Immunology/Inflammation
The immune and inflammation-related pathway including the Toll-like receptors pathway, the B cell receptor signaling pathway, the T cell receptor signaling pathway, etc.
Toll-like receptors (TLRs) play a central role in host cell recognition and responses to microbial pathogens. TLR4 initially recruits TIRAP and MyD88. MyD88 then recruits IRAKs, TRAF6, and the TAK1 complex, leading to early-stage activation of NF-κB and MAP kinases [1]. TLR4 is endocytosed and delivered to intracellular vesicles and forms a complex with TRAM and TRIF, which then recruits TRAF3 and the protein kinases TBK1 and IKKi. TBK1 and IKKi catalyze the phosphorylation of IRF3, leading to the expression of type I IFN [2].
BCR signaling is initiated through ligation of mIg under conditions that induce phosphorylation of the ITAMs in CD79, leading to the activation of Syk. Once Syk is activated, the BCR signal is transmitted via a series of proteins associated with the adaptor protein B-cell linker (Blnk, SLP-65). Blnk binds CD79a via non-ITAM tyrosines and is phosphorylated by Syk. Phospho-Blnk acts as a scaffold for the assembly of the other components, including Bruton’s tyrosine kinase (Btk), Vav 1, and phospholipase C-gamma 2 (PLCγ2) [3]. Following the assembly of the BCR-signalosome, GRB2 binds and activates the Ras-guanine exchange factor SOS, which in turn activates the small GTPase RAS. The original RAS signal is transmitted and amplified through the mitogen-activated protein kinase (MAPK) pathway, which including the serine/threonine-specific protein kinase RAF followed by MEK and extracellular signal related kinases ERK 1 and 2 [4]. After stimulation of BCR, CD19 is phosphorylated by Lyn. Phosphorylated CD19 activates PI3K by binding to the p85 subunit of PI3K and produce phosphatidylinositol-3,4,5-trisphosphate (PIP3) from PIP2, and PIP3 transmits signals downstream [5].
Central process of T cells responding to specific antigens is the binding of the T-cell receptor (TCR) to specific peptides bound to the major histocompatibility complex which expressed on antigen-presenting cells (APCs). Once TCR connected with its ligand, the ζ-chain–associated protein kinase 70 molecules (Zap-70) are recruited to the TCR-CD3 site and activated, resulting in an initiation of several signaling cascades. Once stimulation, Zap-70 forms complexes with several molecules including SLP-76; and a sequential protein kinase cascade is initiated, consisting of MAP kinase kinase kinase (MAP3K), MAP kinase kinase (MAPKK), and MAP kinase (MAPK) [6]. Two MAPK kinases, MKK4 and MKK7, have been reported to be the primary activators of JNK. MKK3, MKK4, and MKK6 are activators of P38 MAP kinase [7]. MAP kinase pathways are major pathways induced by TCR stimulation, and they play a key role in T-cell responses.
Phosphoinositide 3-kinase (PI3K) binds to the cytosolic domain of CD28, leading to conversion of PIP2 to PIP3, activation of PKB (Akt) and phosphoinositide-dependent kinase 1 (PDK1), and subsequent signaling transduction [8].
References
[1] Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors[J]. Nature immunology, 2010, 11(5): 373-384.
[2] Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity[J]. Immunity, 2011, 34(5): 637-650.
[3] Packard T A, Cambier J C. B lymphocyte antigen receptor signaling: initiation, amplification, and regulation[J]. F1000Prime Rep, 2013, 5(40.10): 12703.
[4] Zhong Y, Byrd J C, Dubovsky J A. The B-cell receptor pathway: a critical component of healthy and malignant immune biology[C]//Seminars in hematology. WB Saunders, 2014, 51(3): 206-218.
[5] Baba Y, Matsumoto M, Kurosaki T. Calcium signaling in B cells: regulation of cytosolic Ca 2+ increase and its sensor molecules, STIM1 and STIM2[J]. Molecular immunology, 2014, 62(2): 339-343.
