目录号 | 产品详情 | 靶点 | |
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T70538 | |||
PD-85639 is a voltage-gated sodium (Na+) channel blocker (75% in 10 min & >95% in 25 min blockage of Na+ current by 25 μM PD85,639; whole-cell patch clamp using primary rat brain neurons) that is shown to target rat brain Nav1.2 with simultaneous high- and low-affinity modes of binding (EC50 = 56 nM/40% & 20 μM/60% at pH 9.0, 5 nM/28% & 3 μM/72% at pH 7.4, against 2 nM [3H]-PD85,639 for binding rat brain synaptosomes; EC50 = 17 nM/39% & 10 μM/61% using at pH 9.0 using rat brain synaptosome membranes) and a fast kinetic (t1/2 = 1.2 at 4°C, <0.5 min at 25°C), competitive against the local anesthetic Na+ channel blockers tetracaine, bupivacaine, and mepivacaine, as well as Na+ channel activators veratridine and batrachotoxin (K1 = 0.26 μM against 5 nM [3H]-BTX for binding rat neocrotical membranes). | |||
T83731 | |||
Tat-CBD3是一种抑制N型电压门控钙通道Cav2.2与collapsin response mediator protein 2 (CRMP2)之间的蛋白质-蛋白质相互作用的抑制剂。它还能抑制CRMP2与NMDA受体NR2B亚单位之间的蛋白质-蛋白质相互作用。在无细胞实验中,Tat-CBD3 (10 µM)能将Cav2.2-CRMP2相互作用抑制43%,并在免疫共沉淀实验中抑制NMDA受体NR2B亚单位-CRMP2相互作用。它能在初级大鼠背根神经节 (DRG) 神经元中减少约60%的电压诱导钙电流,并在初级大鼠海马神经元中减少谷氨酸诱导的胞内钙水平增加。Tat-CBD3 (20 mg/kg)在大鼠中脑动脉闭塞 (MCAO) 引发的脑缺血模型中减少梗死体积。鞘内给药Tat-CBD3 (20 µg/5 µl)可防止大鼠卡拉胶诱导的热敏感性。 | |||
T83732 | |||
Tat-CBD3A6K是一种肽类化合物,为N型电压门控钙通道Cav2.2以及collapsin response mediator protein 2 (CRMP2) 蛋白-蛋白相互作用抑制剂Tat-CBD3的衍生物。Tat-CBD3A6K (10 mg/kg) 能够阻止由d4T (stavudine)引发的大鼠抗逆转录病毒神经病痛模型中爪撤回阈值的下降,并减少同一大鼠分离的背根神经节(DRG)神经元的动作电位数量。通过硬膜途径给予Tat-CBD3A6K (30 µM/animal) 能够减少由萜类生物碱辣椒素引发的大鼠硬脑膜血流增加。 | |||
T35426 | |||
β-Defensin-1 is a peptide with antimicrobial properties that protects the skin and mucosal membranes of the respiratory, genitourinary, and gastrointestinal tracts.1It inhibits the growth ofB. adolescentis,L. acidophilus,B. breve,B. vulgatus,L. fermentum,B. longum, andS. thermophilusin an antimicrobial radial diffusion assay.2β-Defensin-1 also inhibits the growth of periodontopathogenic and cariogenic bacteria, includingP. gingivalisandS. salivarius, and of susceptibleM. tuberculosisH37Rv but not of resistantM. tuberculosisRM22 when used at a concentration of 128 μg/ml.3,4It blocks human and mouse Kv1.3 voltage-gated potassium channels (IC50s = 11.8 and 13.2 μM, respectively).5Overexpression of β-defensin-1 in the human oral squamous cell carcinoma (OSCC) cell lines HSC-3, UM-1, and SCC-9 increases migration and invasion but not proliferation.6 1.Lehrer, R.I.Primate defensinsNat. Rev. Microbiol.2(9)727-738(2004) 2.Schroeder, B.O., Ehmann, D., Precht, J.C., et al.Paneth cell α-defensin 6 (HD-6) is an antimicrobial peptideMucosal Immunol.8(3)661-671(2015) 3.Ouhara, K., Komatsuzawa, H., Yamada, S., et al.Susceptibilities of periodontopathogenic and cariogenic bacteria to antibacterial peptides, β-defensins and LL37, produced by human epithelial cellsJ. Antimicrob. Chemother.55(6)888-896(2005) 4.Fattorini, L., Gennaro, R., Zanetti, M., et al.In vitro activity of protegrin-1 and beta-defensin-1, alone and in combination with isoniazid, against Mycobacterium tuberculosisPeptides25(7)1075-1077(2004) 5.Feng, J., Xie, Z., Yang, W., et al.Human beta-defensin 1, a new animal toxin-like blocker of potassium channelToxicon113(2016) 6.Han, Q., Wang, R., Sun, C., et al.Human beta-defensin-1 suppresses tumor migration and invasion and is an independent predictor for survival of oral squamous cell carcinoma patientsPLoS One9(3)e91867(2014) | |||
T83662 | |||
