59671PathwayClemastine H1-Antihistamine Immune Response Action PathwayClemastine is a first-generation ethanolamine H1-antihistamine. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. H1-antihistamines act on H1 receptors in T-cells to inhibit the immune response, in blood vessels to constrict dilated blood vessels, and in smooth muscles of lungs and intestines to relax those muscles. Allergies causes blood vessel dilation which causes swelling (edema) and fluid leakage.
Reducing the activity of the NF-κB immune response transcription factor through the phospholipase C and the phosphatidylinositol (PIP2) signalling pathways also decreases antigen presentation and the expression of pro-inflammatory cytokines, cell adhesion molecules, and chemotactic factors. Furthermore, lowering calcium ion concentration leads to increased mast cell stability which reduces further histamine release. First-generation antihistamines readily cross the blood-brain barrier and cause sedation and other adverse central nervous system (CNS) effects (e.g. nervousness and insomnia). Second-generation antihistamines are more selective for H1-receptors of the peripheral nervous system (PNS) and do not cross the blood-brain barrier. Consequently, these newer drugs elicit fewer adverse drug reactions.Drug ActionPW059823CenterPathwayVisualizationContext6010124503000#000099PathwayVisualization5957159671Clemastine H1-Antihistamine Immune Response PathwayClemastine is a first-generation ethanolamine H1-antihistamine. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. H1-antihistamines act on H1 receptors in T-cells to inhibit the immune response, in blood vessels to constrict dilated blood vessels, and in smooth muscles of lungs and intestines to relax those muscles. Allergies causes blood vessel dilation which causes swelling (edema) and fluid leakage.
Reducing the activity of the NF-κB immune response transcription factor through the phospholipase C and the phosphatidylinositol (PIP2) signalling pathways also decreases antigen presentation and the expression of pro-inflammatory cytokines, cell adhesion molecules, and chemotactic factors. Furthermore, lowering calcium ion concentration leads to increased mast cell stability which reduces further histamine release. First-generation antihistamines readily cross the blood-brain barrier and cause sedation and other adverse central nervous system (CNS) effects (e.g. nervousness and insomnia). Second-generation antihistamines are more selective for H1-receptors of the peripheral nervous system (PNS) and do not cross the blood-brain barrier. Consequently, these newer drugs elicit fewer adverse drug reactions.Drug152439Mast Cells Release HistamineSubPathway50277693Compound12068312203587959671Pathway2068327913608Simons FE: H1-receptor antagonists. Comparative tolerability and safety. Drug Saf. 1994 May;10(5):350-80.59671Pathway2068332174351Mignery GA, Sudhof TC: The ligand binding site and transduction mechanism in the inositol-1,4,5-triphosphate receptor. EMBO J. 1990 Dec;9(12):3893-8.59671Pathway34230926499181Zhao Y, Vanhoutte PM, Leung SW: Vascular nitric oxide: Beyond eNOS. J Pharmacol Sci. 2015 Oct;129(2):83-94. doi: 10.1016/j.jphs.2015.09.002. Epub 2015 Sep 28.59671Pathway34233111752352Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. doi: 10.1093/nar/30.1.412.59671Pathway3423322890562Taniguchi K, Urakami M, Takanaka K: [Effects of antiallergic agents on polymorphonuclear leukocytes. The inhibition of arachidonic acid release and superoxide production]. Nihon Yakurigaku Zasshi. 1987 Aug;90(2):97-103. doi: 10.1254/fpj.90.97.59671Pathway3423336701456Hallberg T, Dohlsten M, Baldetorp B: Demonstration of histamine receptors on human platelets by flow cytometry. Scand J Haematol. 1984 Feb;32(2):113-8. doi: 10.1111/j.1600-0609.1984.tb02165.x.59671Pathway3423346387510Dorsch W, Hintschich C, Neuhauser J, Weber J: Sequential histamine inhalations cause increased bronchial histamine reactivity in guinea pigs: role of platelets, thromboxanes and prostacyclin. Naunyn Schmiedebergs Arch Pharmacol. 1984 Sep;327(2):148-55. doi: 10.1007/BF00500910.59671Pathway3423351678430Taniguchi K, Masuda Y, Takanaka K: Inhibitory effects of histamine H1 receptor blocking drugs on metabolic activations of neutrophils. J Pharmacobiodyn. 1991 Feb;14(2):87-93. doi: 10.1248/bpb1978.14.87.59671Pathway3423364074605Thomas RH, Browne PD, Kirby JD: The influence of ranitidine, alone and in combination with clemastine, on histamine-mediated cutaneous weal and flare reactions in human skin. Br J Clin Pharmacol. 1985 Oct;20(4):377-82. doi: 10.1111/j.1365-2125.1985.tb05080.x.59671Pathway3423376449094Thomson NC, Kerr JW: Effect of inhaled H1 and H2 receptor antagonist in normal and asthmatic subjects. Thorax. 