[6] Adachi K, Davis M M. T-cell receptor ligation induces distinct signaling pathways in naive vs. antigen-experienced T cells[J]. Proceedings of the National Academy of Sciences, 2011, 108(4): 1549-1554.
[7] Rincón M, Flavell R A, Davis R A. The Jnk and P38 MAP kinase signaling pathways in T cell–mediated immune responses[J]. Free Radical Biology and Medicine, 2000, 28(9): 1328-1337.
[8] Bashour K T, Gondarenko A, Chen H, et al. CD28 and CD3 have complementary roles in T-cell traction forces[J]. Proceedings of the National Academy of Sciences, 2014, 111(6): 2241-2246.
Targets for Immunology/Inflammation
- Cyclic GMP-AMP Synthase(1)
- Apoptosis(137)
- 5-Lipoxygenase(18)
- TLR(106)
- Papain(2)
- PGDS(1)
- PGE synthase(26)
- SIKs(10)
- IκB/IKK(83)
- AP-1(2)
- KEAP1-Nrf2(47)
- NOD1(1)
- NF-κB(265)
- Interleukin Related(129)
- 15-lipoxygenase(2)
- Others(10)
- Aryl Hydrocarbon Receptor(35)
- CD73(16)
- Complement System(46)
- Galectin(30)
- IFNAR(19)
- NO Synthase(78)
- NOD-like Receptor (NLR)(37)
- STING(84)
- Reactive Oxygen Species(434)
- FKBP(14)
- eNOS(4)
- iNOS(24)
- nNOS(21)
- Glutathione(37)
- Adaptive Immunity(144)
- Allergy(129)
- Arthritis(25)
- Autoimmunity(134)
- Gastric Disease(64)
- Immunosuppressants(27)
- Immunotherapeutics(3)
- Innate Immunity(411)
- Pulmonary Diseases(76)
- Reactive Nitrogen Species(43)
- Specialized Pro-Resolving Mediators(42)
- Reactive Sulfur Species(24)
Products for Immunology/Inflammation
- Cat.No. Product Name Information
- GC41740 (S)-p38 MAPK Inhibitor III (S)-p38 MAPK inhibitor III is a methylsulfanylimidazole that inhibits p38 MAP kinase (IC50 = 0.90 μM in vitro).
- GC46356 (Z)-9-Hexadecenol An unsaturated long-chain fatty alcohol with diverse biological activities
- GC38880 (Z)-Leukadherin-1 (Z)-Leukadherin-1 (ADH-503 free base) is an orally active and allosteric CD11b agonist. (Z)-Leukadherin-1 leads to the repolarization of tumor-associated macrophages, reduction in the number of tumor-infiltrating immunosuppressive myeloid cells, and enhances dendritic cell responses.
- GC18787 (±)-Dunnione (±)-Dunnione is a naturally occurring naphthoquinone with diverse biological activities.
- GC13662 (±)-Lisofylline anti-inflammatory agent
- GC46054 1β-Acetoxypolygodial A sesquiterpenoid
- GC49768 1,1’-Ethylidene-bis-(L-tryptophan) A potential impurity found in commercial preparations of L-tryptophan
- GC45285 1,2,3-Trihexanoyl-rac-glycerol
- GC46042 1,2-Dipalmitoyl-13C-sn-glycero-3-PC An internal standard for the quantification of 1,2-dipalmitoyl-sn-glycero-3-PC
- GC45781 1,2-Dipalmitoyl-d31-sn-glycero-3-PC An internal standard for the quantification of 1,2-dipalmitoyl-sn-glycero-3-PC
- GC46385 1,3,4,6-Tetra-O-acetyl-2-azido-2-deoxy-α-D-Mannopyranose A ManNAc analog and building block
- GC46386 1,3,6,8-Pyrenetetrasulfonic Acid (sodium salt hydrate) A synthetic intermediate
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GC41837
1,3,7-Trimethyluric Acid
1,3,7-Trimethyluric acid is a methyl derivative of uric acid and a product of C-8 oxidation of caffeine by cytochrome P450 enzymes.
