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G proteins (guanine nucleotide-binding proteins) are molecular switches that are regulated by GPCRs. When a ligand binds to the GPCR, the intracellular domain of the receptor activates a G protein. This activation results in the ability of a G protein to bind and hydrolyze GTP to GDP. Therefore, G proteins work along with GPCRs to translate extracellular signals into an intracellular events to produce changes in cellular processes. G proteins are known to regulate metabolic enzymes, ion channels, and parts of the cellular machinery that control transcription and development; G proteins have also been implicated in diseases such as cancer, diabetes, and depresssion. Sigma offers small molecules for G-protein research, including peptides, agonists, antagonists, inhibitors, toxins, phosphates, and GTP.

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SML0865 AA92593 ≥98% (HPLC) AA92593 is an opsinamide, a potent antagonist of melanopsin-mediated phototransduction with an IC50 of 665 nM in a Ca2+ flux assay in CHO cells expressing melanopsin (Opn4) and selectivity > 10 μM at 74 common biological targets. AA41612 is believed to act by competing for binding to melanopsin. AA41612 inhibited mouse pupillary light reflex and light aversion in vivo. AA92593 and similar compounds might be useful in alleviating the photophobia associated with migraine.
SML1720 ATI-2341 trifluoroacetate salt ≥95% (HPLC) ATI-2341 is a potent and selective allosteric agonist of chemokine CXC-type receptor 4 (CXCR4) that functions as a biased ligand, favoring Gαi activation over Gα13. ATI-2341 does not promote β-arrestin recruitment. ATI-2341 promotes the mobilization of PMNs and HSPCs in the peripheral circulation of both mice and monkeys.
SML0908 CCG-50014 ≥98% (HPLC) CCG-50014 is an inhibitor of Regulators of G protein Signaling (RGS) proteins RGS4 and RGS8, which bind to the Gα -subunits of activated heterotrimeric G-proteins, and accelerate the rate of GTP hydrolysis, acting as GTPase activating proteins. CCG-50014 irreversibly binds and destabilizes RGS proteins with no affect on Gα0, while blocking GTPase activity and Gα0-dependent translocation of RGS4 to the membrane.
C8772 Cholera filtrate lyophilized powder  
C8052 Cholera Toxin from Vibrio cholerae ~95% (SDS-PAGE), lyophilized powder Toxin consisting of an A subunit (27 kDa) surrounded by five B subunits (approximately 12 kDa each), which attach the toxin to ganglioside GM1 on the cell surface. The A subunit catalyzes ADP-ribosylation of the α-subunit of the stimulatory G protein (Gαs), reducing GTPase activity and activating the α-subunit. This activation of Gαs leads to an increase in the activity of adenylyl cyclase, resulting in increased levels of cAMP. Also ADP-ribosylates transducin in the eye rod outer segments, inactivating its GTPase activity. Cholera toxin has also been reported to ADP-ribosylate tubulin. Shown to be a potent mucosal vaccine adjuvant, inducing T helper cell type 2 responses by inhibiting the production of interleukin-12.
C8180 Cholera Toxin A Subunit from Vibrio cholerae lyophilized powder Catalyzes ADP-ribosylation of the α-subunit of G proteins, reducing GTPase activity and activating the α-subunit; also catalyzes ADP-ribosylation of cell membrane adenylyl cyclase
C9903 Cholera Toxin B subunit ≥95% (SDS-PAGE), lyophilized powder The cholera toxin B subunit is used for track tracing in neurological research, taking advantage of GM1 ganglioside binding and retrograde transport. Tissue culture cells treated with cholera toxin are not killed and tissues of animals do not become necrotic.
C167 Cholera Toxin B subunit solid The cholera toxin B subunit is used for track tracing in neurological research, taking advantage of GM1 ganglioside binding and retrograde transport. Tissue culture cells treated with cholera toxin are not killed and tissues of animals do not become necrotic.
C9972 Cholera Toxin B subunit biotin conjugate, lyophilized powder The cholera toxin B subunit is used for track tracing in neurological research, taking advantage of GM1 ganglioside binding and retrograde transport. Tissue culture cells treated with cholera toxin are not killed and tissues of animals do not become necrotic.