1980 Jun;35(6):428-34. doi: 10.1136/thx.35.6.428.59671Pathway34233829126136Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.59671Pathway1CellCL:00000002Platelet CL:00002334CardiomyocyteCL:00007463NeuronCL:00005408Beta cellCL:00006396MyocyteCL:000018723T CellCL:000008428MacrophageCL:00002355HepatocyteCL:000018232Acinar CellCL:000062226Endothelial cellCL:00001157Epithelial CellCL:00000661Homo sapiens9606EukaryoteHuman18Saccharomyces cerevisiae4932EukaryoteYeast12Mus musculus10090EukaryoteMouse5Bos taurus9913EukaryoteCattle17Rattus norvegicus10116EukaryoteRat3Escherichia coli562Prokaryote6Caenorhabditis elegans6239EukaryoteRoundworm4Arabidopsis thaliana3702EukaryoteThale cress10Drosophila melanogaster7227EukaryoteFruit fly157Acinetobacter baumannii 107673Prokaryote138human0046323Eukaryote2Bacteria2ProkaryoteBacteria62Acinetobacter baylyi (strain ATCC 33305 / BD413 / ADP1)62977Prokaryote230Ambystoma mexicanum8296Eukaryoteaxolotl333Elephantidae9780EukaryoteElephant10Cell MembraneGO:00058865CytoplasmGO:000573711Extracellular SpaceGO:00056151CytosolGO:000582919Sarcoplasmic ReticulumGO:00165292MitochondrionGO:00057397Endoplasmic Reticulum MembraneGO:000578924Mitochondrial Intermembrane SpaceGO:000575825Golgi ApparatusGO:000579414Mitochondrial Outer MembraneGO:000574112Mitochondrial Inner MembraneGO:000574313Endoplasmic ReticulumGO:00057836LysosomeGO:000576416Lysosomal LumenGO:004320236MembraneGO:001602015NucleusGO:000563454Endocytic VesicleGO:003013922post-synaptic membraneGO:004521165Presynaptic membraneGO:004273433Outer MembraneGO:00431652Endothelium BTO:00003935cardiocyteBTO:00015391LiverBTO:000075972918PancreasBTO:00009888Blood VesselBTO:000110274116KidneyBTO:00006717189MuscleBTO:00008871411816SkinBTO:00012531542514EyeBTO:00004391532411HeartBTO:0000562731024BrainBTO:0000142891626LungBTO:000076322BladderBTO:000012348Salivary GlandBTO:000120325IntestineBTO:00006487Nervous SystemBTO:000148428StomachBTO:0001307155263Sympathetic Nervous SystemBTO:000183238Myenteric PlexusBTO:000243647Spinal cordBTO:000127932Adrenal CortexBTO:000004514101PW_BS0000142111018PW_BS0000241151012PW_BS0001158511PW_BS000008405105PW_BS0001153761017PW_BS00005315111PW_BS0000152111PW_BS00000211PW_BS0000013081011PW_BS0000241115121PW_BS000111122551PW_BS0001221355171PW_BS00013516212PW_BS000016215114PW_BS0000213551914PW_BS0000353211PW_BS00000346114PW_BS000046471914PW_BS00004749711PW_BS000049422411PW_BS000042432511PW_BS0000435811411PW_BS000058171211PW_BS000017181311PW_BS0000189611PW_BS000009711113PW_BS00007172513PW_BS00007229111PW_BS0000296618518PW_BS000066101711PW_BS0000102811611PW_BS000028101531PW_BS000101205561PW_BS0000241601181PW_BS0001601901118PW_BS0000242137181PW_BS0000241985181PW_BS00002421013181PW_BS0000241644PW_BS0001642851041PW_BS000024151141PW_BS0001513317121PW_BS0000281321121PW_BS00013235625121PW_BS00002834524121PW_BS00002813013121PW_BS0001301141112PW_BS0001147413PW_BS000074228361PW_BS0000245181PW_BS000051124151PW_BS0001244182451PW_BS0001154192551PW_BS000115383751PW_BS0001001251351PW_BS000125409115PW_BS0001151181171PW_BS00011845424171PW_BS00011545525171PW_BS0001153987171PW_BS00011313613171PW_BS0001361371117PW_BS0001372975101PW_BS0000244781010PW_BS00011548924101PW_BS0001152991101PW_BS00002449025101PW_BS0001154957101PW_BS000115209106PW_BS0000245062461PW_BS000115388161PW_BS0001125072561PW_BS000115390761PW_BS0001127906111PW_BS0005248346111PW_BS000549509516PW_BS000050231511PW_BS00002321815181PW_BS00002412815121PW_BS0001284101551PW_BS00011544415171PW_BS00011548515101PW_BS0001155161561PW_BS000115116481123PW_BS00058327151PW_BS000027116985128PW_BS0005831171815128PW_BS0005833211515PW_BS000032810101574PW_BS0005481372161511PW_BS0005921386151381PW_BS0006181390141511PW_BS0006261317815123PW_BS000588892PW_BS0000896531624PW_BS0005086651818PW_BS00050848113PW_BS000048711PW_BS000007101111114PW_BS00057778924113PW_BS00052410569116PW_BS000578105014516PW_BS000577136126116PW_BS00059111398116PW_BS000581136614116PW_BS0005911367221016PW_BS000591136822116PW_BS0005911450481132PW_BS000635113481126PW_BS00058165413621PW_BS0005088705413PW_BS000552926971PW_BS0005589301911PW_BS000559979132301PW_BS000569966241313PW_BS000567105791916PW_BS0005781146141916PW_BS0005831363261916PW_BS000591136481916PW_BS0005911369221916PW_BS0005911417251916PW_BS00063214514819132PW_BS000635145887123PW_BS000635113387126PW_BS000581397113PW_BS0000393872213PW_BS000038451014PW_BS000045778281PW_BS000521787241013PW_BS000524731013PW_BS0000735291016PW_BS00005267181018PW_BS0000671033246513PW_BS0005771055261016PW_BS000578105831013PW_BS0005781144141016PW_BS00058314494836132PW_BS0006351000810123PW_BS0005741453810126PW_BS00063565111PW_BS00006565110624PW_BS00050820473313PW_BS000024828111011PW_BS0005481014111014PW_BS0005771071386513PW_BS000578113881016PW_BS0005811409256513PW_BS0006321414251016PW_BS00063214202465123PW_BS000632142824653333PW_BS000633143624653333PW_BS0006331444476513PW_BS000635111876513PW_BS000579608321PW_BS0005015602410171PW_BS000204965242213PW_BS0005666612617PW_BS00050860251PW_BS0000601867Nitric