gtpase

RAS GTPase inhibitor 1 is a RAS GTPase inhibitor with potential antitumor activity.

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).

Mdivi-1 (Mitochondrial division inhibitor 1) is a mitochondrial division inhibitor that inhibits DRP1 and Dynamin I (IC50=1-10 μM). Mdivi-1 inhibits mitochondrial autophagy.

Tyrphostin 8(4-Hydroxybenzylidenemalononitrile) is a potent GTPase inhibitor that inhibits EGFR kinase with an IC50 of 560 μM.Tyrphostin 8 inhibits protein serine/threonine calmodulin phosphatases (IC50=21 μM), enhances transferrin receptor-mediated transcytosis in Caco-2 cells, and increases the hypoglycemic effect of oral insulin-transferrin. hypoglycemic effect.

CID-4785700 is a potent pan-GTPase inhibitor that inhibits Rab7 and inhibits the fungal histone acetyltransferase Rtt109 that binds to Asf1 and Vps75, and can be used in the study of lupus.

Dynamin inhibitory peptide Acetate is a peptide with the sequence Gln-Val-Pro-Ser-Arg-Pro-Asn-Arg-Ala-Pro that inhibit the GTPase dynamin.

Dynamin IN-2 (compound 43) is a Wiskostatin analogue. Dynamin IN-2 is a potent dynamin inhibitor (dynamin I GTPase, IC50= 1.0 μM). Dynamin IN-2 blocks clathrin mediated endocytosis (CME) (IC50= 9.5 μM).

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].

P110 TFA is a dynamin-related protein 1 (Drp1) inhibitor, inhibits Drp1 GTPase activity.

CCR-11 is a tannin-containing derivative with antimicrobial activity. CCR-11 inhibits the proliferation of B. subtilis and HeLa cells. CCR-11 inhibits bacterial proliferation and bacterial cytoplasmic division by inhibiting FtsZ assembly and GTPase activity. CCR-11 has potential anti-tumor activity and can be used to study breast cancer and pediatric myelodysplasia.

AZD4747 is a selective and potent inhibitor of the mutant GTPase KRASG12C that crosses the blood-brain barrier and has potential antitumor activity for the study of pancreatic and colorectal adenocarcinoma.

Anti-inflammatory agent 49 is a potent inhibitor of Drp1-Fis1 interaction, inhibits GTPase, and can be used in the study of diseases caused by mitochondrial dysfunction.

Dynasore (Dynamin Inhibitor I), a cell-permeable chemical, can reversibly and non-competitivity inhibit GTPase activity of dynamin 1/2 (IC50: 15 μM in a cell-free assay). It also inhibits the mitochondrial dynamin Drp1, with no effect against other small GTPase.

NSC 23766 trihydrochloride (Rac1 Inhibitor) is an inhibitor of Rac GTPase targeting Rac activation by GEFs (IC50: ~50 μM); no inhibitory for the closely related targets, RhoA or Cdc42.

ML141 (CID-2950007) is an effective, specific and reversible non-competitive inhibitor of Rho family GTPase cdc42 (IC50: 200 nM).

EHT 1864 is a effective Rac family GTPase inhibitor for Rac1/Rac1b/Rac2/Rac3 (Kd: 40/50/60/250 nM).

QS11 is a GTPase activating protein of ADP-ribosylation factor 1 (ARFGAP1) inhibitor. Modulates ARF-GTP levels and synergizes with the Wnt/β-catenin signaling pathway to upregulate β-catenin nuclear translocation. Also reduces in vitro migration of metastatic human breast cancer cells.

Hydroxy-Dynasore (Dyngo-4a) , a effective dynamin inhibitor, inhibits withDynI (brain), DynI (rec), and DynII (rec) of IC50 of 0.38 μM, 1.1 μM, and 2.3 μM, respectively.

EHop-016 is a specific Rac GTPase inhibitor with IC50 of 1.1 μM for Rac1 in MDA-MB-231 and MDA-MB-435 cells, equally effective inhibition for Rac3.

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.

RTIL 13 is a highly effective inhibitor of dynamin GTPase, exhibiting an IC50 value of 2.3 μM for dynamin I GTPase. Furthermore, it selectively interacts with the pleckstrin homology lipid binding domain. This compound effectively suppresses both receptor-mediated and synaptic vesicle endocytosis, demonstrating IC50 values of 9.3 μM and 7.1 μM, respectively.

The phosphatidylinositol phosphates represent a small percentage of total membrane phospholipids. However, they play a critical role in the generation and transmission of cellular signals. PtdIns-(3,4,5)-P3 can serve as an anchor for the binding of signal transduction proteins bearing pleckstrin homology (PH) domains. Centuarin α and the Akt-family of GTPase activating proteins are examples of PtdIns-(3,4,5)-P3-binding proteins. Protein-binding to PtdIns-(3,4,5)-P3 is important for cytoskeletal rearrangements and membrane trafficking. PtdIns-(3,4,5)-P3 is resistant to cleavage by PI-specific phospholipase C (PLC). Thus, it is likely to function in signal transduction as a modulator in its own right, rather than as a source of inositol tetraphosphates. For further reading on inositol phospholipids, see also references and .

