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).

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

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.

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.

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.

GGTI 2133, a peptidomimetic inhibitor of geranylgeranyl transferase type I (GGTase I; IC50= 38 nM), exhibits 140-fold selectivity towards GGTase I compared to farnesyltransferase (IC50= 5,400 nM). The compound effectively inhibits the geranylgeranylation of RAP1A (IC50= 10 µM) without affecting the farnesylation of H-Ras (IC50= >30 µM). Moreover, GGTI 2133 reduces the growth, migration, and invasion of oral squamous cell carcinoma (OSSC) cells to 75, 45, and 27% of control levels, respectively. When administered intraperitoneally at 5 mg/kg per day, it prevents eosinophil infiltration into the airways in a mouse model of allergic bronchial asthma, although it does not reduce chemokine levels. Additionally, GGTI 2133 thwarts naloxone-induced contraction of ileum in rats experiencing morphine withdrawal syndrome and mitigates the severity of withdrawal symptoms in vivo (ED50= 0.076 mg/kg).

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.

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.

Eicosapentaenoic Acid (EPA) sodium, an orally active omega-3 long-chain polyunsaturated fatty acid (ω-3 LC-PUFA), demonstrates a unique ability to demethylate DNA, thereby facilitating the re-expression of the tumor suppressor gene CCAAT enhancer-binding protein δ (C EBPδ). This compound also activates the RAS ERK C EBPβ pathway by demethylating H-Ras intron 1 CpG island in U937 leukemia cells and promotes the relaxation of vascular smooth muscle cells, leading to vasodilation.

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).

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).

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.

(Rac)-Lonafarnib (Sch66336 racemate) is the racemic form of the potent, orally active farnesyl transferase (FTase) inhibitor, Lonafarnib. It effectively inhibits H-ras, K-ras, and N-ras with IC50 values of 1.9 nM, 5.2 nM, and 2.8 nM, respectively, and exhibits activities against the hepatitis delta virus (HDV).

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.

GGTI-286 TFA is a potent, cell-permeable inhibitor of GGTase I, exhibiting 25 times greater effectiveness (IC 50 = 2 μM) compared to the corresponding methyl ester of FTI-276. It specifically targets the geranylgeranylation of Rap1A, demonstrating significant selectivity over the farnesylation of H-Ras in NIH3T3 cells (IC 50s = 2 and >30 μM, respectively). Additionally, GGTI-286 TFA effectively inhibits the stimulation of oncogenic K-Ras4B with an IC 50 of 1 μM.

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