2,3-dinor-8-iso Prostaglandin F1α(2,3-dinor-8-iso PGF1α)是一种异前列腺素和花生四烯酸的活性代谢物,也是血小板聚集抑制剂8-iso PGF2α的产物。它通过花生四烯酸的非酶促自由基过氧化作用形成。2,3-dinor-8-iso PGF1α在孤立的猪视网膜和大脑微血管中引起血管收缩(EC50s分别为12.8和18.5 nM),但在31 µM的浓度下使用时不会引起孤立的大鼠主动脉环的收缩。在1 µM的浓度下使用时,它能增加孤立的猪大脑切片中的血栓素B2(TXB2)水平,这一效应可以通过血栓素A合成酶抑制剂CGS 12970、电压门控钙通道抑制剂SKF 96365或烟碱型乙酰胆碱受体(nAChR)拮抗剂α-conotoxin来逆转。 | |||
T83739 | |||
Myr-Tat-CBD3是一种抑制N型电压门控钙通道Cav2.2与collapsin response mediator protein 2 (CRMP2)之间的蛋白-蛋白相互作用的抑制剂。在10 µM的浓度下,该化合物能够约81%地抑制Cav2.2-CRMP2相互作用,并在大鼠初级背根神经节(DRG)神经元中抑制钾诱导的钙流入(IC50约为2.8 µM)。在20 µM的浓度下,Myr-Tat-CBD3能抑制钙电流,但不影响钠电流,在初级DRG神经元中表现出这种特性。经过脊髓内给药,myr-Tat-CBD3(20 µg/5 µl)能够防止大鼠脚掌撤回潜伏期因carrageenan注射而减少。此外,Myr-Tat-CBD3减少大鼠因线索引起的寻求可卡因行为的复发。 | |||
T36803 | |||
Photoswitchable Kv channel blocker (IC50 values are 2 and 64 μM at 500 nm and 380 nm respectively). Switches conformation from cis to trans at 500 nm and trans to cis at 380 nm. Exhibits minimal activity at Nav1.2 and L-type Ca2+ channels. Stimulates action potential firing of hippocampal neurons in vitro at 500 nm and restores visual responsiveness in blind mice at 380 nm. Fortin et al (2008) Photochemical control of endogenous ion channels and cellular excitability. Nat.Methods 5 331 PMID:18311146 |Polosukhina et al (2012) Photochemical restoration of visual responses in blind mice. Neuron 75 271 PMID:22841312 |Banghart et al (2009) Photochromic blockers of voltage-gated potassium channels. Angew.Chem.Int.Ed. 48 9097 PMID:19882609 | |||
T36805 | |||
TPC2-A1-N is a novel, lipophilic, membrane permeable isoform-selective small molecule agonist of two-pore channel 2 (TPC2). TPC2-A1-N plays its role by mimicking the physiological actions of NAADP and PI(3,5)P2 through independent binding sites. TPC2-A1-N has inverse effects on key lysosomal activities and increases the pH in the lysosomal lumen in a TPC2-dependent manner[1]. | |||
T36806 | |||
TPC2-A1-P is a powerful and membrane permeable agonist of two pore channel 2 (TPC2) with an EC50 of 10.5 μM. TPC2-A1-P plays its role by mimicking the physiological actions of PI(3,5)P2. TPC2-A1-P also shows higher potency to induce Na2+ mobilisation from TPC2 than TPC-A1-N . TPC2-A1-P can be used to probe different functions of TPC2 channels in intact cells[1][2][3]. Two-pore channels (TPC1-3) are ancient members of the voltage-gated ion channel superfamily. TPCs are expressed throughout the endo-lysosomal system and regulates the trafficking of various cargoes[1].TPC2 can mediate different physiological and possibly pathophysiological effects depending on how it is activated. The ion selectivity of TPC2 is not fixed but rather agonist-dependent. TPC2 is a unique example of an ion channel that conducts different ions in response to different activating ligands[1].TPC2-A1-P (10 μM) reproducibly evokes Ca2+ signals, and TPC2-A1-P response reachs its plateau slower than TPC2-A1-N . The EC50 in full concentration-effect relationships for the plateau response is 10.5 μM for TPC2-A1-P in a cell line stably expressing TPC2L11A/L12A.TPC2-A1-P (10-30 μM) induces Ca2+ signals in Hela cells expressing TPC2 in the presence but not absence of extracellular Ca2+. However, the responses are smaller and delayed compared to TPC2-A1-N , consistent with the results obtained in cells stably expressing TPC2L11A/L12A. TPC2-A1-P fails to induce Ca2+ signals in cells expressing ’pore-dead’ TPC2L11A/L12A/L265P and also fails to evoke Ca2+ signals in cells expressing human TRPML1 re-routed to the plasma membrane (TRPML1δNC)[1].In endo-lysosomal patch-clamp experiments, TPC2-A1-P (10 μM) evokes currents in endo-lysosomes isolated from cells expressing TPC2 and TPC2M484L, the currents evoked by TPC2-A1-P are significantly larger than those evoked by TPC2-A1-N in both wild-type and gain-of-function variant,and exhibits an EC50 value of 0.6 μM for TPC2-A1-P[1]. [1]. Susanne Gerndt, et al. Agonist-mediated switching of ion selectivity in TPC2 differentially promotes lysosomal function. Elife. 