C1655 Cholera Toxin B subunit FITC conjugate, lyophilized powder The cholera toxin B subunit is used for track tracing in neurological research, taking advantage of GM1 ganglioside binding and retrograde transport. Tissue culture cells treated with cholera toxin are not killed and tissues of animals do not become necrotic.
SML0805 CID16020046 ≥98% (HPLC) CID16020046 is a potent and a selective GPR55 antagonist that inhibits GPR55-mediated ERK1/2 phosphorylation. CID16020046 inhibits LPI-induced Ca2+ signaling in HEK-GPR55 cells.
C3977 Clostridium difficile Toxin A lyophilized powder Clostridium difficile Toxin A and B, cation-dependent UDP-glucose glucosyltransferases, are cellular toxins that inactivate Rho (and Rho family small GTPases) through monoglucosylation of these family members. Effects of this monoglucosylation include disregulation of the actin cytoskeleton, cell rounding, cytotoxicity, and altered cellular signaling. Rho proteins are monoglucosylated by Toxin A and B using UDP-glucose as a cosubstrate. Rho, Rac and Cdc42 are included in the Rho subfamilies targeted by both toxins. Low molecular mass GTP-binding proteins that are not modified by Toxin A and B include Ras, Rab, Arf, or Ran subfamilies as well as heterotrimeric G proteins.
SML1154 Clostridium difficile Toxin A ≥95% (SDS-PAGE) Clostridium difficile Toxin A and B, cation-dependent UDP-glucose glucosyltransferases, are cellular toxins that inactivate Rho (and Rho family small GTPases) through monoglucosylation of these family members. Effects of this monoglucosylation include disregulation of the actin cytoskeleton, cell rounding, cytotoxicity, and altered cellular signaling. Rho proteins are monoglucosylated by Toxin A and B using UDP-glucose as a cosubstrate. Rho, Rac and Cdc42 are included in the Rho subfamilies targeted by both toxins. Low molecular mass GTP-binding proteins that are not modified by Toxin A and B include Ras, Rab, Arf, or Ran subfamilies as well as heterotrimeric G proteins.
C4102 Clostridium difficile Toxin B lyophilized powder Clostridium difficile Toxin A and B, cation-dependent UDP-glucose glucosyltransferases, are cellular toxins that inactivate Rho (and Rho family small GTPases) through monoglucosylation of these family members. Effects of this monoglucosylation include disregulation of the actin cytoskeleton, cell rounding, cytotoxicity, and altered cellular signaling. Rho proteins are monoglucosylated by Toxin A and B using UDP-glucose as a cosubstrate. Rho, Rac and Cdc42 are included in the Rho subfamilies targeted by both toxins. Low molecular mass GTP-binding proteins that are not modified by Toxin A and B include Ras, Rab, Arf, or Ran subfamilies as well as heterotrimeric G proteins.
Toxin B is 100-1,000-fold more cytotoxic than toxin A in inducing rounding-up of cells and destruction of the actin cytoskeleton.
SML1153 Clostridium difficile Toxin B ≥95% (SDS-PAGE) Clostridium difficile Toxin A and B, cation-dependent UDP-glucose glucosyltransferases, are cellular toxins that inactivate Rho (and Rho family small GTPases) through monoglucosylation of these family members. Effects of this monoglucosylation include disregulation of the actin cytoskeleton, cell rounding, cytotoxicity, and altered cellular signaling. Rho proteins are monoglucosylated by Toxin A and B using UDP-glucose as a cosubstrate. Rho, Rac and Cdc42 are included in the Rho subfamilies targeted by both toxins. Low molecular mass GTP-binding proteins that are not modified by Toxin A and B include Ras, Rab, Arf, or Ran subfamilies as well as heterotrimeric G proteins.
Toxin B is 100-1,000-fold more cytotoxic than toxin A in inducing rounding-up of cells and destruction of the actin cytoskeleton.