oxideHMDB0003378The biologically active molecule nitric oxide (NO) is a simple, membrane-permeable gas with unique chemistry. It is formed by the conversion of L-arginine to L-citrulline, with the release of NO. The enzymatic oxidation of L-arginine to L-citrulline takes place in the presence of oxygen and NADPH using flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), heme, thiol, and tetrahydrobiopterin as cofactors. The enzyme responsible for the generation of NO is nitric oxide synthase (E.C. 1.7.99.7; NOS). Three NOS isoforms have been described and shown to be encoded on three distinct genes: neuronal NOS (nNOS, NOS type I), inducible NOS (NOS type II), and endothelial NOS (eNOS, NOS type III). Two of them are constitutively expressed and dependent on the presence of calcium ions and calmodulin to function (nNOS and eNOS), while iNOS is considered non-constitutive and calcium-independent. However, experience has shown that constitutive expression of nNOS and eNOS is not as rigid as previously thought (i.e. either present or absent), but can be dynamically controlled during development and in response to injury. Functionally, NO may act as a hormone, neurotransmitter, paracrine messenger, mediator, cytoprotective molecule, and cytotoxic molecule. NO has multiple cellular molecular targets. It influences the activity of transcription factors, modulates upstream signaling cascades, mRNA stability and translation, and processes the primary gene products. In the brain, many processes are linked to NO. NO activates its receptor, soluble guanylate cyclase by binding to it. The stimulation of this enzyme leads to increased synthesis of the second messenger, cGMP, which in turn activates cGMP-dependent kinases in target cells. NO exerts a strong influence on glutamatergic neurotransmission by directly interacting with the N-methyl-D-aspartate (NMDA) receptor. Neuronal NOS is connected to NMDA receptors (see below) and sharply increases NO production following activation of this receptor. Thus, the level of endogenously produced NO around NMDA synapses reflects the activity of glutamate-mediated neurotransmission. However, there is recent evidence showing that non-NMDA glutamate receptors (i.e. AMPA and type I metabotropic receptors) also contribute to NO generation. Besides its influence on glutamate, NO is known to have effects on the storage, uptake and/or release of most other neurotransmitters in the CNS (acetylcholine, dopamine, noradrenaline, GABA, taurine, and glycine) as well as of certain neuropeptides. Finally, since NO is a highly diffusible molecule, it may reach extrasynaptic receptors at target cell membranes that are some distance away from the place of NO synthesis. NO is thus capable of mediating both synaptic and nonsynaptic communication processes. NO is a potent vasodilator (a major endogenous regulator of vascular tone), and an important endothelium-dependent relaxing factor. NO is synthesized by NO synthases (NOS) and NOS are inhibited by asymmetrical dimethylarginine (ADMA). ADMA is metabolized by dimethylarginine dimethylaminohydrolase (DDAH) and excreted in the kidneys. Lower ADMA levels in pregnant women compared to non-pregnant controls suggest that ADMA has a role in vascular dilatation and blood pressure changes. Several studies show an increase in ADMA levels in pregnancies complicated with preeclampsia. Elevated ADMA levels in preeclampsia are seen before clinical symptoms have developed; these findings suggest that ADMA has a role in the pathogenesis of preeclampsia. In some pulmonary hypertensive states such as ARDS, the production of endogenous NO may be impaired. Nitric oxide inhalation selectively dilates the pulmonary circulation. Significant systemic vasodilation does not occur because NO is inactivated by rapidly binding to hemoglobin. In an injured lung with pulmonary hypertension, inhaled NO produces local vasodilation of well-ventilated lung units and may "steal" blood flow away from unventilated regions. This reduces intrapulmonary shunting and may improve systemic arterial oxygenation. Nitric oxide is a chemical mediator fundamental in the maintenance of adequate tissue perfusion and effective cardiovascular function. The use of nitrates is well established as pharmacological agents but it is only recently that it has been recognized that they act as a source of nitric oxide (PMID: 16966108, 8752507, 17181668, 16005189). Nitric oxide is used as a food additive (EAFUS: Everything Added to Food in the United States).10102-43-9C0053314506816480NITRIC-OXIDE127983DB00435[N]=ONOInChI=1S/NO/c1-2MWUXSHHQAYIFBG-UHFFFAOYSA-Nnitroso30.006129.9979886270nitric oxide00FDB021825Mononitrogen monoxide;Nitric oxide;Nitrogen monoxide;Nitrogen oxide;Nitrogen protoxide;Nitrosyl hydride;Nitrosyl radical;Nitroxide