2020 Mar 16;9:e54712. [2]. Gerndt S, et al. Discovery of lipophilic two-pore channel agonists. FEBS J. 2020;287(24):5284-5293. [3]. Xuhui Jin, et al. Targeting Two-Pore Channels: Current Progress and Future Challenges. Trends Pharmacol Sci. 2020 Aug;41(8):582-594. |
目录号 | 产品名/同用名 | 种属 | 表达系统 | ||
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TMPY-03697 | SCN2B Protein, Human, Recombinant (His) | Human | HEK293 | ||
SCN2B plays a key role in the assembly, expression, and functional modulation of the heterotrimeric complex of the sodium channel. Voltage-gated sodium channels (NaV) are composed of one pore-forming alpha-subunit, which may be associated with either one or more beta-subunits. Alpha-subunits are composed for four homologous domains, each of which contains six transmembrane segments. They are responsible for action potential initiation and propagation in excitable cells, including nerve, muscle, and neuroendocrine cell types. SCN2B causes an increase in the plasma membrane surface area and in its folding into microvilli. SCN2B also interacts with TNR and may play a crucial role in clustering and regulation of activity of sodium channels at nodes of ranvier.
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TMPY-03183 | SCN2B Protein, Human, Recombinant (hFc) | Human | HEK293 | ||
SCN2B plays a key role in the assembly, expression, and functional modulation of the heterotrimeric complex of the sodium channel. Voltage-gated sodium channels (NaV) are composed of one pore-forming alpha-subunit, which may be associated with either one or more beta-subunits. Alpha-subunits are composed for four homologous domains, each of which contains six transmembrane segments. They are responsible for action potential initiation and propagation in excitable cells, including nerve, muscle, and neuroendocrine cell types. SCN2B causes an increase in the plasma membrane surface area and in its folding into microvilli. SCN2B also interacts with TNR and may play a crucial role in clustering and regulation of activity of sodium channels at nodes of ranvier.
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TMPY-02976 | SCN3B Protein, Human, Recombinant (His) | Human | HEK293 | ||
SCN3B (sodium channel, voltage-gated, type III, beta, human IgG1-Fc chimera) belongs to the sodium channel auxiliary subunit SCN3B family. It contains 1 Ig-like C2-type (immunoglobulin-like) domain. Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit and one or more regulatory beta subunits. They are responsible for the generation and propagation of action potentials in neurons and muscle. SCN3B gene encodes one member of the sodium channel beta subunit gene family, and influences the inactivation kinetics of the sodium channel. Two alternatively spliced variants, encoding the same protein, have been identified. Defects in SCN3B are the cause of Brugada syndrome type 7. A tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram. It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs (called ventricular fibrillation), the individual will faint and may die in a few minutes if the heart is not reset.