SML1215 Cuspin-1 ≥98% (HPLC) Cuspin-1 (Chemical Upregulator of SMN Protein-1) is an upregulator of the Survival of Motor Neuron protein (SMN), necessary for survival of motor neurons. SMN is decreased in the neurodegenerative disease Spinal Muscular Atrophy (SMA), an autosomal recessive disease caused by a genetic defect in the SMN1 gene. SMA is the second leading cause of neuromuscular disease, after Duchenne muscular dystrophy. Cuspin-1 increased SMN levels by 50-100% in SMA patient fibroblast cells accompanied by an increase in the phosphorylation of Erk, suggesting inbvolvement of the Ras-Raf-MEK cascade.
SML1481 FzM1 ≥98% (HPLC) FzM1 is an allosteric ligand of the Frizzled4 (Fz4) receptor and a Wnt/β-catenin pathway inhibitor, found by a screen for pharmacological chaperones for a misfolded mutant of the Frizzled4 (Fz4) receptor. FzM1 is believed to induce conformational changes in Fz4 by interacting with the third intracellular loop, ICL3, inhibiting binding of dishevelled (Dsh) and hampering the formation of the Fz4-Dsh complex that is necessary for β-catenin nuclear transport and ultimately transcription of TCF/LEF-regulated genes. FzM1 was tested on two tumor cell lines. U87MG glioblastoma cells acquired a more differentiated phenotype on application. FzM1 and FzM1alk also sped up the differentiation of Caco-2 cells. FzM1 has a log EC50 value of 5.74 for inhibition of Wnt antagonism.
SML0174 GPR35 Agonist, Compound 10 ≥98% (HPLC) GPR35 agonist Compound 10 is a GPR35 agonist the binds with higher affinity than other known agonists, such as kynurenic acid and zaprinast. Compound 10 was more potent than zaniprast (pEC50 = 5.3 vs 4.18) for recombinantly expressed human GPR35, and unlike zaprinast, is equipotent for human and rat GPR35
G9541 G Protein Antagonist ≥90% (HPLC) Inhibits the activation of Gαi or Gαo by M2 muscarinic cholinergic receptor.
SML0262 GSK575594A ≥98% (HPLC) GSK575594A is a selective agonist of human GPR55. It is specific for human over rodent GPR55. GSK575594A had no activity across a set of more than 200 validated molecular target assays from diverse classes including kinases, proteases and other enzymes, GPCRs, ion channels, nuclear receptors, and membrane transporters.
10220647001 GTP-γ-S Tetralithium salt  
G0635 Guanosine 5′-[β,γ-imido]triphosphate trisodium salt hydrate ≥85% (HPLC), powder Binds and irreversibly activates G proteins. Since a cycle of GTP binding, hydrolysis, and release is required for the initiation of protein translocation across the endoplasmic reticulum, this non-hydrolyzable GTP analog is often used in studies of protein synthesis.
G7637 Guanosine 5′-[β-thio]diphosphate trilithium salt ≥85% (HPLC), powder  
G8634 Guanosine 5′-[γ-thio]triphosphate tetralithium salt ≥75% (HPLC), powder GTP-γ-S is a non-hydrolyzable GTP analog, known for its role as a G-protein activator. It has recently been shown to protect proteins from proteolytic degradation, stimulate GLUT4 translocation in a tyrosine kinase-dependent manner, stimulate phospholipases and induce actin polymerization in vitro.
G5884 Guanosine 5′-triphosphate lithium salt ~95% (HPLC), powder GTP functions as a carrier of phosphates and pyrophosphates involved in channeling chemical energy into specific biosynthetic pathways. GTP activates the signal transducing G proteins which are involved in various cellular processes including proliferation, differentiation, and activation of several intracellular kinase cascades. Proliferation and apoptosis are regulated in part by the hydrolysis of GTP by small GTPases Ras and Rho. Another type of small GTPase, Rab, plays a role in the docking and fusion of vesicles and may also be involved in vesicle formation. In addition to its role in signal transduction, GTP also serves as an energy-rich precursor of mononucleotide units in the enzymatic biosynthesis of DNA and RNA.
