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
- 5-Lipoxygenase(10)
- Papain(1)
- PGDS(1)
- PGE synthase(24)
- SIKs(11)
- IκB/IKK(64)
- AP-1(6)
- KEAP1-Nrf2(65)
- NOD1(1)
- TLR(139)
- NF-κB(235)
- Interleukin Related(167)
- 15-lipoxygenase(2)
- Others(63)
- Aryl Hydrocarbon Receptor(35)
- CD73(14)
- Complement System(57)
- Galectin(12)
- IFNAR(25)
- NO Synthase(74)
- NOD-like Receptor (NLR)(50)
- STING(104)
- Reactive Oxygen Species(454)
- Apoptosis(780)
- FKBP(20)
- eNOS(5)
- iNOS(29)
- nNOS(20)
- Glutathione(55)
- Adaptive Immunity(209)
- Allergy(124)
- Arthritis(34)
- Autoimmunity(179)
- Gastric Disease(95)
- Immunosuppressants(37)
- Immunotherapeutics(4)
- Innate Immunity(560)
- Pulmonary Diseases(108)
- Reactive Nitrogen Species(50)
- Reactive Sulfur Species(28)
- Specialized Pro-Resolving Mediators(50)
- Cyclic GMP-AMP Synthase(2)
- BCL6(3)
- CD20(3)
- CD28(1)
- FAP(7)
- PSMA(7)
- Nuclear Factor of activated T Cells (NFAT)(1)
- Glycoprotein VI(1)
- Tim3(2)
- Hapten(1)
- Nectin-4(2)
- Cat.No. 产品名称 Information
-
GC62453
GZD856 formic
GZD856 formic 是一种有效的和具有口服活性的 PDGFRα/β 抑制剂,IC50 值分别为 68.6 和 136.6 nM。GZD856 formic 也是 Bcr-AblT315I 的抑制剂,对天然 Bcr-Abl 和 T315I 突变型的 IC50 值分别为 19.9 和 15.4 nM。GZD856 formic 具有抗肿瘤活性。
-
GC62452
CD73-IN-4
CD73-IN-4 是一种高效、选择性的亚甲基膦酸 CD73 抑制剂,对人 CD73 作用的 IC50 值为 2.6 nM。CD73-IN-4 在癌症免疫学研究中具有潜在的应用价值。
-
GC62444
SDZ 224-015
SDZ 224-015 是具有口服活性的、IL-1β 转化酶和 caspase-1 的抑制剂。SDZ 224-015 具有抗COVID-19的活性,靶向 Mpro (IC50 of 30 nM)。
-
GC62442
Casein Kinase inhibitor A51
Casein Kinase inhibitor A51 是一种有效且具有口服活性的酪蛋白激酶 1α (CK1α) 抑制剂。Casein Kinase inhibitor A51 可诱导白血病细胞凋亡 (apoptosis),并具有有效的抗白血病活性。
-
GC62426
ASK1-IN-2
ASK1-IN-2 is a potent and orally active inhibitor of apoptosis signal-regulating kinase 1 (ASK1), with an IC50 of 32.8 nM.
-
GC62411
QTX125
QTX125 是一种有效且高度选择性的 HDAC6 抑制剂。与其他 HDAC 相比,QTX125 对 HDAC6 具有出色的选择性。QTX125 具有抗肿瘤作用。
-
GC62406
Moracin O
桑辛素O
Moracin O 是从 Mori Cortex Radicis 中分离出来的 2-芳基苯并呋喃。Moracin O 对缺氧诱导因子 (HIF-1) 表现出强大的体外抑制活性。Moracin O 减少了氧葡萄糖剥夺 (OGD) 诱导的活性氧 (ROS) 的产生。Moracin O 具有神经保护和抗炎作用。 -
GC62399
RA375
RA375 是 RPN13 (26S 蛋白酶体亚基) 抑制剂。RA375 激活 UPR 信号、ROS 产生和凋亡。RA375 的抗肿瘤活性是 RA190的 10 倍。
-
GC62395
TLR7/8 agonist 3
TLR7/8 agonist 3 是一种有效的 TLR7/8 激动剂,源于专利文献 WO2016057618,化合物 II。
-
GC62388
YUM70
YUM70 is a potent inhibitor of glucose-regulated protein 78 (GRP78) inhibitor with an IC50 of 1.5 μM. YUM70 induces endoplasmic reticulum (ER) stress-mediated apoptosis in pancreatic cancer.Although YUM70 inhibits GRP78 enzymatic activity, it increases the expression of GRP78 by increasing the chaperone translation mechanism.
