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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. GC45549 Pitstop2 Pitstop2是一种网格蛋白抑制剂,可抑制网格蛋白末端结构域的两性结合,IC50值为12μM。
  3. GC45545 Phanerosporic Acid

    Phanerosporic Acid

    A fungal metabolite with antibacterial and antifungal activity
  4. GC45539 Pantoprazole-d6

    BY1023-d6; SKF96022-d6

    An internal standard for the quantification of pantoprazole
  5. GC45538 Oxychlororaphine

    吩嗪-1-甲酰胺,phenazine-1-carboxamide

    A microbial metabolite with diverse biological activities
  6. GC45536 Oleic Acid-13C

    油酸-1-13C,9-cis-Octadecenoic acid-13C; 9Z-Octadecenoic acid-13C

    An internal standard for the quantification of oleic acid
  7. GC45531 N-α-Benzoyl-L-Arginine ethyl ester (hydrochloride)

    BAEE, Bz-Arg-OEt, NSC 86159

    A nonpeptide substrate of proteases and deiminases
  8. GC45515 MX1013

    CV1013; Z-VD-FMK

    A dipeptide pan-caspase inhibitor
  9. GC45513 MGR1 A ROS-generating probe
  10. GC45505 Martinomycin

    LL-D 37187α

    A polyether antibiotic
  11. GC45488 Isosorbide Dinitrate

    硝酸异山梨酯; ISDN

    A nitric oxide donor
  12. GC45467 Harzianum A A trichothecene fungal metabolite
  13. GC45461 Gliorosein A fungal metabolite
  14. GC45455 Fluticasone 17β-Carboxylic Acid

    氟米松酸

    An intermediate in the synthesis of fluticasone propionate
  15. GC45453 Florfenicol-d3

    氟苯尼考胺-D3,(-)-Florfenicol-d3; SCH-25298-d3

    An internal standard for the quantification of florfenicol
  16. GC45449 Erythromycylamine

    (9S)-红霉胺

    A macrolide antibiotic
  17. GC45444 Eicosapentaenoic Acid-d5 MaxSpec• Standard

    EPA-d5; Timnodonic acid-d5

    An internal standard for the quantification of EPA
  18. GC45442 DSPE-MPEG(2000) (sodium salt)

    1,2-Distearoyl-rac-glycero-3-PE-N-Polyethyleneglycol-2000, 1,2-Distearoyl-rac-glycerol-3-Phosphatidylethanolamine-N-Polyethyleneglycol-2000, 1,2-Distearoyl-rac-glycerol-3-Phosphoethanolamine-N-Polyethyleneglycol-2000, 1,2-DSPE-MPEG(2000)

    A PEGylated form of DSPE
  19. GC45440 Doxycycline-d3 (hyclate)

    一种用于量化多西环素的内部标准

  20. GC45416 Cyclo(L-Pro-L-Val)

    环(L-脯-L-缬)二肽

    A diketopiperazine
  21. GC45413 Cridanimod (sodium salt)

    吖啶酮乙酸钠

    An inducer of type I interferon production
  22. GC45411 Clofazimine-d7 An internal standard for the quantification of clofazimine
  23. GC45410 cis-6-Hexadecenoic Acid-d19

    C16:1(6Z)-d19, C16:1Δ6-d19, C16:1ω10c-d19, Sapienic Acid-d19

    An internal standard for the quantification of cis-6-hexadecenoic acid
  24. GC45409 Ciclesonide-d7

    环索奈德 d7

    An internal standard for the quantification of ciclesonide
  25. GC45388 Averantin

    1,3,6,8-四羟基-2-(1-羟基己基)-蒽醌

    A fungal metabolite
  26. GC45384 Arachidic Acid-d2

    氘代二十烷酸(2,2-D2),Icosanoic acid-d2

    An internal standard for the quantification of arachidic acid
  27. GC45383 Antibiotic PF 1052 A fungal metabolite
  28. GC45379 Alloxan (hydrate)

    阿脲 一水合物

    A toxin that selectively eliminates pancreatic β-cells
  29. GC45375 ACTH (1-39) (trifluoroacetate salt)

    Adrenocorticotropic Hormone (1-39)

    A MC2R agonist
  30. GC45374 ACTH (1-17) (human, mouse, rat, porcine, bovine, ovine) (trifluoroacetate salt)

    Adrenocorticotropic Hormone (1-17), SYSMEHFRWGKPVGKKR-OH

    A peptide fragment of ACTH
  31. GC45373 ACTH (1-16) (human, mouse, rat, porcine, bovine, ovine) (trifluoroacetate salt)