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TMPY-02722 | SCN3B Protein, Human, Recombinant (hFc) | Human | HEK293 | ||
SCN3B (sodium channel, voltage-gated, type III, beta, human IgG1-Fc chimera) belongs to the sodium channel auxiliary subunit SCN3B family. It contains 1 Ig-like C2-type (immunoglobulin-like) domain. Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit and one or more regulatory beta subunits. They are responsible for the generation and propagation of action potentials in neurons and muscle. SCN3B gene encodes one member of the sodium channel beta subunit gene family, and influences the inactivation kinetics of the sodium channel. Two alternatively spliced variants, encoding the same protein, have been identified. Defects in SCN3B are the cause of Brugada syndrome type 7. A tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram. It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs (called ventricular fibrillation), the individual will faint and may die in a few minutes if the heart is not reset.
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TMPH-02308 | CACNA2D1 Protein, Human, Recombinant (His & SUMO) | Human | E. coli | ||
The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Plays an important role in excitation-contraction coupling.
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TMPH-00780 | CACNA1C Protein, Guinea Pig, Recombinant (His) | Guinea pig | in vitro E. coli expression system | ||
Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents. Mediates influx of calcium ions into the cytoplasm, and thereby triggers calcium release from the sarcoplasm. Plays an important role in excitation-contraction coupling in the heart. Required for normal heart development and normal regulation of heart rhythm. Required for normal contraction of smooth muscle cells in blood vessels and in the intestine. Essential for normal blood pressure regulation via its role in the contraction of arterial smooth muscle cells. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group.
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TMPY-02245 | SNAP-25 Protein, Human, Recombinant (His) | Human | E. coli | ||
Synaptosomal-associated protein 25, also known as Super protein, Synaptosomal-associated 25 kDa protein, SNAP25 and SNAP, is a cytoplasm and cell membrane protein that belongs to the SNAP-25 family. SNAP25 / SUP contains 2 t-SNARE coiled-coil homology domains. SNAP25 / SUP is a membrane bound protein anchored to the cytosolic face of membranes via palmitoyl side chains in the middle of the molecule. SNAP25 / SUP protein is a component of the SNARE complex, which is proposed to account for the specificity of membrane fusion and to directly execute fusion by forming a tight complex that brings the synaptic vesicle and plasma membranes together. SNAP25 / SUP is a Q-SNARE protein contributing two α-helices in the formation of the exocytotic fusion complex in neurons where it assembles with syntaxin-1 and synaptobrevin. SNAP25 / SUP is involved in the molecular regulation of neurotransmitter release. It may play an important role in the synaptic function of specific neuronal systems. SNAP25 / SUP associates with proteins involved in vesicle docking and membrane fusion. SNAP25 / SUP regulates plasma membrane recycling through its interaction with CENPF. SNAP25 / SUP inhibits P/Q- and L-type voltage-gated calcium channels located presynaptically and interacts with the synaptotagmin C2B domain in Ca2+-independent fashion. In glutamatergic synapses SNAP25 / SUP decreases the Ca2+ responsiveness, while it is naturally absent in GABAergic synapses.
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TMPH-01394 | GRIN1 Protein, Human, Recombinant (His) | Human | E. coli | ||
Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+). Sensitivity to glutamate and channel kinetics depend on the subunit composition.
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TMPY-03615 | CSEN Protein, Human, Recombinant (His) | Human | E. coli | ||
KCNIP3 (Potassium Voltage-Gated Channel Interacting Protein 3, also known as CSEN) is a Protein Coding gene. CSEN is a member of the family of voltage-gated potassium (Kv) channel-interacting proteins, which belong to the recoverin branch of the EF-hand superfamily. Members of this family are integral subunit components of native Kv4 channel complexes that may regulate A-type currents, and hence neuronal excitability, in response to changes in intracellular calcium. CSEN also functions as a calcium-regulated transcriptional repressor and interacts with presenilins. CSEN binds to the DRE element of genes including PDYN and FOS. CSEN is broadly expressed in the brain, thyroid, and other tissues. Diseases associated with KCNIP3 include Alzheimer's Disease and Niemann-Pick Disease, Type C2.