G8877 Guanosine 5′-triphosphate sodium salt hydrate ≥95% (HPLC), powder GTP functions as a carrier of phosphates and pyrophosphates involved in channeling chemical energy into specific biosynthetic pathways. GTP activates the signal transducing G proteins which are involved in various cellular processes including proliferation, differentiation, and activation of several intracellular kinase cascades. Proliferation and apoptosis are regulated in part by the hydrolysis of GTP by small GTPases Ras and Rho. Another type of small GTPase, Rab, plays a role in the docking and fusion of vesicles and may also be involved in vesicle formation. In addition to its role in signal transduction, GTP also serves as an energy-rich precursor of mononucleotide units in the enzymatic biosynthesis of DNA and RNA.
E8656 Heat-Labile Enterotoxin, B subunit (LTB) from E. coli recombinant, expressed in Pichia pastoris, >90% (SDS-PAGE), lyophilized powder Enterotoxigenic Escherichia coli causes diarrhea through its heat-labile enterotoxin (LT). The LT is a periplasmic protein composed of one A subunit (LTA, 27 kDa) and five non-covalently associated B subunits (LTB, 11.6 kDa each) forming a ring-like pentamer. LTB has high affinity towards the toxin receptor ganglioside GM1, a glycosphingolipid found ubiquitously on the surface of mammalian cells. Ganglioside GM1 facilitates the delivery of the A subunit to the cytosol of the target cell resulting in persistent synthesis of cAMP and subsequently diarrhea. This characteristic makes LTB a good label for microglial cells (due to the enrichment of ganglioside GM1 on their cell surface). In addition, studies made mostly with animal models demonstrated that recombinant LTB could stimulate strong serum and mucosal immune responses against LT. Other studies have indicated that LTB could be used as a potent mucosal adjuvant.
SML0341 Importazole ≥98% (HPLC) Importazole is an inhibitor of importin-β transport receptors. During interphase, the transport receptor importin-β carries cargoes into the nucleus, where RanGTP releases them. Importazole somehow disrupts the importin/RAN interaction. Importazole is selective among other transporters. Compounds are imported into, but not out of, cells.
SML0405 JF5 hydrochloride ≥98% (HPLC) JF5 is an allosteric inhibitor of PAR1. The molecule binds to helix 8 of the receptor, directly interfering with receptor coupling to Gαq, but not Gα12. JF5 also inhibits α2A-adrenergic receptor and mPAR4 activity, but not hPAR4. JF5 blocks granule secretion from platelets activated with the PAR1 agonist SFLLRN (IC50 4 μM), but does not affect platelet activation by convulxin (GPVI agonist), PMA or A23187.
SML1624 JNJ-63533054 ≥98% (HPLC) JNJ-63533054 is a potent and selective agonist of the orphan receptor hGPR139, a GPCR receptor expressed in the brain in circumventricular regions of the habenula and septum. JNJ-63533054 has an EC50 value of 16 nM, crosses the blood-brain barrier, and is orally available.
M2816 Metastin (45-54) amide, human ≥95% Metastin is an endogenous ligand to G-protein-coupled orphan receptors such as OT7T175 (also known as AXOR12) and GPR54. Novel placenta-derived hormone. The amide form of metastin is found to be 3-10 times more active than the free acid form of metastin.
SML1340 ML193 trifluoroacetate ≥98% (HPLC) ML193 is a potent and selective piperadinyloxadiazolone antagonist for G protein-coupled receptor (GPCR) GPR55, a receptor for L-α-lysophosphatidylinosi
SML0423 ML194 ≥98% (HPLC) ML194 (CID9581011) is an antagonist of GPR35, a GPRC receptor expressed in nervous system tissue, in the GI tract particularly in pancreas and small intestine, followed by colon, spleen, and immune cells, and also expressed in gastric carcinomas. GPR35 is being investigated for potential therapeutic importance in a variety of areas including pain, hypertension, cancer, diabetes and asthma. ML194 is more membrane penetrant and more potent than earlier synthetic antagonists, with an IC50 of 160nM. ML194 was also found to rescue the cell-surface expression of mutant GPR35 receptors, likely acting as a pharmacological chaperone to alter the misfolded receptor structure.
SML1482 Ogerin ≥98% (HPLC) Ogerin is a selective positive allosteric modulator of an orphan GPCR, GPR68, also known as Ovarian cancer G-protein coupled receptor 1 (OGR1). GPR68 is one of the proton or pH-sensing GPCRs that sense extracellular H(+). Ogerin potently potentiated proton-mediated GPR68-Gs signaling. Ogerin was not active in GPR68 knockout mice, but was found to suppress recall in fear conditioning in wild-type mice, showing an unexpected effect of GPR68 on learning and memory.