    Adrenocorticotropic Hormone (1-16), SYSMEHFRWGKPVGKK-OH

    A peptide fragment of ACTH
  32. GC45357 5-Chlorouracil

    5-氯尿嘧啶

    A chlorinated derivative of uracil
  33. GC45355 5-Amino-6-(D-ribitylamino)uracil (hydrochloride)

    5-Amino-6-ribitylamino-2,4(1H,3H)-Pyrimidinedione; 5-Amino-ribityl-Uracil; 5-A-RU

    A derivative of uracil and precursor to riboflavin

  34. GC45354 4β-Hydroxywithanolide E

    4BETA-羟基醉茄内酯E

    A withanolide with anti-inflammatory and anticancer activities
  35. GC45337 3-Hydroxyterphenyllin

    NSC 299113

    A fungal metabolite with diverse biological activities
  36. GC45336 3-hydroxy-DL-Kynurenine

    DL-3-羟基犬尿氨酸,DL-3-Hydroxykynurenine

    An active metabolite of tryptophan
  37. GC45307 17(R)-Resolvin D3

    Aspirin-triggered Resolvin D3, 17-epi-Resolvin D3, AT-RvD3, 17(R)-RvD3

    An aspirin-triggered epimer of resolvin D3
  38. GC45285 1,2,3-Trihexanoyl-rac-glycerol

    三己酸甘油酯

    A triacylglycerol
  39. GC45277 (±)-Camphene

    DL-Camphene, NSC 4165

     
  40. GC45274 (+)-Pinoresinol

    松脂素,(+)-Pinoresinol

    A lignan with diverse biological activities
  41. GC45272 (-)-Rasfonin

    拉斯弗宁

    A fungal metabolite
  42. GC37999 β-Anhydroicaritin

    脱水淫羊藿素(淫羊藿素)

    β-Anhydroicaritin is isolated from Boswellia carterii Birdware, has antiosteoporosis, estrogen regulation and antitumor properties.
  43. GC37951 YKL-06-061 YKL 06-061 is a potent and selective salt-inducible kinase (SIK) inhibitor with IC50 of 6.56 nM, 1.77 nM and 20.5 nM for SIK1, SIK2 and SIK3, respectively.
  44. GC37850 Tyrphostin A1

    (4-甲氧基苄烯)丙二腈,Tyrphostin 1; AG9

    Tyrphostin A1(AG9)能抑制巨噬细胞培养中CD40L刺激的IL-12产生和抗原诱导的Th1细胞生成。
  45. GC37809 Tocilizumab

    托珠单抗; Anti-Human IL6R, Humanized Antibody

    Tocilizumab 作为一种人源化单克隆抗体,可以靶向 IL-6 受体的膜结合和可溶形式。
  46. GC37748 TBK1/IKKε-IN-5 TBK1/IKKε-IN-1 (compound 1) is a dual inhibitor of TANK-binding kinase 1 (TBK1) and IκB kinase-ε (IKKε/IKK-i) with IC50 of 1.0 nM and 5.6 nM for TBK1 and IKKε, respectively. TBK1/IKKε inhibition enhances response to PD-1 blockade, which effectively predicts tumor response in vivo.
  47. GC37747 TBK1/IKKε-IN-1 TBK1/IKKε-IN-1 是一种双重 TBK1 和 IKKε 抑制剂,IC50s 值 <100 nM。详细信息请参考专利文献 US20160376283 A1 中 Example 60 中的化合物 274。
  48. GC37705 Suramin

    苏拉明

    A polysulfonated naphthylurea with antiviral, antiparasitic, and anticancer activities
  49. GC37700 Succinyl phosphonate trisodium salt

    琥珀酰膦酸盐

    Succinyl phosphonate trisodium salt (SP) 琥珀酰膦酸三钠盐是 α-酮戊二酸脱氢酶 (KGDHC ) 抑制剂,可有效抑制肌肉,细菌,脑和人成纤维细胞中的 KGDHC。Succinyl phosphonate trisodium salt (SP) 抑制 2-氧代戊二酸脱氢酶 (OGDH),以细胞特异性代谢依赖性方式损害癌细胞的活力。Succinyl phosphonate trisodium salt (SP) 抑制谷氨酸诱导的谷氨酸刺激的海马神经元中的 ROS 产生。
  50. GC37693 STING agonist-4

    CS-0087594, Diamidobenzimidazole STING Agonist-2, diABZI-4, HY-123943, STING Agonist-4, STING Agonist diABZI Compound 2

    A STING agonist
  51. GC37692 STING agonist-3

    CS-0029879, Diamidobenzimidazole STING Agonist, diABZI-3, EX-A3217, HY-103665, STING Agonist-3

    A STING agonist

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