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TMPH-03751 | CYBB Protein, Human, Recombinant (His) | Human | E. coli | ||
Critical component of the membrane-bound oxidase of phagocytes that generates superoxide. It is the terminal component of a respiratory chain that transfers single electrons from cytoplasmic NADPH across the plasma membrane to molecular oxygen on the exterior. Also functions as a voltage-gated proton channel that mediates the H(+) currents of resting phagocytes. It participates in the regulation of cellular pH and is blocked by zinc.
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TMPH-01744 | NOX1 Protein, Human, Recombinant (His) | Human | in vitro E. coli expression system | ||
NOH-1S is a voltage-gated proton channel that mediates the H(+) currents of resting phagocytes and other tissues. It participates in the regulation of cellular pH and is blocked by zinc. NOH-1L is a pyridine nucleotide-dependent oxidoreductase that generates superoxide and might conduct H(+) ions as part of its electron transport mechanism, whereas NOH-1S does not contain an electron transport chain.
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TMPH-01891 | KCNE2 Protein, Human, Recombinant (His) | Human | in vitro E. coli expression system | ||
Ancillary protein that assembles as a beta subunit with a voltage-gated potassium channel complex of pore-forming alpha subunits. Modulates the gating kinetics and enhances stability of the channel complex. Assembled with KCNB1 modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1. Associated with KCNH2/HERG is proposed to form the rapidly activating component of the delayed rectifying potassium current in heart (IKr). May associate with KCNQ2 and/or KCNQ3 and modulate the native M-type current. May associate with HCN1 and HCN2 and increase potassium current. Interacts with KCNQ1; forms a heterooligomer complex leading to currents with an apparently instantaneous activation, a rapid deactivation process and a linear current-voltage relationship and decreases the amplitude of the outward current.
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TMPH-01609 | LGI1 Protein, Human, Recombinant (His & Myc) | Human | E. coli | ||
Regulates voltage-gated potassium channels assembled from KCNA1, KCNA4 and KCNAB1. It slows down channel inactivation by precluding channel closure mediated by the KCNAB1 subunit. Ligand for ADAM22 that positively regulates synaptic transmission mediated by AMPA-type glutamate receptors. Plays a role in suppressing the production of MMP1/3 through the phosphatidylinositol 3-kinase/ERK pathway. May play a role in the control of neuroblastoma cell survival.
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TMPH-00056 | Delta-AITX-Avd1c Protein, Anemonia sulcata, Recombinant (His) | Anemonia sulcata | Yeast | ||
Binds specifically to voltage-gated sodium channels (Nav) (site 3), thereby delaying their inactivation. Has a strong effect on crustaceans and insects (DmNav1) and a weaker effect on mammals. This toxin is highly potent at mammalian Nav1.1/SCN1A (EC(50)=6.01 nM) and Nav1.2/SCN2A (EC(50)=7.88 nM). It has also great activity on Nav1.5/SCN5A (EC(50)=49.05 nM), Nav1.4/SCN4A (EC(50)=109.49 nM) and Nav1.6/SCN8A (EC(50)=about 180 nM) and is less potent on Nav1.3/SCN3A (EC(50)=759.22 nM) (when measured as the increase in the slow component).
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TMPJ-00587 | NRCAM Protein, Human, Recombinant (hFc) | Human | Human Cells | ||
Neuronal cell adhesion molecule(NRCAM) is a single-pass type I membrane protein ,containing 5 fibronectin type-III domains and 6 Ig-like C2-type (immunoglobulin-like) domains.It belongs to the immunoglobulin superfamily. NrCAM is engaged in such biological processes as axonal fasciculation, cell-cell adhesion, central nervous system development, clustering of voltage-gated sodium channels, neuron migration, positive regulation of neuron differentiation, regulation of axon extension, and synaptogenesis. It also may play a role in the molecular assembly of the nodes of Ranvier. NrCAM effects are also linked with different recognition processes and signal transduction pathways regulating cell differentiation, proliferation, or migration
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TMPY-02737 | DPP2 Protein, Mouse, Recombinant (His) | Mouse | HEK293 | ||
DPP7 (dipeptidylpeptidase 7), also known as DPPII and DPP2, is a post-proline cleaving aminopeptidase expressed in quiescent lymphocytes. Dipeptidyl peptidases (DPPs) have post-proline dipeptidyl aminopeptidase activity, cleaving Xaa-Pro dipeptides from the N-termini of proteins. DPPs mediate regulatory activity of their substrates and have been linked to a variety of diseases including type 2 diabetes, obesity and cancer. DPPs can bind specific voltage-gated potassium channels and alter their expression and biophysical properties and may also influence T cells. DPP proteins include DPRP1, DPRP2, DPP3, DPP7, DPP10, DPPX and CD26. It localizes to lysosomes. DPP7 localizes to lysosomes and exists as a homodimer via its leucine zipper motif and is involved in the degradation of oligopeptides. In response to calcium release, it can be secreted in its active form. It is essential for lymphocyte survival, as the inhibition of DPP7 results in quiescent cell apoptosis.