-
GC62372
Cyclic-di-GMP sodium
c-di-GMP sodium; cyclic diguanylate sodium; 5GP-5GP sodium
A bacterial second messenger and cyclic dinucleotide -
GC62370
Sodium thiocyanate
硫氰酸钠; Thiocyanate sodium
Sodium Thiocyanate (NaSCN, Sodium rhodanide, Sodium sulfocyanate, Sodium rhodanate), one of the main sources of the thiocyanate anion, is used as a precursor for the synthesis of pharmaceuticals and other specialty chemicals. Sodium thiocyanate (NaSCN) reduces IL-6, whereas increases IL-10 levels. Sodium thiocyanate also reduces ROS. -
GC62347
CMC2.24
TRB-N0224
CMC2.24 (TRB-N0224) 是一种口服活性三羰基甲烷制剂,通过抑制 Ras 及其下游效应子 ERK1/2 途径对小鼠胰腺肿瘤有效。CMC2.24 也是一种有效的锌依赖性 MMPs 抑制剂,IC50 范围为 2.0-69 μM。CMC2.24 通过恢复软骨内稳态和通过NF-κB/HIF-2α 轴抑制软骨细胞凋亡来减轻骨关节炎的进展。 -
GC62338
GSK-3β inhibitor 3
GSK-3β inhibitor 3 是一种有效,选择性,不可逆和共价的糖原合酶激酶 3β (GSK-3β) 抑制剂,IC50 值为 6.6 μM。GSK-3β inhibitor 3 可用于急性早幼粒细胞白血病的研究。
-
GC62334
AT791
AT791 是一种有效的口服生物利用 TLR7 和 TLR9 抑制剂。AT791 抑制多种人类和小鼠细胞类型的 TLR7 和 TLR9 信号传导,并在体外抑制 DNA-TLR9 相互作用。
-
GC62331
CD73-IN-3
5-[6-甲基-5-[(1S,2R)-2-丙-2-基环丙基]哒嗪-3-基]-1H-嘧啶-2,4-二酮
LY-3475070 is a potent, selective and orally bioavailable inhibitor of the ectoenzyme CD73 (cluster of differentiation 73, 5'-ecto-nucleotidase, 5'-NT, ecto-5'-nucleotidase). -
GC62319
Samuraciclib trihydrochloride
Samuraciclib (CT7001) trihydrochloride 是一种有效的,具有选择性,ATP 竞争性和口服活性的 CDK7 抑制剂,IC50 为 41 nM。Samuraciclib trihydrochloride 对 CDK7 的选择性分别是 CDK1,CDK2 (IC50 为 578 nM),CDK5 和 CDK9 的 45 倍,15 倍,230 倍和 30 倍。Samuraciclib trihydrochloride 以 GI50 值为 0.2-0.3 µM 来抑制乳腺癌细胞系的生长,具有有效的抗肿瘤作用。
-
GC62317
NX-13
NX-13是一种一流的,具有口服活性的肠道限制剂,选择性靶向并激活 NLRX1 通路,诱导免疫代谢改变。NX-13 可降低炎症性肠病的炎症反应。NX-13 可用于克罗恩病和溃疡性结肠炎的研究。
-
GC62300
JC124
JC124 是一种特异性的 NLRP3 炎症小体抑制剂。JC124 具有抗炎和神经保护作用。
-
GC62273
JR14a
JR14a, a selective and potent human Complement C3a receptor antagonist, which is assessed by inhibition of intracellular calcium release (IC50=10 nM) induced in human monocyte-derived macrophages by C3a, inhibition of β-hexosaminidase secretion (IC50=8 nM) from human LAD2 mast cells degranulated by C3a, and selectivity for human C3aR over C5aR.
-
GC62269
RRD-251
(2,4-二氯苯基)甲基硫基甲烷脒盐酸盐
RRD-251 是一种视网膜母细胞瘤肿瘤抑制蛋白 (Rb)-Raf-1相互作用 (Rb-Raf-1 interaction) 的抑制剂,具有高效的抗增殖、抗血管生成和抗肿瘤活性。 -
GC62252
Mefuparib hydrochloride
MPH
Mefuparib hydrochloride (MPH) 是一种具有口服活性的,底物竞争性和选择性的 PARP1/2 抑制剂,IC50 分别为 3.2 nM 和 1.9 nM。Mefuparib hydrochloride 诱导细胞凋亡 (apoptosis),并在体内外具有显着的抗癌活性。 -
GC62246
G5-7
G5-7 is an orally active and allosteric JAK2 inhibitor, selectively inhibits JAK2 mediated phosphorylation and activation of EGFR (Tyr1068) and STAT3 by binding to JAK2.