- GC46387 1,3,7-Trimethyluric Acid-d9 An internal standard for the quantification of 1,3,7-trimethyluric acid
- GC35037 1,3-Dicaffeoylquinic acid 1,3-Dicaffeoylquinic acid is a caffeoylquinic acid derivative, and activates PI3K/Akt.
- GC41855 1,3-Distearoyl-2-Oleoyl-rac-glycerol 1,3-Distearoyl-2-oleoyl-rac-glycerol is a triacylglycerol that contains stearic acid at the sn-1 and sn-3 positions and oleic acid at the sn-2 position.
- GC11173 1,3-PBIT (dihydrobromide) potent inhibitor of iNOS
- GC33314 1,4-Chrysenequinone (Chrysene-1,4-dione) 1,4-Chrysenequinone (Chrysene-1,4-dione), a polycyclic aromatic quinone, acts as an activator of aryl hydrocarbon receptor (AhR).
- GC14627 1,4-PBIT (dihydrobromide) potent inhibitor of purified human iNOS and nNOS
- GC40706 1,6-Dimethoxyphenazine 1,6-Dimethoxyphenazine is a bacterial metabolite that has been found in S.
- GC49294 1-(4-Chlorobenzhydryl)piperazine An inactive metabolite of meclizine and chlorcyclizine
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GC41986
1-Arachidonoyl Lysophosphatidic Acid (ammonium salt)
1-Arachidonoyl lysophosphatidic acid is a phospholipid containing arachidonic acid at the sn-1 position.
- GC41990 1-Decanoyl-rac-glycerol 1-Decanoyl-rac-glycerol is a monoacylglycerol that contains decanoic acid at the sn-1 position.
- GC52186 1-Docosahexaenoyl-2-hydroxy-sn-glycero-3-PC
- GC45957 1-Heptadecanoyl-rac-glycerol A monoacylglycerol
- GC46481 1-Hydroxyphenazine A P. aeruginosa virulence factor
- GC49495 1-Isothiocyanato-6-(methylsulfenyl)-hexane An isothiocyanate with diverse biological activities
- GC45696 1-Lauroyl-rac-glycerol 1-Lauroyl-rac-glycerol (1-1-Lauroyl-rac-glycerol) possesses anti-viral and anti-bacterial activity.
- GC41998 1-Methyl-4-imidazoleacetic Acid (hydrochloride) 1-Methyl-4-imidazoleacetic acid (MIMA) is a stable metabolite of histamine that is produced by the oxidation of the primary metabolite, N-methylhistamine.
- GC13379 1-Naphthyl 3,5-dinitrobenzoate dual 5-lipoxygenase and microsomal prostaglandin E synthase-1 inhibitor
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GC18235
1-O-Hexadecyl-sn-glycerol
1-O-Hexadecyl-sn-glycerol is a bioactive alkyl glyceryl ether.
- GC42010 1-Octanoyl-rac-glycerol 1-Octanoyl-rac-glycerol is a monoacylglycerol that contains octanoic acid at the sn-1 position.
- GC40910 1-Oleoyl-2-hydroxy-sn-glycero-3-PE 1-Oleoyl-2-hydroxy-sn-glycero-3-PE is a naturally-occurring lysophospholipid and an analog of plasmalogen lysophosphatidylethanolamine.
- GC40146 1-Oleoyl-2-Palmitoyl-rac-glycerol 1-Oleoyl-2-palmitoyl-rac-glycerol (1,2-OP) is a diacylglycerol containing oleic acid at the sn-1 position and palmitic acid at the sn-2 position.