radical;Nitroxyl;(no)(.);[no];Edrf;Endothelium-derived relaxing factor;Monoxido de nitrogeno;Monoxyde d'azote;Nitrogen monooxide;Nitrosyl;No;(.)no;No(.);Oxido de nitrogeno(ii);Oxido nitrico;Oxyde azotique;Oxyde nitrique;Stickstoff(ii)-oxid;StickstoffmonoxidPW_C001867NO4795144799141189621177514115803318120428405123062376693HistamineHMDB0000870Histamine, also known as eramin or ceplene, belongs to the class of organic compounds known as 2-arylethylamines. These are primary amines that have the general formula RCCNH2, where R is an organic group. Histamine exists as a solid, soluble (in water), and a very weakly acidic compound (based on its pKa). Histamine has been found throughout most human tissues, and has also been detected in most biofluids, including feces, saliva, urine, and blood. Within the cell, histamine is primarily located in the myelin sheath. In humans, histamine is involved in the phenbenzamine H1-antihistamine action pathway, the omeprazole action pathway, the levocetirizine H1-antihistamine action pathway, and the propiomazine H1-antihistamine action pathway. Histamine is also involved in several metabolic disorders, some of which include the thiazinamium H1-antihistamine action pathway, the metiamide action pathway, the quetiapine H1-antihistamine action pathway, and the histidinemia pathway. Outside of the human body, histamine can be found in a number of food items such as daikon radish, jicama, caraway, and japanese walnut. This makes histamine a potential biomarker for the consumption of these food products. Histamine is an amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter.51-45-6C0038877418295HISTAMINE753NCCC1=CNC=N1C5H9N3InChI=1S/C5H9N3/c6-2-1-5-3-7-4-8-5/h3-4H,1-2,6H2,(H,7,8)NTYJJOPFIAHURM-UHFFFAOYSA-N2-(1H-imidazol-4-yl)ethan-1-amine111.1451111.0796473030.182histamine01FDB0125961h-imidazole-4-ethanamine;2-(1h-imidazol-4-yl)ethanamine;2-(1h-imidazol-4-yl)ethylamine;2-(1h-imidazol-5-yl)ethanamine;2-(1h-imidazol-5-yl)ethylamine;2-(4-imidazolyl)ethanamine;2-(4-imidazolyl)ethylamine;2-imidazol-4-yl-ethylamine;2-imidazol-4-ylethylamine;4-(2-aminoethyl)-1h-imidazole;4-(2-aminoethyl)imidazole;4-imidazoleethylamine;5-imidazoleethylamine;Eramin;Ergamine;Ergotidine;Free histamine;Hsm;Histamine;L-histamin base;L-histamine;Theramine;B-imidazolyl-4-ethylamine;Beta-aminoethylglyoxaline;Beta-aminoethylimidazole;Beta-aminothethylglyoxaline;Beta-imidazolyl-4-ethylaminePW_C000693Hsm13108315314415115415926731117000830878132111121026122123591135353CalciumHMDB0000464Calcium is essential for the normal growth and maintenance of bones and teeth, and calcium requirements must be met throughout life. Requirements are greatest during periods of growth, such as childhood, during pregnancy and when breast-feeding. Long-term calcium deficiency can lead to osteoporosis, in which the bone deteriorates and there is an increased risk of fractures. Adults need between 1,000 and 1,300 mg of calcium in their daily diet. Calcium is essential for living organisms, particularly in cell physiology, and is the most common metal in many animals. Physiologically, it exists as an ion in the body. Calcium combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Calcium is an important component of a healthy diet. A deficit can affect bone and tooth formation, while overretention can cause kidney stones. Vitamin D is needed to absorb calcium. Dairy products, such as milk and cheese, are a well-known source of calcium. However, some individuals are allergic to dairy products and even more people, particularly those of non-European descent, are lactose-intolerant, leaving them unable to consume dairy products. Fortunately, many other good sources of calcium exist. These include: seaweeds such as kelp, wakame and hijiki; nuts and seeds (like almonds and sesame); beans; amaranth; collard greens; okra; rutabaga; broccoli; kale; and fortified products such as orange juice and soy milk. Calcium has also been found to assist in the production of lymphatic fluids.14127-61-8C0007627129108CA%2b2266DB01373[Ca++]CaInChI=1S/Ca/q+2BHPQYMZQTOCNFJ-UHFFFAOYSA-Ncalcium(2+) ion40.07839.9625911550calcium(2+) ion22FDB003513Ca;Calcium element;Ca(2+);Ca2+;Calcium ion;Calcium, doubly charged positive ionPW_C000353Ca2+2761630385531460129411599321997351046311634611644714784914914215524321165821381727961829379315971316072394229418666478210482228534011157801017179205723221172581607281190117742131183719811842210121981641221528515288151153503086933617738933177600115781541327826635678526345787241307890811480413748058922881826511202201221204654051210491241213004181213774191218503831219231251223704091228951351230993761236131181238704541239364551244033981244761361249241371255712971257114781259814891260092991260504901265334951272032091274345061274603881275025071281053901406767901406778341406955097005Phosphatidylinositol 4,5-bisphosphatePhosphatidylinositol 