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Immunology/Inflammation(免疫及炎症)

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.

Products for  Immunology/Inflammation

  1. Cat.No. 产品名称 Information
  2. GC52027 Isolariciresinol

    异落叶松脂素,(+)-Cyclolariciresinol

    A lignan with diverse biological activities
  3. GC52016 Cetirizine N-oxide

    西替利嗪N-氧化物(乙酯)

    An oxidative degradation product of cetirizine
  4. GC52014 Forphenicinol

    Forfenimex

    An immunomodulator and a derivative of forphenicine
  5. GC52013 (±)-10-hydroxy-12(Z)-Octadecenoic Acid

    10-hydroxy-cis-12-Octadecenoic Acid

    An oxylipin and metabolite of linoleic acid
  6. GC52010 (±)-10-hydroxy-12(Z),15(Z)-Octadecadienoic Acid

    αHYA, (±)-10-hydroxy-12(Z),15(Z)-ODE

    An oxylipin gut microbiota metabolite
  7. GC52007 N-hydroxylamine Dapsone

    羟胺氨苯砜

    An active metabolite of dapsone
  8. GC52002 Emavusertib

    CA-4948

    An IRAK4 inhibitor
  9. GC19959 Methylprednisolone acetate

    泼尼松龙EP杂质

    A synthetic glucocorticoid and an ester form of methylprednisolone
  10. GC19941 DL-Leucic Acid
  11. GC19936 Quisinostat dihydrochloride

    QUISINOSTAT二盐酸盐,JNJ-26481585 dihydrochloride

    A pan-HDAC inhibitor
  12. GC49916 Lys-(Des-Arg9, Leu8)-Bradykinin (trifluoroacetate salt)

    Des-Arg10,Leu9-Kallidin, Des-Arg10,Leu9-KD, LysLeu8Des-Arg9-BK, LysLeu8Des-Arg9-Bradykinin

    A bradykinin B1 receptor antagonist
  13. GC49915 Hexa-D-Arginine (trifluoroacetate salt)

    Furin Inhibitor II, Hexa-D-Arg-NH2, Hexa-D-Arginine amide, D6R-NH2, (D)RRRRRR-NH2

    A furin inhibitor
  14. GC49914 Pt(II)-NHC Complex 2C

    Platinum(II)-N-Heterocyclic Carbene Complex 2C

    An inducer of immunogenic cancer cell death
  15. GC49913 Davunetide (acetate)

    AL-108, NAP, NAPVSIPQ

    A neuroprotective ADNP-derived peptide
  16. GC49912 13C20,15N10-Cyclic di-GMP (sodium salt)

    13C20,15N10-c-di-GMP, 13C20,15N10-Cyclic diguanylate, 13C20,15N10-3’,5’-Cyclic diguanylic Acid

    An internal standard for the quantification of cyclic di-GMP
  17. GC49911 Acetyl Hexapeptide-38 (trifluoroacetate salt) A hexapeptide
  18. GC49903 MRT67307 (hydrochloride) A kinase inhibitor
  19. GC49898 Penicillin G-d5 (potassium salt)

    Benzylpenicillin-d5

    An internal standard for the quantification of penicillin G
  20. GC49887 7-(β-Hydroxyethyl)theophylline-d6

    Etophylline-d6, Hydroxyethyltheophylline-d6

    An internal standard for the quantification of 7-(β-hydroxyethyl)theophylline
  21. GC49884 Trigonelline-d3 (chloride)

    Trigonelline-d3 hydrochloride

    An internal standard for the quantification of trigonelline
  22. GC49883 DAPK Substrate Peptide (trifluoroacetate salt)

    Death-associated Protein Kinase Substrate Peptide

    A DAPK1 peptide substrate
  23. GC49876 Pantoprazole N-oxide

    泮托拉唑N-氧化物

    A potential impurity found in bulk preparations of pantoprazole
  24. GC49873 Protectin D1 methyl ester

    Neuroprotectin D1 methyl ester, NPD1 methyl ester, PD1 methyl ester

    An esterified form of protectin D1
  25. GC49871 3’-Azido-2’,3’-dideoxyuridine

    3'-叠氮-2',3'-双脱氧尿苷

    An antiviral nucleoside analog
  26. GC49868 D-α-Tocopheryl Quinone

    α-Tocopherylquinone

    An oxidative metabolite of vitamin E
  27. GC49864 6-Methylpterin

    2-氨基-6-甲基吡嗪并吡啶-4(1H)-酮

    A derivative of folic acid
  28. GC49863 Cytarabine 5′-monophosphate

    ara-CMP, 1-β-D-Arabinofuranosylcytosine 5'-monophosphate, Cytosine Arabinoside monophosphate, NSC 99445

    An active metabolite of cytarabine
  29. GC49860 Pyropheophorbide a methyl ester

    焦脱镁叶绿酸Α甲酯,Pyropheophorbide-a methyl ester

    A photosensitizer
  30. GC49855 Harmalol (hydrochloride hydrate)

    骆驼蓬酚盐酸盐(二水)

    A β-carboline alkaloid and an active metabolite of harmaline
  31. GC49852 Clindamycin (hydrochloride hydrate)

    盐酸克林霉素

    A lincosamide antibiotic
  32. GC49849 3-Aminosalicylic Acid

    3-氨基水杨酸

    A salicylic acid derivative
  33. GC49847 3-hydroxy methyl Cefuroxime

    头孢呋辛钠EP杂质A

    A synthetic intermediate
  34. GC49844 Stercobilin (hydrochloride)

    (-)-Stercobilin, L-Stercobilin

    A fecal pigment and metabolite of bilirubin

  35. GC49838 α-Cortolone

    Β-皮甾酮四醇

    A metabolite of cortisol
  36. GC49837 Gypsogenic Acid

    Astrantiagenin J

    A triterpene acid with antibacterial and trypanocidal activities
  37. GC49836 Benoxaprofen

    氧苯恶唑丙酸,LRCL 3794

    An NSAID
  38. GC49835 Tumulosic Acid

    土莫酸

    A triterpene with diverse biological activities
  39. GC49832 Hydroxymetronidazole

    羟基甲硝唑,Metronidazole-OH

    An active metabolite of metronidazole
  40. GC49827 5-Androstenetriol

    Δ5-AT

    An active metabolite of DHEA
  41. GC49823 2′-C-β-Methylguanosine

    2'-C-甲基鸟苷

    An active nucleoside metabolite of BMS-986094
  42. GC49821 Cyclamidomycin

    赛拉霉素

    A bacterial metabolite with antibiotic activity
  43. GC49819 3-Hydroxy-4-methyl-2(5H)-thiophenone

    头孢氨苄杂质D

    A degradation product of cefaclor
  44. GC49815 Oleuropein aglycone

    3,4-DHPEA-EA

    A polyphenol with diverse biological activities
  45. GC49808 12-methyl Tridecanoic Acid

    12-甲基十三烷酸

    A methylated fatty acid
  46. GC49804 Acridine

    吖啶

    An azaarene
  47. GC49798 Glyphosine

    增甘膦

    A plant growth regulator
  48. GC49793 Bacitracin A (technical grade)

    杆菌肽A

    A polypeptide antibiotic
  49. GC49792 D-(+)-Cellopentaose

    D-(+)-纤维五糖

    An oligosaccharide
  50. GC49790 Reuterin

    罗氏菌素,3-Hydroxypropionaldehyde; 3-Hydroxypropanal

    A bacterial glycerol metabolite with antibacterial activity
  51. GC49786 2-NP-AOZ

    2-NP-呋喃唑酮

    A derivatized metabolite of furazolidone

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