- GC18376 1-Palmitoleoyl glycerol 1-Palmitoleoyl glycerol is a bioactive monoacylglycerol.
- GC42020 1-Palmitoyl Lysophosphatidic Acid 1-Palmitoyl lysophosphatidic acid (1-Palmitoyl LPA) is a LPA analog containing palmitic acid at the sn-1 position.
- GC42021 1-Palmitoyl Lysophosphatidic Acid (sodium salt) 1-Palmitoyl lysophosphatidic acid (1-Palmitoyl LPA) is a LPA analog containing palmitic acid at the sn-1 position.
- GC42023 1-Palmitoyl-2-Arachidonoyl-sn-glycero-3-PC 1-Palmitoyl-2-arachidonoyl-sn-glycero-3-PC (PAPC) is a phospholipid containing palmitic acid (16:0) and arachidonic acid (20:4) at the sn-1 and sn-2 positions, respectively, that is found in biological membranes.
- GC42026 1-Palmitoyl-2-hydroxy-sn-glycero-3-PC 1-Palmitoyl-2-hydroxy-sn-glycero-3-PC is an abundant gonadal LPC (lysophosphatidylcholine).
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GC18651
1-Palmitoyl-2-hydroxy-sn-glycero-3-PE
1-Palmitoyl-2-hydroxy-sn-glycero-3-PE is a naturally-occurring lysophospholipid.
- GC42035 1-Palmitoyl-2-Stearoyl-3-Oleoyl-rac-glycerol 1-Palmitoyl-2-stearoyl-3-oleoyl-rac-glycerol is a triacylglycerol that contains palmitic, stearic, and oleic acid at the sn-1, sn-2, and sn-3 positions, respectively.
- GC49071 1-Palmitoyl-d9 Lysophosphatidic Acid An internal standard for the quantification of 1-palmitoyl lysophosphatidic acid
- GC45693 1-Palmitoyl-d9-2-hydroxy-sn-glycero-3-PC A quantitative analytical standard guaranteed to meet MaxSpec® identity, purity, stability, and concentration specifications
- GC42040 1-Stearoyl-2-15(S)-HETE-sn-glycero-3-PE 1-Stearoyl-2-15(S)-HETE-sn-glycero-3-PE is a phospholipid that contains stearic acid at the sn-1 position and 15(S)-HETE at the sn-2 position.
- GC49730 1-Stearoyl-2-15(S)-HETE-sn-glycero-3-PE-d11 An internal standard for the quantification of 1-stearoyl-2-15(S)-HETE-sn-glycero-3-PE
- GC41331 1-Stearoyl-2-hydroxy-sn-glycero-3-PC 1-Stearoyl-2-hydroxy-sn-glycero-3-PC is a saturated 18:0 lysophosphatidylcholine found in plasma and oxidized LDL that is thought to play a role in inflammatory diseases and atherosclerosis.
- GC46498 1-Stearoyl-d35-2-hydroxy-sn-glycero-3-PC An internal standard for the quantification of 1-stearoyl-2-hydroxy-sn-glycero-3-PC
- GC40176 1-Stearoyl-rac-glycerol 1-Stearoyl-rac-glycerol is a monoacylglycerol that contains stearic acid at the sn-1 position.
- GC46501 1-thio-β-D-Glucose Tetraacetate A building block
- GC45785 1-Undecanoyl-rac-glycerol A monoacylglycerol
- GC41865 10'-Desmethoxystreptonigrin 10'-Desmethoxystreptonigrin is an antibiotic originally isolated from Streptomyces and a derivative of the antibiotic streptonigrin.
- GC46400 10(11)-Cl-BBQ Mixture A mixture that acts as an AhR agonist
- GC40971 10(S),17(S)-DiHDHA Protectin D1 (also known as neuroprotectin D1 when produced in neuronal tissues) is a DHA-derived dihydroxy fatty acid that exhibits potent protective and anti-inflammatory activities.
