geranylgeranyl

Geranylgeranyl pyrophosphate tetrabutylammonium(1：2) is one of the endogenous cholesterol and intermediates produced by the mevalerate pathway. Geranylgeranyl pyrophosphate tetrabutylammonium(1：2) is the common precursor of diterpenoids, for example, Paclitaxel. It can be used for cancer research.

(2E,6E,10E)-3,7,11,15-tetramethylhexadeca-2,6,10,14-tetraen-1-yl dihydrogen diphosphate,tetrabutylammonium(1:1.5) is a common precursor of taxadiene such as Paclitaxel.

Geranylgeranyl pyrophosphate, a key metabolite in protein geranylgeranylation, serves as the universal precursor for diterpenoids, such as Paclitaxel. Its role in cancer research stems from this critical function.

S-Geranylgeranyl-L-glutathione acts as a ligand for the orphan G protein-coupled receptor (GPCR) P2RY8, displaying selective affinity by inducing internalization of P2RY8 in preference to the sphingosine-1-phosphate receptor 2 (S1P2), GPR55, cysteinyl leukotriene receptor 1 (CysLT1 receptor), and the CysLT2 receptor at a concentration of 100 nM. Additionally, at a lower concentration of 10 nM, S-Geranylgeranyl-L-glutathione inhibits the chemokine (C-X-C motif) ligand 12-induced migration of both P2RY8-expressing WEHI-231 B cell lymphoma cells and human tonsil germinal center B cells.

N-acetyl-S-geranylgeranyl-L-Cysteine is a synthetic substrate for the isoprenylated protein methyltransferase (also known as S-adenosylmethionine-dependent methyltransferase). Because it is able to serve as a substrate for the methyltransferase, it effectively functions as an inhibitor of methylation of endogenous isoprenylated proteins.

Geranylgeranyl pyrophosphate is an intermediate in the HMG-CoA reductase pathway derived directly from farnesyl pyrophosphate and used in the biosynthesis of terpenes and terpenoids.[1] It is also serves as a substrate in the prenylation of a variety of critical intracellular proteins including small GTPases.[2] This post-translational modification is necessary for correct localization of proteins to intracellular membranes for proper functionality and has become a focus of anticancer drug discovery.[3][4]

GGTI 2147 decreased Rac1 activity, down-regulated p65 expression, and ameliorated OGD/R-induced neuronal apoptosis.

Perillyl Alcohol is a naturally occurring monoterpene related to limonene with antineoplastic activity. Perillyl alcohol (Isocarveol) inhibits farnesyl transferase and geranylgeranyl transferase, thereby preventing post-translational protein farnesylation and isoprenylation and activation of oncoproteins such as p21-ras, and arresting tumor cells in the G1 phase of the cell cycle.

Digeranyl bisphosphonate (DGBP) is a potent geranylgeranyl pyrophosphate (GGPP) synthase inhibitor that impedes the geranyl pyrophosphorylation of Rac1 and induces autophagy without causing apoptosis.

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).

hGGPPS-IN-2 is an analogue of C-2 substituted thienopyrimidinyl bisphosphonates (C2-ThP-BPs) and is a potent inhibitor of human geranylgeranyl pyrophosphate synthase (hGGPPS). hGGPPS-IN-2 targets multiple myeloma (MM) cells, induces selective apoptosis, and shows anti-myeloma effects in vivo. It has shown anti-myeloma effects in vivo.

FGTI-2734 mesylate, a RAS C-terminal mimetic compound with dual farnesyl transferase (FT) and geranylgeranyl transferase-1 (GGT) inhibitory activities (IC50s of 250 nM and 520 nM for FT and GGT, respectively), mitigates KRAS resistance by preventing its membrane localization, effectively impeding mutant KRAS patient-derived pancreatic tumors.

FTI-2148 is an inhibitor of RAS C-terminal mimetic dual farnesyl transferase (FT-1) and geranylgeranyl transferase-1 (GGT-1) (IC50s: 1.4 nM and 1.7 μM, respectively).

Geranyl pyrophosphate is an intermediate in the mevalonate pathway. It is formed from dimethylallyl pyrophosphate and isopentenyl pyrophosphate by geranyl pyrophosphate synthase. Geranyl pyrophosphate is used in the biosynthesis of farnesyl pyrophosphate , geranylgeranyl pyrophosphate , cholesterol, terpenes, and terpenoids.

FGTI-2734 is a dual farnesyl transferase (FT) and geranylgeranyl transferase-1 (GGT-1) inhibitor, exhibiting IC50 values of 250 nM and 520 nM for FT and GGT-1, respectively. It effectively prevents the membrane localization of KRAS, addressing the issue of KRAS resistance and inhibiting the growth of mutant KRAS patient-derived pancreatic tumors.

GGTI-2166 is a geranylgeranyl transferase I inhibitor. GGTI-2166 inhibit the pOC formation induced by RANKL or TNF-alpha in cultures of both mouse marrow-derived macrophage-colony-stimulating factor (M-CSF) dependent monocytes (MD cells) and the mouse monocyte cell line RAW 264.7 (RAW cells). GGTI-2166 inhibited TRAP activity induced by RANKL or TNF-alpha in both cell cultures and prevented the incorporation of [3H]all-trans geranylgeraniol into prenylated proteins in RAW cells.

FTI-2148 diTFA, a dual inhibitor targeting both farnesyl transferase (FT-1) and geranylgeranyl transferase-1 (GGT-1), functions as a RAS C-terminal mimetic. It exhibits potent inhibitory capabilities with IC50 values of 1.4 nM for FT-1 and 1.7 μM for GGT-1, respectively.

Compound 13h (hGGPPS-IN-3) is a potent inhibitor of human geranylgeranyl pyrophosphate synthase (hGGPPS), characterized as a C-2-substituted thienopyrimidine-based bisphosphonate analogue (C2-ThP-BPs). It selectively induces apoptosis in multiple myeloma (MM) cells and demonstrates antimyeloma activity in vivo [1].

(S)-(−)-Perillyl alcohol (Perillyl alcohol), a monoterpene found in lavender, inhibits Ras farnesylation, upregulates the mannose-6-phosphate receptor, induces apoptosis, and exhibits anti-cancer activity.