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TMPY-00777 | DPP2 Protein, Human, Recombinant (His) | Human | HEK293 | ||
DPP7 (dipeptidylpeptidase 7), also known as DPPII and DPP2, is a post-proline cleaving aminopeptidase expressed in quiescent lymphocytes. Dipeptidyl peptidases (DPPs) have post-proline dipeptidyl aminopeptidase activity, cleaving Xaa-Pro dipeptides from the N-termini of proteins. DPPs mediate regulatory activity of their substrates and have been linked to a variety of diseases including type 2 diabetes, obesity and cancer. DPPs can bind specific voltage-gated potassium channels and alter their expression and biophysical properties and may also influence T cells. DPP proteins include DPRP1, DPRP2, DPP3, DPP7, DPP10, DPPX and CD26. It localizes to lysosomes. DPP7 localizes to lysosomes and exists as a homodimer via its leucine zipper motif and is involved in the degradation of oligopeptides. In response to calcium release, it can be secreted in its active form. It is essential for lymphocyte survival, as the inhibition of DPP7 results in quiescent cell apoptosis.
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TMPH-00818 | Delta-theraphotoxin-Hm1a Protein, Heteroscodra maculata, Recombinant (His & Myc & SUMO) | Heteroscodra maculata | E. coli | ||
Gating-modifier toxin that potently inhibits inactivation of the mammalian Nav1.1/SCN1A sodium channel (EC(50)=38 nM). Also moderately inhibits inactivation of Nav1.2/SCN2A (EC(50)=236 nM) and Nav1.3/SCN3A (EC(50)=220 nM) when the channels are expressed in oocytes without the beta-1 auxiliary subunit. Does not inhibit inactivation of Nav1.2/SCN2A when the channel is coexpressed with the beta-1 auxiliary subunit. When tested on Nav1.1/SCN1A channel, it enhances peak current amplitude and potently delays channel inactivation in a dose-dependent manner, leading to a large sustained current. It has no effect on the voltage-dependence of steady-state activation, and induces a depolarizing shift in the voltage dependence of inactivation. In addition, it does not modify the recovery from fast inactivation in Nav1.1/SCN1A. The binding affinity and subtype selectivity of the toxin towards Nav1.1/SCN1A channel is determined by residues within both the S1-S2 and S3-S4 loops of the domain IV voltage sensor of the channel. This toxin also weakly inhibits several subtypes of voltage-gated potassium channels. It moderately blocks Kv2.1/KCNB1 (23% inhibition at 100 nM), Kv2.2/KCNB2 (19.7% at 100 nM and 51% at 300 nM), Kv4.1/KCND1 (IC(50)=280 nM), Kv4.2/KCND2 (39% at 300 nM) and Kv4.3/KCND3 (43% at 300 nM). In vivo, intracerebroventricular injection into mice elicits convulsions, spasms, tremors and rapid death. When injected into mouse hindpaw, the toxin elicits an immediate and robust response to pain. However, intraplantar injection of toxin does not cause neurogenic inflammation or alter sensitivity to heat, indicative of a modality-specific effect on mechanosensitive neurons. In Dravet syndrome mice model, intracerebroventricular infusion of this peptide rescues mice from seizures and premature death.
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TMPY-01854 | DPP10 Protein, Human, Recombinant (His) | Human | HEK293 | ||
Inactive dipeptidyl peptidase 1, also known as Dipeptidyl peptidase IV-related protein 3, Dipeptidyl peptidase X, Dipeptidyl peptidase-like protein 2, DPRP-3, DPL2 and DPP1, is a single-pass type II membrane protein which belongs to thepeptidase S9B family.DPPIV subfamily. It may modulate cell surface expression and activity of the potassium channels KCND1 and KCND2. DPP1 / DPRP3 has no detectable protease activity, most likely due to the absence of the conserved serine residue normally present in the catalytic domain of serine proteases. However, it does bind specific voltage-gated potassium channels and alters their expression and biophysical properties. Genetic variations in DPP1 are associated with susceptibility to asthma (ASTHMA). The most common chronic disease affecting children and young adults. It is a complex genetic disorder with a heterogeneous phenotype, largely attributed to the interactions among many genes and between these genes and the environment. It is characterized by recurrent attacks of paroxysmal dyspnea, with weezing due to spasmodic contraction of the bronchi.