- GC50422 10-Cl-BBQ Potent aryl hydrocarbon receptor (AhR) agonist; orally bioavailable
- GC41866 10-methyl-9-(phenoxycarbonyl) Acridinium (trifluoromethylsulfonate) 10-methyl-9-(phenoxycarbonyl) Acridinium is an acridinium ester that produces fluorescent 10-methyl-9-acridone upon oxidation with hydrogen peroxide, persulfates, and other oxidants in alkaline conditions.
-
GC46402
10-Methyldodec-2-en-4-olide
A bacterial volatile lactone
- GC41868 10-Nitrooleate 10-Nitrooleate (CXA-10), a nitro fatty acid, has potential effects in disease states in which oxidative stress, inflammation, fibrosis, and/or direct tissue toxicity play significant roles.
- GC46404 10-Norparvulenone A fungal metabolite
- GC52423 10Panx (trifluoroacetate salt) A peptide inhibitor of PANX1
- GC41875 11(Z),14(Z)-Eicosadienoic Acid methyl ester 11(Z),14(Z)-Eicosadienoic acid methyl ester is a more lipid soluble form of the ω-6 C20-2 fatty acid 11(Z),14(Z)-eicosadienoic acid, a naturally occurring PUFA.
- GC18634 11-deoxy Prostaglandin E1 11-deoxy Prostaglandin E1 (11-deoxy PGE1) is a synthetic analog of PGE1.
- GC41121 11-deoxy Prostaglandin E2 11-deoxy Prostaglandin E2 (11-deoxy PGE2) is a stable, synthetic analog of PGE2.
- GC40274 11-deoxy Prostaglandin F2α 11-deoxy PGF2α is a synthetic analog of PGF2α.
- GC10821 11-keto-β-Boswellic Acid 11-Keto-beta-boswellic acid (11-Keto-β-boswellic acid) is a pentacyclic triterpenic acid of the oleogum resin from the bark of the Boswellia serrate tree, popularly known as Indian Frankincense. 11-Keto-beta-boswellic acid has the anti-inflammatory activity is primarily due to inhibit 5-lipoxygenase (5-LOX) and subsequent leukotriene and nuclear factor-kappa B (NF-κB) activation and tumor necrosis factor alpha generation production.
- GC41144 11-trans Leukotriene C4 11-trans Leukotriene C4 (11-trans LTC4) is a C-11 double bond isomer of LTC4.
- GC41147 11-trans Leukotriene D4 11-trans Leukotriene D4 (11-trans LTD4) is a C-11 double bond isomer of LTD4.
- GC41149 11-trans Leukotriene E4 Slow isomerization of the C-11 double bond of LTE4 leads to the formation of 11-trans LTE4.
- GC52343 113-O12B An ionizable cationic lipidoid
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GC18637
11β-Prostaglandin F2α
11β-Prostaglandin F2α (11β-PGF2α) is the primary plasma metabolite of PGD2 in vivo.
- GC40447 12(R)-HETE Biosynthesis of 12(R)-HETE in invertebrates is via lipoxygenation of arachidonic acid.
- GC46415 12-Bromododecanoic Acid A halogenated form of lauric acid
- GC41123 12-epi Leukotriene B4 Leukotriene B4 (LTB4) compounds are produced by both enzymatic and non-enzymatic processes.
- GC41332 12-methyl Myristic Acid methyl ester 12-methyl Myristic acid methyl ester is a methylated fatty acid methyl ester that has been found in vermicomposts of cattle manure, carica papaya leaves, and cuticular wax of K.
- GC49808 12-methyl Tridecanoic Acid A methylated fatty acid
- GC41096 12-oxo Leukotriene B4 Leukotriene B4 (LTB4) is a dihydroxy fatty acid derived from arachidonic acid through the 5-LO pathway.