4,5-bisphosphate is considered to be a practically insoluble (in water) and relatively neutral molecule. Phosphatidylinositol 4,5-bisphosphate has the chemical formula C47H80O19P3, and an average molecular weight of 1042.048. Phosphatidylinositol 4,5-bisphosphate is involved in multiple pathways, some of which are T Cell Receptor Signaling Pathway , BCR Signaling Pathway, T Cell Receptor Signaling Pathway , and BCR Signaling Pathway.24742074CCCCCCCCCCCCCCCCCC(=O)OCC(COP([O-])(=O)O[C@@H]1[C@H](O)[C@H](O)[C@@H](OP([O-])([O-])=O)[C@H](OP([O-])([O-])=O)[C@H]1O)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCCC47H80O19P3InChI=1S/C47H85O19P3/c1-3-5-7-9-11-13-15-17-19-20-22-24-26-28-30-32-34-36-41(49)63-39(37-61-40(48)35-33-31-29-27-25-23-21-18-16-14-12-10-8-6-4-2)38-62-69(59,60)66-45-42(50)43(51)46(64-67(53,54)55)47(44(45)52)65-68(56,57)58/h11,13,17,19,22,24,28,30,39,42-47,50-52H,3-10,12,14-16,18,20-21,23,25-27,29,31-38H2,1-2H3,(H,59,60)(H2,53,54,55)(H2,56,57,58)/p-5/b13-11-,19-17-,24-22-,30-28-/t39?,42-,43+,44+,45-,46-,47-/m1/s1CNWINRVXAYPOMW-WJUYXORRSA-I1042.0481041.450664914-4.593-5-5PW_C097005P45P8056181155Inositol 1,4,5-trisphosphateHMDB0001498Intracellular messenger formed by the action of phospholipase C on phosphatidylinositol 4,5-bisphosphate, which is one of the phospholipids that make up the cell membrane. Inositol 1,4,5-trisphosphate is released into the cytoplasm where it releases calcium ions from internal stores within the cell's endoplasmic reticulum. These calcium ions stimulate the activity of B kinase or calmodulin. (PubChem). Inositol 1,4,5-trisphosphate (InsP3) is traditionally considered to be the messenger that initiates the increase and spreading of the activating Ca2+ wave. In line with this hypothesis, recent evidence suggests that the penetrating sperm delivers into mammalian eggs a novel isoform of phospholipase C (PLC), which promotes the formation of InsP3. The mechanism by which the interacting sperm triggers the production of NAADP and subsequently that of InsP3 remains obscure. (PMID: 15362223).85166-31-0C0124543945616595inositol_1,4,5-trisphosphate388562O[C@@H]1[C@H](O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@@H](O)[C@@H]1OP(O)(O)=OC6H15O15P3InChI=1S/C6H15O15P3/c7-1-2(8)5(20-23(13,14)15)6(21-24(16,17)18)3(9)4(1)19-22(10,11)12/h1-9H,(H2,10,11,12)(H2,13,14,15)(H2,16,17,18)/t1-,2+,3+,4-,5-,6-/m1/s1MMWCIQZXVOZEGG-XJTPDSDZSA-N{[(1R,2S,3R,4R,5S,6R)-2,3,5-trihydroxy-4,6-bis(phosphonooxy)cyclohexyl]oxy}phosphonic acid420.0956419.962379346-1.459InsP30-6FDB0226571d-myo-inositol 1,4,5-trisphosphate;D-myo-inositol 1,4,5-trisphosphate;Inositol 1,4,5-trisphosphate;1,4,5-insp3;D-myo-inositol-1,4,5-triphosphate;Ins(1,4,5)p3;Insp3;Ip3;1d-myo-inositol 1,4,5-trisphosphoric acid;D-myo-inositol 1,4,5-trisphosphoric acid;D-myo-inositol-1,4,5-triphosphoric acid;Inositol 1,4,5-trisphosphoric acidPW_C001155Inotp27416658220372325751427924673871607409218122142856934417816912878211132785161157999918800893088023781219754101224421241225114051245284441250091181250813761261244851265932991266644781277325161281653881282412098819ClemastineHMDB0014428Clemastine is only found in individuals that have used or taken this drug. It is an ethanolamine-derivative, first generation histamine H1 antagonist used in hay fever, rhinitis, allergic skin conditions, and pruritus. It causes drowsiness. [PubChem]Clemastine is a selective histamine H1 antagonist and binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine.15686-51-8C0691326987373825129DB00283CN1CCC[C@@H]1CCO[C@](C)(C1=CC=CC=C1)C1=CC=C(Cl)C=C1C21H26ClNOInChI=1S/C21H26ClNO/c1-21(17-7-4-3-5-8-17,18-10-12-19(22)13-11-18)24-16-14-20-9-6-15-23(20)2/h3-5,7-8,10-13,20H,6,9,14-16H2,1-2H3/t20-,21-/m1/s1YNNUSGIPVFPVBX-NHCUHLMSSA-N(2R)-2-{2-[(1R)-1-(4-chlorophenyl)-1-phenylethoxy]ethyl}-1-methylpyrrolidine343.89343.170292166-5.930clemastine01Clemastina [inn-spanish];Clemastinum [inn-latin];Clemastine fumarate;(+)-(2r)-2-(2-(((r)-p-chloro-alpha-methyl-alpha-phenylbenzyl)oxy)ethyl)-1-methylpyrrolidine;(+)-(2r)-2-[2-[[(r)-p-chloro-alpha-methyl-alpha-phenylbenzyl]oxy]ethyl]-1-methylpyrrolidine;Clemastina;ClemastinumPW_C008819Clemast72290308369DiacylglycerolCompound43357CompoundPW_EC000369Diacylg8023515802362281279Protein kinase C beta typeP05771Calcium-activated and phospholipid-dependent serine/threonine-protein kinase involved in various processes such as regulation of the B-cell receptor (BCR) signalosome, apoptosis and transcription regulation. Plays a key role in B-cell activation and function by regulating BCR-induced NF-kappa-B activation and B-cell suvival. Required for recruitment and activation of the IKK kinase to lipid rafts and mediates phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser-644' and 'Ser- 652', leading to activate the NF-kappa-B signaling. Involved in apoptosis following oxidative damage:in case of oxidative