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TMPH-01035 | CNR1 Protein-VLP, Human, Recombinant (His) | Human | HEK293 | ||
G-protein coupled receptor for endogenous cannabinoids (eCBs), including N-arachidonoylethanolamide (also called anandamide or AEA) and 2-arachidonoylglycerol (2-AG), as well as phytocannabinoids, such as delta(9)-tetrahydrocannabinol (THC). Mediates many cannabinoid-induced effects, acting, among others, on food intake, memory loss, gastrointestinal motility, catalepsy, ambulatory activity, anxiety, chronic pain. Signaling typically involves reduction in cyclic AMP. In the hypothalamus, may have a dual effect on mitochondrial respiration depending upon the agonist dose and possibly upon the cell type. Increases respiration at low doses, while decreases respiration at high doses. At high doses, CNR1 signal transduction involves G-protein alpha-i protein activation and subsequent inhibition of mitochondrial soluble adenylate cyclase, decrease in cyclic AMP concentration, inhibition of protein kinase A (PKA)-dependent phosphorylation of specific subunits of the mitochondrial electron transport system, including NDUFS2. In the hypothalamus, inhibits leptin-induced reactive oxygen species (ROS) formation and mediates cannabinoid-induced increase in SREBF1 and FASN gene expression. In response to cannabinoids, drives the release of orexigenic beta-endorphin, but not that of melanocyte-stimulating hormone alpha/alpha-MSH, from hypothalamic POMC neurons, hence promoting food intake. In the hippocampus, regulates cellular respiration and energy production in response to cannabinoids. Involved in cannabinoid-dependent depolarization-induced suppression of inhibition (DSI), a process in which depolarization of CA1 postsynaptic pyramidal neurons mobilizes eCBs, which retrogradely activate presynaptic CB1 receptors, transiently decreasing GABAergic inhibitory neurotransmission. Also reduces excitatory synaptic transmission. In superior cervical ganglions and cerebral vascular smooth muscle cells, inhibits voltage-gated Ca(2+) channels in a constitutive, as well as agonist-dependent manner. In cerebral vascular smooth muscle cells, cannabinoid-induced inhibition of voltage-gated Ca(2+) channels leads to vasodilation and decreased vascular tone. Induces leptin production in adipocytes and reduces LRP2-mediated leptin clearance in the kidney, hence participating in hyperleptinemia. In adipose tissue, CNR1 signaling leads to increased expression of SREBF1, ACACA and FASN genes. In the liver, activation by endocannabinoids leads to increased de novo lipogenesis and reduced fatty acid catabolism, associated with increased expression of SREBF1/SREBP-1, GCK, ACACA, ACACB and FASN genes. May also affect de novo cholesterol synthesis and HDL-cholesteryl ether uptake. Peripherally modulates energy metabolism. In high carbohydrate diet-induced obesity, may decrease the expression of mitochondrial dihydrolipoyl dehydrogenase/DLD in striated muscles, as well as that of selected glucose/ pyruvate metabolic enzymes, hence affecting energy expenditure through mitochondrial metabolism. In response to cannabinoid anandamide, elicits a proinflammatory response in macrophages, which involves NLRP3 inflammasome activation and IL1B and IL18 secretion. In macrophages infiltrating pancreatic islets, this process may participate in the progression of type-2 diabetes and associated loss of pancreatic beta-cells.; Binds both 2-AG and anandamide.; Only binds 2-AG with high affinity. Contrary to its effect on isoform 1, 2-AG behaves as an inverse agonist on isoform 2 in assays measuring GTP binding to membranes.; Only binds 2-AG with high affinity. Contrary to its effect on isoform 1, 2-AG behaves as an inverse agonist on isoform 3 in assays measuring GTP binding to membranes.