Sordarin is an inhibitor of fungal protein synthesis originally isolated from S. araneosa.[1] It binds to elongation factor 2 (EF-2) in the presence of ribosomes and inhibits the uncoupled GTPase activity of equimolar mixtures of EF-2 and ribosomes from C. albicans (IC50 = 0.1 μM). Sordarin inhibits protein synthesis in cell-free lysates of C. albicans, C. glabrata, and C. neoformans (IC50s = 0.01, 0.2, and 0.06 μg/ml, respectively) but not in rabbit reticulocytes (IC50 = >100 μg/ml).[1] [2] It inhibits the growth of C. albicans (MIC = 8 μg/ml) but not C. glabrata or C. neoformans (MICs = >125 μg/ml).

Promotes proteasomal degradation of Miro1 (mitochondrial Rho GTPase 1). Reduces Miro1 levels in fibroblasts from Parkinson's disease (PD) patients (IC50 = 7.8 μM). Exhibits no significant effect on related outer mitochondrial membrane protein Mitofusin. Reduces stress-induced degeneration of dopaminergic neurons derived from PD patient iPSCs. Rescues age-dependent neuronal loss and prolongs lifespan in fly PD models.

Dynamin-related protein 1 (Drp1) inhibitor, inhibits Drp1 GTPase activity. Displays no effect on dynamin 1 or other mitochondrial dynamics-related proteins. Inhibits mitochondrial fission, dysfunction and reactive oxygen species (ROS) production in vitro.

(-)-Viriditoxin is a mycotoxin originally isolated from A. viridinutans that has antibacterial and antiproliferative activity. It is active against methicillin-sensitive and -resistant S. aureus (MSSA and MRSA, respectively), tetracycline-sensitive and -resistant Staphylococcus, vancomycin-sensitive and -resistant Enterococcus, and penicillin-sensitive and -resistant S. pneumoniae (MICs = 2-32 μg/ml). (-)-Viriditoxin is also active against fish pathogens, including S. iniae and S. parauberis (MICs = 0.16-0.21 μg/ml). It inhibits polymerization and the GTPase activity of E. coli FtsZ, a tubulin-like GTPase involved in bacterial cell division (IC50s = 8.2 and 7 μg/ml, respectively). (-)-Viriditoxin inhibits proliferation of human DU145, LNCaP, and PC3 prostate cancer cells (IC50s = 5.36, 0.63, and 7.6 μM, respectively) . It is also toxic to mice (LD50 = 2.8 mg/kg, i.p.).

mP6 (Myr-FEEERA-OH), a myristoylated peptide, selectively inhibits Gα 13's interaction with integrin β 3 while preserving talin-dependent integrin function. Additionally, mP6 impedes the GTPase activity of Rac1, Rap1, and Rab7, effectively reducing the infection of CHO-A24 cells [1].

Gancaonin I exhibits anti-BsFtsZ GTPase activities; it also shows significant inhibitory activity against B. subtilis, with a MIC value of 5 uM.

Cell-permeable version of dynamin inhibitory peptide, an inhibitor of the GTPase dynamin that competitively blocks binding of dynamin to amphiphysin, preventing endocytosis. Reduces NMDA receptor internalization.

6-Chloropurine riboside-5'-triphosphate serves as both an inhibitor and an activator in biochemical processes. It inhibits the RNA triphosphatase mRNA-capping enzyme subunit β (Cet1; IC50 = 2 µM for the GTPase activity of the S. cerevisiae enzyme), proving its efficacy against the enzyme responsible for the capping of mRNA molecules. Additionally, it acts as a phosphorylated derivative of 6-chloropurine riboside. This compound also activates the E. coli enzyme aspartate carbamoyltransferase (EC50 = 0.76 mM), demonstrating its versatility in modulating enzyme activities. It is instrumental in the synthesis of cytokinins with anticancer properties and a photoclickable form of ATP, highlighting its applications in biochemical synthesis and potential therapeutic uses.

Tetradecyltrimethylammonium bromide (MitMAB) is a Dynamin GTPase activity inhibitor and a cationic surfactant with asymmetrical structure.

8-Br-GTP, an analog of GTP, functions as both a competitive inhibitor of FtsZ polymerization and GTPase activity (with a K i value of 31.8 μM). Moreover, it is capable of facilitating nucleic acid modification.