SML1483 Ogerin negative control ≥98% (HPLC) Ogerin negative control is a structurally similar analog of ogerin (catalog no. SML1482). Ogerin is a selective positive allosteric modulator of an orphan GPCR, GPR68, also known as Ovarian cancer G-protein coupled receptor 1 (OGR1). GPR68 is one of the proton or pH-sensing GPCRs that sense extracellular H(+). Ogerin potently potentiated proton-mediated GPR68-Gs signaling. The meta-analog is inactive and serves as a negative control.
P7208 Pertussis toxin from Bordetella pertussis lyophilized powder Pertussis toxin catalyzes the ADP-ribosylation of the α subunits of the heterotrimeric guanine nucleotide regulatory proteins Gi, Go, and Gt. This prevents the G protein heterotrimers from interacting with receptors, thus blocking their coupling and activation. Since the Gα subunits remain in their GDP-bound, inactive state, they are unable to inactivate adenylyl cyclase or open K+ channels.
P2980 Pertussis toxin from Bordetella pertussis buffered aqueous glycerol solution Pertussis toxin catalyzes the ADP-ribosylation of the α subunits of the heterotrimeric guanine nucleotide regulatory proteins Gi, Go, and Gt. This prevents the G protein heterotrimers from interacting with receptors, thus blocking their coupling and activation. Since the Gα subunits remain in their GDP-bound, inactive state, they are unable to inactivate adenylyl cyclase or open K+ channels.
P159 Pertussis toxin B oligomer solid Subunit of pertussis toxin responsible for binding to cell surfaces; stimulates both platelet aggregation and cytosolic Ca2+ level elevation, may also activate phospholipase C; isolated from B pertussis strain 165.
SML0800 Rimonabant hydrochloride ≥98% (HPLC) Rimonabant hydrochloride (SR-141716A) is a potent and selective CB1 cannabinoid inverse agonist/antagonist with a Ki of 1.6 nM, minimal affinity for CB2, and and some GPR55 agonist activity. Rimonabant was developed as an anti-obesity drug because of its appetite suppressant activity, but was taken off the market because of side effects of depression and anxiety.
S4063 SCH-202676 hydrobromide 98% Allosteric agonist and antagonist of G-protein coupled receptors (GPCRs).
SCH-202676 inhibits the binding of both agonists and antagonists to G protein-coupled receptors. It also inhibits human μ-, δ-, and κ-opioid, α- and β-adrenergic, muscarinic M1 and M2, and dopaminergic D1 and D2 receptors. Some reports indicates thiol modification as the mechanism of inhibition rather than allosteric modulation.
SML0562 Shiga Toxin 1, B subunit recombinant, expressed in E. coli, ≥95% (SDS-PAGE) The Shiga toxins are a family of related protein toxins secreted by certain types of bacteria. Shiga toxin (Stx) is produced by Shigella dysenteriae, whereas the Shiga-like toxins, Stx1 and Stx2, with a few known isoforms, are secreted by specific strains of Escherichia coli named Shiga-toxin-producing E. coli (STEC) such as E. coli O157:H7, which causes bloody diarrhea and hemorrhagic colitis in humans, sometimes resulting in fatal systemic complications.

Stx1 is identical to Stx, while the Stx2 isoforms share less sequence similarity with Stx (~60%) and are immunologically distinct. In spite of the differences in their amino acid sequence, all Stx isoforms share the same overall toxin structure and mechanism of action.

Shiga toxins consist of two polypeptides: An A chain and a B chain non-covalently associated with an apparent stoichiometry of one A and five B chains, to form the holotoxin. The catalytic A subunit has a RNA N-glycosidase activity that inhibits eukaryotic protein synthesis. The B subunits form a pentamer that recognizes and binds to the functional cell-surface receptor globotriaosylceramide [Gb3; Gala(1-4)-Galb(1-4)-Glcb1-ceramide]. Gb3 is overexpressed in membranes of numerous tumor cells, therefore STxB binding to Gb3 receptors may be useful for cell-specific vectorization, labeling and imaging purposes.