conditions, specifically phosphorylates 'Ser-36' of isoform p66Shc of SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc acts as a reactive oxygen species producer. Acts as a coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and specifically mediating phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag for epigenetic transcriptional activation that prevents demethylation of histone H3 'Lys-4' (H3K4me) by LSD1/KDM1A. Also involved in triglyceride homeostasis. Serves as the receptor for phorbol esters, a class of tumor promotersHMDBP01372PRKCB16p11.2FJ90724612.7.11.13693888800521648041474142773214564511641808Nuclear factor NF-kappa-B p105 subunitP19838NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF- kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF- kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric p65-p50 and RelB-p50 complexes are transcriptional activators. The NF-kappa-B p50-p50 homodimer is a transcriptional repressor, but can act as a transcriptional activator when associated with BCL3. NFKB1 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p105 and generation of p50 by a cotranslational processing. The proteasome-mediated process ensures the production of both p50 and p105 and preserves their independent function, although processing of NFKB1/p105 also appears to occur post- translationally. p50 binds to the kappa-B consensus sequence 5'- GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105HMDBP02145NFKB14q24BC05176514145241472380356811593927143737116914374511711440013214522281014522313721453551386145373139014564713172161-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1Q9NQ66The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes.
HMDBP00222PLCB120p12AL05031513.1.4.1125761427904611646896933718009030880230813612465313619166513619966140927481410437141146214128250142375101114258578914287310561434321050145110136114514011391451631366145187136714558613681455921450145632116414565211342126Inositol 1,4,5-trisphosphate receptor type 1Q14643Intracellular channel that mediates calcium release from the endoplasmic reticulum following stimulation by inositol 1,4,5- trisphosphateHMDBP02849ITPR13p26.1D260701967162794188502108009181361386541409284814103887014104149141284926141317930142028979142586789142587966142721141428931057143435114614510913631451381364145186136914551714171455941451145646145814565311332712Voltage-dependent P/Q-type calcium channel subunit alpha-1AO00555Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1A gives rise to P and/or Q-type calcium currents. P/Q-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by the funnel toxin (Ftx) and by the omega-agatoxin- IVA (omega-Aga-IVA). They are however insensitive to dihydropyridines (DHP), and omega-conotoxin-GVIA (omega-CTx-GVIA)HMDBP07491CACNA1A19p13AC09878119393994238850322813637274139529451395305113970577813990548140632714064478714099730814100073141348521419326714196921428661033142870105514289810581434281144145588136714559614491456021361145643100014564914532720Voltage-dependent L-type calcium channel subunit beta-1Q02641The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targetingHMDBP07499CACNB117q21-q22CH471152193839276945351514354052509665807532281361336511395315113970677813981020413990648140154308140556787140585741406337140638828141001731419336714197021423971014142872105514291010581429571033142982107114342911441451441138145194136714547914091455201414145526142014554614281455651436145597144914560313611456141444145644100014565014532706Voltage-dependent calcium channel subunit alpha-2/delta-2Q9NY47The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR CACNA1D) and possibly T-type (CACNA1G). Overexpression induces apoptosisHMDBP07485CACNA2D23p21.3AJ2513681940392768453514143539525095658499228136132651139532511397077781398092041399074814058674140624308140634714063782814064378714099973141687671419712142395101414287110551429111058142955103314298010711431891118143430114414548714091455241420145544142814556314361455891367145598144914560413611456121444145642100014565114531740Guanine nucleotide-binding protein G(q) subunit alphaP50148Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systemsHMDBP02022GNAQ9q21U430831516314693231827158828363081360056081361856651362016613850556014088648141042714114521411757314258478914287810561434311050145587136814559314501456011361145640100014564814531108Protein kinase C alpha typeP17252PKC is activated by diacylglycerol which in turn phosphorylates a range of cellular proteins. PKC also serves as the receptor for phorbol esters, a class of tumor promotersHMDBP01180PRKCA17q22-q23.2X5247912.7.11.1342242802818136200661398591414093748142892105614511313611451421139145164136614519213681455951450145641100014565810552116Histamine H1 receptorP35367In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous