gtpases

RBC8 is a specific GTPases RalA RalB inhibitor by inhibiting the binding of Ral to its effector RALBP1, no inhibition on the GTPases RhoA and Ras.

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.

1A-116 is a specific inhibitor of Rac1 .

Rhosin hydrochloride is a specific inhibitor of the RhoA subfamily Rho GTPases and inhibits the RhoA-GEF interaction. Rhosin hydrochloride can significantly induce cell apoptosis without affecting cell cycle progression. [1]

Rhosin is an effective and specific RhoA subfamily Rho GTPases inhibitor, which specifically binds to RhoA to inhibit RhoA-GEF interaction (Kd: ~ 0.4 uM). Rhosin does not interact with Cdc42 or Rac1, nor the GEF, LARG. Rhosin causes cell apoptosis.

Guanosine triphosphate tritris (GTP tritris) serves as a crucial enhancer in myocyte differentiation, playing an essential role in regulating miRNA-muscle regulatory factors. It promotes the release of exosomes rich in guanine and guanine-derived molecules, and is considered an activation precursor for RNA synthesis. In mitochondrial functionality, GTP is involved in the entry of proteins into the matrix, which is vital for various regulatory pathways. It initiates peptide synthesis by facilitating the binding of formylmethionine-tRNA to the ribosome, and aids in polypeptide chain elongation. Additionally, GTP acts as a carrier for phosphates and pyrophosphates, channeling chemical energy into specific biosynthetic pathways. It activates signal transduction G proteins, regulates cellular processes such as proliferation and differentiation, and its hydrolysis by small GTPases (including Ras and Rho) is indispensable for both proliferation and apoptosis. Furthermore, the small GTPase Rab assists in vesicle docking, fusion, and formation. Beyond signal transduction, GTP is also an energy-rich precursor in the biosynthesis of DNA and RNA enzymes.

BAY 593 functions as an inhibitor of geranylgeranyltransferase-I (GGTase-I), effectively preventing the activation of Rho-GTPases and consequently inactivating YAP1 TAZ signaling pathways. It has been shown to inhibit tumor growth dose-dependently in xenograft mouse models, exhibiting IC50 values of 38.4 nM in MT-1080 cells and 564 nM in MDA-MB-231 cells, as well as in PXF 541 xenografts.

ML-097 (CID-2160985) is a universal activator of Ras-related GTPases.

8-CPT-2Me-cAMP sodium is a sodium salt compound that selectively activates exchange proteins activated by cAMP (Epac), which are cAMP-sensitive guanine nucleotide exchange factors (GEFs) responsible for activating small GTPases Rap1 and Rap2. It specifically activates Epac1 with an EC50 value of 2.2 μM, while showing no activation of PKA with an EC50 value greater than 10 μM [1]. Additionally, 8-CPT-2Me-cAMP sodium stimulates the Epac-mediated release of calcium ions (Ca2+) in vitro in pancreatic β-cells [2].

Dynamin I inhibitor

pan activator of Ras-related GTPases

RBC10 inhibits the binding of Ral to its effector RALBP1, as well as inhibiting Ral-mediated cell spreading of murine embryonic fibroblasts and anchorage-independent growth of human cancer cell lines.

IMM-01 is a novel class of small-molecule agonists of the mammalian Diaphanous (mDia)-related formins, which act downstream of Rho GTPases to assemble actin filaments, and their organization with microfilaments to establish and maintain cell polarity during migration and asymmetric division. GTP-bound Rho activates mDia family members by disrupting the interaction between the DID and DAD autoregulatory domains, which releases the FH2 domain to modulate actin and microtubule dynamics[1].

Guanosine 5'-diphosphate (GDP) is a purine nucleotide and biosynthetic precursor of guanosine 5'-triphosphate .1It has been used to study the conformations of GTPases.2GDP (100 μM) activates sulfonylurea receptor 2B (SUR2B) linked to the inward-rectifier potassium channel 6.1 (Kir6.1) in HEK293T cells in a patch-clamp assay.3 1.Berg, J.M., Tymoczko, J.L., and Stryer, L.Biochemistry(2002) 2.Vetter, I.R., and Wittinghofer, A.The guanine nucleotide-binding switch in three dimensionsScience294(5545)1299-1304(2001) 3.Yamada, M., Isomoto, S., Matsumoto, S., et al.Sulphonylurea receptor 2B and Kir6.1 form a sulphonylurea-sensitive but ATP-insensitive K+ channelJ. Physiol.499(Pt 3)715-720(1997)

Dynamin-related GTPase DRP1 partial inhibitor (IC50 = 1.2 μM). Selective for DRP1 over other dynamin-related GTPases, OPA1 and DYN1. Increases mitochondrial DNA levels in mfn1- knockout MEFs deficient in mitochondrial fusion. Mallat et al (2018) Discovery and characterization of selective small molecule inhibitors of the mammalian mitochondrial division dynamin, DRP1. Biochem.Biophys.Res.Commun. 499 556 PMID:29601815

Inosine-5'-triphosphate trisodium salt (ITP) is used in studies on the impact of deamination of ATP and GTP by various enzymes and chemical processes. Inosine-5'-triphosphate trisodium salt (ITP) may be used as a substrate to study the specificity and kinetics of nucleoside-5′-triphosphatase and ATPase. Inosine-5'-triphosphate trisodium salt (ITP) is also used to study activation of various ATPases and GTPases.

Guanosine 5'-triphosphate trisodium salt (5'-GTP trisodium salt) activates signal-transducing G proteins involved in cellular processes such as proliferation, differentiation, and activation of intracellular kinase cascades. It regulates proliferation and apoptosis through the hydrolysis by small GTPases Ras and Rho, and plays a role in vesicle docking, fusion, and formation via Rab. Additionally, GTP serves as an energy-rich precursor for the biosynthesis of DNA and RNA.

PKN1 2-IN-1 is a potent and selective PKN2 inhibitor with 14-fold higher selectivity for PKN2 than PKN1, membrane permeability and anticancer potential.Protein kinase N proteins (PKN1, PKN2 and PKN3) are effectors of Rho GTPases and are critical for survival in several tumor cell lines including prostate and breast cancer.

CID-1067700 is one of the first identified competitive inhibitors of nucleotide binding by Ras-related GTPases(Rab7 with a Ki of 13 nM).

MLS000532223 is a selectiveRho family GTPases inhibitor(EC50 : 16 μM to 120 μM).

ARN22089, an orally active novel class of trisubstituted pyrimidine, inhibits the interaction of CDC42 GTPases with specific downstream effectors and blocks tumor growth in a BRAF mutant mouse melanoma model [1].

Morelloflavone is a biflavonoid derived from Garcinia cambogia with anticancer property that inhibits tumor angiogenesis by targeting Rho GTPases and the extracellular signal-regulated kinase (ERK) signaling pathway. Fukugetin inhibits the cellular proliferation of a variety of cancer cell lines, such as Caspase-9, TNF -α, ER-α, , HER-2.

Rac GTPase fragment is a peptide with the sequence H2N-Val-Phe-Asp-Glu-Ala-Ile-Arg-Ala-Val-OH, MW= 1019.15. Rac is a subfamily of the Rho family of GTPases, small signaling G proteins (more specifically a GTPase).