesylation of recombinant human H-Ras (IC50=0.57 ng mL) and K-Ras (IC50=46 ng mL)[1]. In 3T3 H-ras (61L)-transfected cell lines, CP-609754 exhibits a slow on off rate, inhibiting mutant H-Ras farnesylation with an IC50 of 1.72 ng mL[1]. The compound is competitive for the prenyl acceptor (H-Ras protein) and noncompetitive for the prenyl donor farnesyl PPI, selectively inhibiting farnesylation of both H- and K-Ras proteins in 3T3 transfectants[1]. In vivo, CP-609754 shows antitumor activity against 3T3 H-ras (61L) tumors, with tumor regression achieved at 100 mg kg twice daily and an ED50 for tumor growth inhibition at 28 mg kg[1]. Continuous i.p. infusion of CP-609754 inhibits tumor growth by over 50% and reduces tumor farnesyltransferase activity by over 30% when plasma concentration is maintained above 118 ng mL[1]. [1]. Stacy L Moulder, et al. A phase I open label study of the farnesyltransferase inhibitor CP-609,754 in patients with advanced malignant tumors. Clin Cancer Res. 2004 Nov 1;10(21):7127-35.

FTI 277 TFA is a prodrug form of FTI 276 that inhibits farnesyltransferase (FTase) (IC50 = 0.5 nM). Inhibits H-Ras and K-Ras processing in whole cells (IC50 values are 0.1 and 10μM respectively) and disrupts constitutive H-Ras-specific activation of MAPK. Causes significant antiproliferative effects in human malignant glioma cells and many other tumor cell lines.

GGTI-286 is a potent, cell permeable GGTase I inhibitor (IC50: 2 μM). GGTI-286 inhibits Rap1A geranylation in NIH3T3 cells (IC50: 2 μM) more potently than H-Ras farnesylation (IC50>30 μM). Ras4B stimulation (IC50: 1 μM).

FTI-277 is a farnesyltransferase FTase inhibitor and a potent Ras CAAX peptide mimetic.FTI-277 inhibits H-Ras and K-Ras signaling and inhibits hepatitis delta virus (HDV) infection.

GGTI-286 hydrochloride is a potent inhibitor of GGTase I (IC50: 2 μM) and is also effective in inhibiting K-Ras4B (IC50: 1 μM). farnesylation (IC50=2 and >30 μM).

FTI-2153 TFA is a highly selective and potent inhibitor of the farnesyltransferase (FTase) enzyme (IC50: 1.4 nM). The inhibition activity was more than 3000 times that of Rap1A protein processing.

BMS-214662 is a Farnesyltransferase inhibitor , is also a nonsedating benzodiazepine derivative with potential antineoplastic activity. BMS-214662 inhibits the enzyme farnesyltransferase and the post-translational farnesylation of number of proteins involved in signal transduction, which may result in the inhibition of Ras function and apoptosis in susceptible tumor cells. This agent may reverse the malignant phenotype of H-Ras-transformed cells and has been shown to be active against tumor cells with and without Ras mutations.

XR3054 is a novel inhibitor of farnesyl protein transferase (FPTase). XR3054 inhibited the proliferation of the prostatic cancer cell lines LnCAP and PC3 and the colon carcinoma SW480 and HT1080 (IC50 values of 12.4, 12.2, 21.4 and 8.8 microM, respectively) but was relatively inactive when tested against a panel of breast carcinoma cell lines. The activity did not relate to the presence of mutant or wild-type ras in the cell lines tested. In conclusion XR3054 inhibits ras farnesylation, MAP kinase activation and anchorage-independent growth in NIH 3T3 transformed with v12 H-ras. Since the antiproliferative effect of the compound is not related to the ras phenotype, XR3054 may also have effects on other cell signaling mechanisms.

LB42908 is a highly potent Ras farnesyltransferase inhibitor(IC(50)=0.9 nM against H-Ras and 2.4 nM against K-Ras) with potential anticancer activity.