systemHMDBP02823HRH13p25X7678616731217000930814119078714332396514361366114562152145625145314563010006638protein kinase C beta1PW_P0066381438012797443533693878988Nuclear factor NF-kappa-B p105 subunit1PW_P00098811171808115088Phospholipase C1PW_P0150882513121615363531411522270Inositol 1,4,5-trisphosphate receptor type 11PW_P00027028921264777L type Calcium channel1PW_P00077787627121877272018782706215087Gq protein signaling cascade1PW_P01508725130174014114421142Protein kinase C1PW_P0011421304110816635Histamine H1 receptor1PW_P006635143762116217623PW_R217623Right839176970051Compoundfalse8391773691ElementCollectionfalse83917811551Compoundfalse207193150883.1.4.1114002PW_T014002144243531Compound9302Right49842702022-01-31T01:00:30-07:002022-01-31T01:00:30-07:0093011095PW_T011095114983531Compound152Right22347772020-12-07T03:17:29-07:002020-12-07T03:17:29-07:00215240PW_T015240Diffusion1568988191Compound601000Right245ActivationPW_I0002454896638ProteinComplex1490988ProteinComplex13528ActivationPW_I003528705515087ProteinComplex1705615088ProteinComplex1242ActivationPW_I0002424831155Compound1484270ProteinComplex13990ActivationPW_I00399079791142ProteinComplex17980777ProteinComplex1509ActivationPW_I0005091017369ElementCollection110181142ProteinComplex14132ActivationPW_I0041328263693Compound182646635ProteinComplex14728ActivationPW_I00472894556635ProteinComplex1945615087ProteinComplex1244ActivationPW_I000244487353Compound14886638ProteinComplex14744ActivationPW_I0047449487369ElementCollection194886638ProteinComplex14729InhibitionPW_I00472994578819Compound194586635ProteinComplex132037181867113464false2937375910regular78783203924693100081false118050510regular200190320392535311649false2357162420regular100253203927353116451false1910156720regular7878320393097005116481false947119110regular20020032039311155116481false1562119410regular200190320393235311649false1247124910regular100253203935353145751false1382156710regular787832039363535151false191256710regular7878320399788191000157false93050510regular2001903204807881960157false93010510regular20019026669369371164false1442104912regular100901248200127911642false233215748proteinregular1507012482011808131799false233219968subunitregular15070124820721611642false122212548proteinregular1507012482092126145878false160015468subunitregular13512012482102712100076false17468158subunitregular1507012482112720100076false20118158subunitregular1507012482122706100077false18718008subunitregular160801248213174010002false122210198proteinregular150701248214110810002false14179098subunitregular1507012482162116100080false11757558subunitregular2001309806376638595711164124141512482005453832039254399528Cofactor9806389885957113171241416124820198064415088595711164124142212482075454032039324399549Cofactor9806462705957114581241424124820998064777759571100012414251248210124142612482111241427124821298064815087595711000124142812482139806491142595711000124142912482149806516635595711000124143112482164399528M2192 1554 L2192 1604 L2242 1554 z10true184399532M2407 1644 C2406 1689 2407 1950 2407 1996 149false18trueM 1809.0096189432334 825 L 1822 817.5 L 1809.0096189432334 810false4399533M407 1266.5 C377 1266.5 1952 1132 1922 1132 149true18trueM 1044.9468550441647 614.261556296296 L 1030 613 L 1036.380887721186 626.5751343230784false4399536M1280 505 C1281 473 1282 441 1282 425 5false18trueM 397.79386831313315 293.1694870164077 L 385 301 L 398.1783573250214 308.1645584800499false4399546M1147 1291 C1177 1291 1192 1289 1222 1289 5false184399547M1562 1289 C1532 1289 1402 1289 1372 1289 5false18trueM 25.946855044164835 1416.261556296296 L 11 1415 L 17.380887721185843 1428.5751343230784false4399548M1492 1149 C1490 1246 1442 1288 1372 1289 5false18trueM 25.946855044164835 1416.261556296296 L 11 1415 L 17.380887721185843 1428.5751343230784false4399549M1412 1229 L1412 1279 L1462 1229 z10true184399554M1460 1606 C1490 1606 1570 1606 1600 1606 83false184399555M1910 1606 C1880 1606 1765 1606 1735 1606 83false18trueM 25.946855044164835 1362.261556296296 L 11 1361 L 17.380887721185843 1374.5751343230784false4399556M1951 645 C1951 675 1951 770 1951 800 83false184399557M1949 1567 C1949 1537 1951 910 1951 880 83false18trueM 795.9468550441649 106.26155629629604 L 781 105 L 787.3808877211858 118.57513432307834false4399558M1297 1089 C1297 1119 1467 1132.75 1467 1162.75 149true184399559M1297 1254 C1297 1224 1297 1119 1297 1089 149false18trueM 67.94685504416483 632.261556296296 L 53 631 L 59.38088772118584 644.5751343230784false4399560M1662 1384 C1662 1414 1652 1417.5 1652 1447.5 149true184399561M1665 1546 C1665 1516 1662 1414 1662 1384 149false18trueM 25.946855044164835 1182.261556296296 L 11 1181 L 17.380887721185843 1194.5751343230784false4399562M1492 909 C1492 879 1493 881 1493 851 C1557 849 1693 850 1746 850 149false18trueM 1288.0096189432334 1148.5 L 1301 1141 L 1288.0096189432334 1133.5false4399563M1951 880 C1951 910 2191 947 2191 977 149true18trueM 315.94685504416486 801.261556296296 