FtsZ-IN-8, a potent inhibitor of FtsZ, both promotes FtsZ polymerization and inhibits its GTPase activity, leading to the inhibition of bacterial division and subsequent bacterial cell death. This compound exhibits bactericidal activity without significant induction of bacterial resistance and possesses rapid bactericidal properties. Additionally, FtsZ-IN-8 demonstrates low hemolytic activity and cytotoxicity towards mammalian cells [1].

FtsZ-IN-6 is a potent inhibitor of FtsZ, enhancing its polymerization while inhibiting its GTPase activity, thereby obstructing bacterial cell division and causing bacterial cell death. This compound exhibits bactericidal properties without significant induction of bacterial resistance and demonstrates rapid bactericidal effects. Moreover, FtsZ-IN-6 has low hemolytic activity and cytotoxicity towards mammalian cells [1].

Phox-I1 is a NOX2 inhibitor targeting the interactive site of p67phox with Rac GTPase.

CASIN (Pirl1-related Compound 2) is a specific inhibitor of GTPase Cdc42 (IC50: 2 uM).

Compound C108 is an inhibitor of GTPase-activating protein SH3 domain-binding protein 2 (G3BP2). Compound C108 can be used in studies about breast tumors and esophageal squamous cell carcinoma.

VA5 is an transamidase inhibitor by direct binding at the transamidase site. VA5 also inhibits GTP-binding activities. It interaction at the transamidase site locks the protein in the extended/open conformation to disorganize/inactivate the GTP binding/GT

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.

Sulfonadyn-47 is a dynamin inhibitor that effectively inhibits dynamin GTPase activity with an IC50 of 3.5 µM in cell-free assays. Additionally, it disrupts clathrin-mediated endocytosis in U2OS cells (IC50 = 27.3 µM) and impedes the depolarization-stimulated uptake of the synaptic vesicle endocytosis (SVE) marker FM4-64 in isolated rat brain synaptosomes (IC50 = 12.3 µM). Significantly, in vivo administration of sulfonadyn-47 at doses of 30 and 60 mg/kg demonstrates anticonvulsant properties in the 6 Hz corneal kindling mouse model of seizures.

ZCL278 is a selective Cdc42 GTPase inhibitor.

FtsZ-IN-7 is a potent inhibitor of FtsZ, enhancing FtsZ polymerization while inhibiting its GTPase activity, therefore disrupting bacterial cell division and culminating in bacterial cell death. It exhibits bactericidal effects without significant induction of bacterial resistance and demonstrates rapid antibacterial action. Additionally, FtsZ-IN-7 has minimal hemolytic activity and cytotoxicity towards mammalian cells [1].

FtsZ-IN-2 is an inhibitor of the bacterial cytokinin FtsZ and has an inhibitory effect on GTPase activity. ftsZ-IN-2 exhibited anti-staphylococcal effects with MIC values of 2 μg/ml for both MSSA and MRSA.

Narciclasine (Lycoricidinol), a natural product, modulates the Rho/Rho-kinase/LIM kinase/cofilin signaling pathway, greatly increasing GTPase RhoA activity.

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

HUN47990 is a bisphosphonate (BP) prodrug with antitumor activity. HUN47990 potently inhibits the in vitro growth of a variety of tumor cell lines, especially hematopoietic cell lines, at nanomolar concentrations. HUN47990 inhibited the prenylation of the RAP1A small GTPase signaling protein at concentrations as low as 1-10 nM. HUN47990 slowed the growth of human bladder cancer cells in an immunodeficient mouse model. HUN47990 is significantly more active than zoledronic acid, the most active FDA-approved BP, and a potential anti-cancer therapeutic. HUN47990 was first reported in ChemMedChem. 2016 Dec 16;11(24):2656-2663 (compound 7). This product has no formal name at the moment. For the convenience of communication, a temporary code name was therefore proposed according to MedKoo Chemical Nomenclature (see web page: https://www.medkoo.com/page/naming).

Clathrin-IN-2 is a potent inhibitor of clathrin-mediated endocytosis (CME), demonstrating an IC50 value of 2.3 μM. Additionally, it exhibits inhibitory effects on dynamin I GTPase, with an IC50 of 7.7 μM.

DRP1i27, a potent human dynamin-related protein 1 (Drp1) inhibitor, targets the GTPase site of Drp1, forming hydrogen bonds with Gln34 and Asp218. It mitigates Drp1-mediated mitochondrial fission in cell line models and offers protection against simulated ischemia-reperfusion injury.

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

Bragsin2 (6-methoxy-5-nitro-2-(trifluoromethyl)chromen-4-one) is a hydration-resistant cell penetrant, selective and non-competitive inhibitor of Afr guanine nucleotide exchange factor BRAG2 that inhibits Arf GTPase activation, with an IC50 of 3 μM. Bragsin2 binds at the interface between the pleckstrin homology domain of BRAG2 and the lipid bilayer, leading BRAG2 unable to activate lipidated Arf GTPase.