- GC52133 12-Tridecenoic Acid
- GC40578 13,14-dihydro-15-keto Prostaglandin D1 Prostaglandin D1 (PGD1) is the theoretical D-series metabolite of dihomo-γ-linolenic acid (DGLA), but to date it has not been isolated as a natural product.
- GC18783 13,14-dihydro-15-keto Prostaglandin E1 13,14-dihydro-15-keto Prostaglandin E1 (PGE1) is a metabolite of PGE1 with much reduced biological activity.
- GC41333 13-methyl Myristic Acid methyl ester 13-methyl Myristic acid methyl ester is a methylated bacterial fatty acid methyl ester.
- GC49759 13C17-Mycophenolic Acid An internal standard for the quantification of mycophenolic acid
- GC49912 13C20,15N10-Cyclic di-GMP (sodium salt) An internal standard for the quantification of cyclic di-GMP
- GC49390 13C6-4-Nitroaniline An internal standard for the quantification of 4-nitroaniline
- GC41206 14(S)-HDHA Docosahexaenoic acid is a nutritionally-derived ω-3 fatty acid that is abundant in the brain and the retina and is thought to be important in early development and for therapeutic approaches to inflammatory disorders and cancer.
- GC41100 14,15-dehydro Leukotriene B4 Leukotriene B4 (LTB4) is a dihydroxy fatty acid derived from arachidonic acid through the 5-lipoxygenase pathway.
- GC41145 14,15-Leukotriene C4 Leukotrienes (LTs) are a group of acute inflammatory mediators derived from arachidonic acid in leukocytes.
- GC41148 14,15-Leukotriene D4 14,15-Leukotriene D4 (14,15-LTD4) is a member of an alternate class of LTs synthesized by a pathway involving the dual actions of 15- and 12-lipoxygenases (15- and 12-LOs) on arachidonic acid via 15-HpETE and 14,15-LTA4 intermediates.
- GC41150 14,15-Leukotriene E4 Leukotrienes (LTs) are a group of acute inflammatory mediators derived from arachidonic acid in leukocytes.
- GC40763 14-deoxy-11,12-didehydro Andrographolide 14-deoxy-11,12-didehydro Andrographolide is an analog of the natural diterpenoid andrographolide that can be isolated from A.
- GC41918 14-methyl Pentadecanoic Acid methyl ester 14-methyl Pentadecanoic acid methyl ester is a methylated fatty acid methyl ester that has been found in S.
- GC13563 1400W dihydrochloride INOS inhibitor,potent and highly selective
- GC41164 15(R)-15-methyl Prostaglandin D2 15(R)-15-methyl Prostaglandin D2 (15(R)-15-methyl PGD2) is a metabolically stable synthetic analog of PGD2.
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GC41415
15(R)-Lipoxin A4
Lipid-derived lipoxins are produced at the site of vascular and mucosal inflammation where they down-regulate polymorphonuclear leukocyte recruitment and function.
- GC40373 15(S)-HEPE 15(S)-HEPE is a monohydroxy fatty acid synthesized from EPA by the action of 15-LO.
- GC40451 15(S)-HETE 15(S)-HETE is a major arachidonic acid metabolite from the 15-lipoxygenase pathway.
- GC41950 16α-hydroxy Estrone The naturally-occurring estrogens are estrone, estradiol, and estriol.
- GC18778 16,16-dimethyl Prostaglandin A1 16,16-dimethyl PGA1 is a metabolism resistant analog of PGA1.
- GC41942 16,16-dimethyl Prostaglandin A2 16,16-dimethyl PGA2 is a metabolism-resistant analog of PGA2 with a prolonged in vivo half-life.
- GC18803 16,16-dimethyl Prostaglandin F2β 16,16-dimethyl PGF2β is a metabolically stable analog of PGF2β.
- GC41110 16-epi Latrunculin B 16-epi Latrunculin B, first isolated from the Red Sea sponge N.
- GC49068 16-Epiestriol A metabolite of estrone