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TMPH-01890 | KCNA1 Protein, Human, Recombinant (His) | Human | E. coli | ||
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the kidney. Contributes to the regulation of the membrane potential and nerve signaling, and prevents neuronal hyperexcitability. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel. Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA1 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure. In contrast, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation. Regulates neuronal excitability in hippocampus, especially in mossy fibers and medial perforant path axons, preventing neuronal hyperexcitability. Response to toxins that are selective for KCNA1, respectively for KCNA2, suggests that heteromeric potassium channels composed of both KCNA1 and KCNA2 play a role in pacemaking and regulate the output of deep cerebellar nuclear neurons. May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons. May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) release. Plays a role in regulating the generation of action potentials and preventing hyperexcitability in myelinated axons of the vagus nerve, and thereby contributes to the regulation of heart contraction. Required for normal neuromuscular responses. Regulates the frequency of neuronal action potential firing in response to mechanical stimuli, and plays a role in the perception of pain caused by mechanical stimuli, but does not play a role in the perception of pain due to heat stimuli. Required for normal responses to auditory stimuli and precise location of sound sources, but not for sound perception. The use of toxins that block specific channels suggest that it contributes to the regulation of the axonal release of the neurotransmitter dopamine. Required for normal postnatal brain development and normal proliferation of neuronal precursor cells in the brain. Plays a role in the reabsorption of Mg(2+) in the distal convoluted tubules in the kidney and in magnesium ion homeostasis, probably via its effect on the membrane potential.
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TMPH-03256 | CNR1 Protein, Rat, Recombinant (His) | Rat | in vitro E. coli expression system | ||
G-protein coupled receptor for cannabinoids, including endocannabinoids (eCBs), such as N-arachidonoylethanolamide (also called anandamide or AEA) and 2-arachidonoylglycerol (2-AG). Mediates many cannabinoid-induced effects, acting, among others, on food intake, memory loss, gastrointestinal motility, catalepsy, ambulatory activity, anxiety, chronic pain. Signaling typically involves reduction in cyclic AMP. In the hypothalamus, may have a dual effect on mitochondrial respiration depending upon the agonist dose and possibly upon the cell type. Increases respiration at low doses, while decreases respiration at high doses. At high doses, CNR1 signal transduction involves G-protein alpha-i protein activation and subsequent inhibition of mitochondrial soluble adenylate cyclase, decrease in cyclic AMP concentration, inhibition of protein kinase A (PKA)-dependent phosphorylation of specific subunits of the mitochondrial electron transport system, including NDUFS2. In the hypothalamus, inhibits leptin-induced reactive oxygen species (ROS) formation and mediates cannabinoid-induced increase in SREBF1 and FASN gene expression. In response to cannabinoids, drives the release of orexigenic beta-endorphin, but not that of melanocyte-stimulating hormone alpha/alpha-MSH, from hypothalamic POMC neurons, hence promoting food intake. In the hippocampus, regulates cellular respiration and energy production in response to cannabinoids. Involved in cannabinoid-dependent depolarization-induced suppression of inhibition (DSI), a process in which depolarization of CA1 postsynaptic pyramidal neurons mobilizes eCBs, which retrogradely activate presynaptic CB1 receptors, transiently decreasing GABAergic inhibitory neurotransmission. Also reduces excitatory synaptic transmission. In superior cervical ganglions and cerebral vascular smooth muscle cells, inhibits voltage-gated Ca(2+) channels in a constitutive, as well as agonist-dependent manner. Induces leptin production in adipocytes and reduces LRP2-mediated leptin clearance in the kidney, hence participating in hyperleptinemia. In adipose tissue, CNR1 signaling leads to increased expression of SREBF1, ACACA and FASN genes. In the liver, activation by endocannabinoids leads to increased de novo lipogenesis and reduced fatty acid catabolism, associated with increased expression of SREBF1/SREBP-1, GCK, ACACA, ACACB and FASN genes. May also affect de novo cholesterol synthesis and HDL-cholesteryl ether uptake. Peripherally modulates energy metabolism. In high carbohydrate diet-induced obesity, may decrease the expression of mitochondrial dihydrolipoyl dehydrogenase/DLD in striated muscles, as well as that of selected glucose/ pyruvate metabolic enzymes, hence affecting energy expenditure through mitochondrial metabolism. In response to cannabinoid anandamide, elicits a proinflammatory response in macrophages, which involves NLRP3 inflammasome activation and IL1B and IL18 secretion. In macrophages infiltrating pancreatic islets, this process may participate in the progression of type-2 diabetes and associated loss of pancreatic beta-cells.
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