L 301 800 L 307.38088772118584 813.5751343230784false4399564M1492 1049 C1492 1019 1552 1094 1552 1064 149true184399565M1492 979 C1492 1009 1492 1019 1492 1049 149false18trueM 174.94685504416483 507.261556296296 L 160 506 L 166.38088772118584 519.5751343230784false4399578M1280 695 C1280 725 1280 750 1280 780 149true184399579M1280 780 C1280 750 1280 725 1280 695 149false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false4399580M1300 870 C1300 900 1297 989 1297 1019 149true184399581M1297 1019 C1297 989 1300 900 1300 870 149false18trueM 430.94685504416486 190.26155629629605 L 416 189 L 422.38088772118584 202.57513432307834false4399625M1988 1606 C2018 1606 2302 1609 2332 1609 149true184399626M2332 1609 C2302 1609 2018 1606 1988 1606 149false18trueM 1717.9468550441647 814.261556296296 L 1703 813 L 1709.380887721186 826.5751343230784false4399639M2407 1574 C2407 1513 2406.5 1142 2406.5 1102 C2310.5 1104 1626 1097 1542 1099 149false18trueM 1041.9468550441647 637.261556296296 L 1027 636 L 1033.380887721186 649.5751343230784false4399640M1542 1099 C1572 1099 1839.5 1094 1869.5 1094 149true184399726M1030 695 C1060 695 1185 825 1215 825 148true184399727M1215 825 C1068 821 1031 776 1030 695 148false18falsetrueM 19.565967322978995 79.68642197321769 L 11 92 L 2.4340326770210066 104.313578026782314401615M1030 295 C1030 325 1030 475 1030 505 83true184401616M1030 505 C1030 475 1030 325 1030 295 83false18trueM 25.946855044164835 88.26155629629604 L 11 87 L 17.380887721185843 100.57513432307834false938612595712176231164380718332039304399546Left380718432039314399547Right25296266694399548Right890922207193980644108659140025957121796432039354399554Left21796532039274399555Right526859806464984108660110955957121796632039364399556Left21796732039274399557Right526869806472234108881152405957121840432048074401615Left21840532039974401616Right17059245595711317216899806374399532Left216909806384399533Right170613528595712216919806484399558Left216929806444399559Right17062242595711164636832039314399560Left216939806464399561Right170633990595712216949806494399562Left216959806474399563Right170645095957110502947266694399564Left216969806494399565Right170684132595711000637032039244399578Left217019806514399579Right170694728595711000217029806514399580Left217039806484399581Right17079244595711164637532039274399625Left217169806374399626Right1708347445957111642949266694399640Left217219806374399639Right170984729595711000639232039974399726Left217359806514399727Right1208735243959571217false120735516regular11818432039244399536Right491726159018211.61.60314327267491728179314910.80.801252400274491729161515591.01.0017471021014917302259392.62.607169200200491750177021781.31.316023280360492022250514650.80.8-85214902404922816501401.01.005217256109478833M875 912.6666259765625 C875 862.6666259765625 925 812.6666259765625 975 812.6666259765625 C1520 812.6666259765625 2230 812.6666259765625 2775 812.6666259765625 C2825 812.6666259765625 2875 862.6666259765625 2875 912.6666259765625 C2875 1309.6666259765625 2875 1826.6666259765625 2875 2223.6666259765625 C2875 2273.6666259765625 2825 2323.6666259765625 2775 2323.6666259765625 C2230 2323.6666259765625 1520 2323.6666259765625 975 2323.6666259765625 C925 2323.6666259765625 875 2273.6666259765625 875 2223.6666259765625 C875 1826.6666259765625 875 1309.6666259765625 875 912.6666259765625 1true60.00.0478834M1026 1573 C1026 1523 1076 1473 1126 1473 C1258 1473 1430 1473 1562 1473 C1612 1473 1662 1523 1662 1573 C1662 1605 1662 1647 1662 1679 C1662 1729 1612 1779 1562 1779 C1430 1779 1258 1779 1126 1779 C1076 1779 1026 1729 1026 1679 C1026 1647 1026 1605 1026 1573 91true6636.0306.0478843M2228 1977 C2228 1927 2278 1877 2328 1877 C2372 1877 2430 1877 2474 1877 C2524 1877 2574 1927 2574 1977 C2574 2009 2574 2049 2574 2081 C2574 2131 2524 2181 2474 2181 C2430 2181 2372 2181 2328 2181 C2278 2181 2228 2131 2228 2081 C2228 2049 2228 2009 2228 1977 93true6346.0304.0478844M123 347 C124 471 128 2207 128 2354 84false65.02007.0900924235Nucleus22002097201.91.920015900928235↑ Antigen Presentation24901589201.61.620015900929235↑ Pro-inflammatory Cytokines, Cell Adhesion Molecules, Chemotactic Factors24911666141.61.620015900930235↑ Mediator Release17781636101.91.920015900931235↓ Mast Cell Stabilization17761716201.91.920015900933235Endoplamic Reticulum10901405201.61.62001590093615There is an overall decrease in calcium levels in the cytosol caused by the inhibition of the Gq signaling cascade19551251202.62.616015900937235Cytosol2215874201.91.920015900938235T Cell2278729202.02.02001590093915Clemastine antagonizes Histamine H1 receptors in endothelial cells, preventing histamine from activating the receptor1398434202.82.816015900984235T Cell260904202.22.22001528437650611678503502899235139202049200128438514962037104714871640176441#FFEEDE459327728438619652001225018962559216939#FFF9C9430927328438812647012635284723514#F8B0B037211999