SML0655 Shiga toxin 1, B subunit, HIS-tagged recombinant, expressed in E. coli, ≥95% (SDS-PAGE) The Shiga toxins are a family of related protein toxins secreted by certain types of bacteria. Shiga toxin (Stx) is produced by Shigella dysenteriae; whereas, the Shiga-like toxins, Stx1 and Stx2, with a few known isoforms, are secreted by specific strains of Escherichia coli named Shiga-toxin-producing E. coli (STEC), such as E. coli O157:H7, which causes bloody diarrhea and hemorrhagic colitis in humans, sometimes resulting in fatal systemic complications.

Stx1 is identical to Stx, while the Stx2 isoforms share less sequence similarity with Stx (∼60%) and are immunologically distinct. In spite of the differences in their amino acid sequence, all Stx isoforms share the same overall toxin structure and mechanism of action.

Shiga toxins consists of two polypeptides. An A chain and a B chain non-covalently associate with an apparent stoichiometry of one A and five B chains to form the holotoxin. The catalytic A subunit has
RNA N-glycosidase activity that inhibits eukaryotic protein synthesis. The B subunits form a pentamer, which recognizes and binds to the functional cell-surface receptor globotriaosylceramide [Gb3; Gala(1-4)-Galb(1-4)-Glcb1-ceramide]. Gb3 is overexpressed in membranes of numerous tumor cells, therefore STxB binding to Gb3 receptors may be useful for cell-specific vectorization, labeling, and imaging purposes.
S3131 Sulindac sulfide ≥98% (HPLC), solid Sulindac sulfide is a non-steroidal anti-inflammatory compound with a preference for COX-1; it is an inhibitor of Ras activation of Raf-1. It impairs nucleotide exchange on Ras by CDC25 and accelerates Ras hydrolysis of GTP by p120GAP. It is an active metabolite of sulindac. It is also shown to inhibit growth and induce apoptosis in human prostate cancer cells through a COX-1 and COX-2 independent mechanism. Sulindac sulfide is an analgesic that has antiproliferative and apoptotic effects. It inhibits the expression and activity of cyclooxygenase-2 in human colon cancer cells and reduces tumor burden in adenomatous polyposis patients.
S2671 Suramin sodium salt ≥99% (TLC) Suramin is a polysulfonated naphthylurea anticancer agent that inhibits tumor cell proliferation. It inhibits the activity of topoisomerase II by blocking the binding of the enzyme to DNA. It′s antiangiogenic activity may be related to its ability to bind to and inhibit the activity of several growth factors, including FGFa, FGFb, and PGDF. It uncouples G-proteins from receptors. It is an broad spectrum antagonist at P2X and P2Y purinergic receptors. Suramin has well documented antiprotozoal and anthelmintic activity.
SML1773 TYFAVLM trifluoroacetate salt ≥98% (HPLC) TYFAVLM/P7, a synthetic peptides comprising adhesion GPR56 β-strand-13 stalk, is a potent and selective agonist of GPR56. TYFAVLM activates GPR56 in cells.
SML1699 (R)-ZINC-3573 ≥98% (HPLC) (R)-ZINC-3573 is a selective agonist probe of the orphan receptor Mas-related G-protein coupled receptor member X2 (MRGPRX2), a G-protein coupled receptor (GPCR) selectively expressed in mast cells and dorsal root and trigeminal ganglia primary sensory neurons of primates. Lack of selective and potent probes has made it difficult to determine MRGPRX2 funtion. (R)-ZINC-3573 was shown to be a potent and selective agonist with an EC50 value of 760 nM for MRGPRX2 and little activity for MRGPRX1 or over 350 other GPCRs and 97 kinases tested. (R)-ZINC-3573 activates endogenous MRGPRX2 expressed in a human mast cell line and induced degranulation and calcium release. (S)-ZINC-3573 is inactive and can be used as a control.
SML1700 (S)-ZINC-3573 ≥98% (HPLC) (S)-ZINC-3573 is an inactive control probe for (R)-ZINC-3573, which is a selective agonist probe of the GPCR orphan receptor MRGPRX2.