-
GC62242
Sideroxylin
Sideroxylin 是一种从 Callistemon lanceolatus 中分离的 C-甲基化黄酮,对金黄色葡萄球菌具有抗菌活性。Sideroxylin 可抑制卵巢癌细胞增殖并诱导凋亡 (apoptosis),导致 DNA 断裂,线粒体膜去极化,产生活性氧 (ROS)。
-
GC62224
Ixekizumab
伊西贝单抗; LY2439821
Ixekizumab 是一种人源化 IgG4 单克隆抗体,可选择性结合和中和白细胞介素 IL-17A (KD<3 pM)。Ixekizumab 直接阻断 IL-17A 与 IL-17RA 的结合,但不与其他 IL-17 家族成员结合。Ixekizumab 用于中重度斑块型银屑病的研究。 -
GC62222
DB2313
DB2313 是一种有效的转录因子 PU.1 抑制剂,apoptosis 为 14 nM。DB2313 破坏了 PU.1 与靶基因启动子的相互作用。DB2313 可诱导急性髓细胞性白血病 (AML) 细胞凋亡 (apoptosis),并具有抗癌作用。
-
GC62203
Falcarindiol
法卡林二醇
Falcarindiol (FAD, (3R,8S)-Falcarindiol, FaDOH) is a natural polyacetylene compound found rich in many plants of the Umbelliferae family. Falcarindiol suppresses LPS-stimulated expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β). Falcarindiol attenuates the LPS-induced activation of JNK, ERK, STAT1, and STAT3 signaling molecules. -
GC62198
c-di-AMP sodium
c-di-AMP, Cyclic di-Adenosine monophosphate, 3',5'-Cyclic diadenylic acid, Cyclic diadenylate
C-di-AMP是STING(刺激内质网的蛋白)的激动剂,通过与该跨膜蛋白结合,激活TBK3-IRF3信号通路,进而引发I型IFN和TNF的产生。 -
GC62196
Nisoldipine-d7
尼索地平 d7
Nisoldipine-d7 是 Nisoldipine 的氘代物。Nisoldipine(BAY-k 5552)是高效特异的 L 型 Cav1.2 通道阻断剂,IC50 为 10 nM。 -
GC62193
(1S,2S)-Bortezomib
硼替佐米杂质E
(1S,2S)-Bortezomib 是 Bortezomib 的对映异构体。Bortezomib 是一种细胞渗透性、可逆性和选择性的蛋白酶体抑制剂,通过靶向苏氨酸残基有效抑制 20S 蛋白酶体 (Ki 为 0.6 nM)。Bortezomib 破坏细胞周期、诱导细胞凋亡以及抑制核因子 NF-κB。Bortezomib 是一种抗癌药物,也是第一种用于人类的蛋白酶体抑制剂。 -
GC62192
COG1410
COG1410 是一种载脂蛋白 E 的衍生肽。COG1410 在小鼠颅脑损伤 (TBI) 模型中发挥神经保护和抗炎作用。COG1410 可用于神经系统疾病的研究。
-
GC62191
TD52
A derivative of erlotinib
-
GC62186
KB02-SLF
KB02-SLF 是一种基于 PROTAC 的核 FKBP12 降解剂 (molecular glue)。KB02-SLF 通过共价修饰 DCAF16 (E3 ligase) 促进 FKBP12 降解,并可以提高生物系统中蛋白质降解的持久性。KB02-SLF 由 SLF 与泛素 E3 连接酶配体 (KB02) 通过 linker 连接而成。
-
GC62174
ON1231320
ON1231320 (7ao), an arylsulfonyl pyrido-pyrimidinone, is a highly specific inhibitor of polo like kinase 2 (PLK2). It also blocks tumor cell cycle progression in the G2/M phase in mitosis and causes apoptosis.
-
GC62167
Fluorizoline
Fluorizoline 选择性地直接结合到 prohibitin 1 (PHB1) 和 2 (PHB2),并诱导凋亡。Fluorizoline 通过上调 NOXA 和 BIM 降低慢性淋巴细胞性白血病 (CLL) 细胞的活力。Fluorizoline 以 p53 非依赖性方式发挥抗肿瘤作用。
-
GC62164
BAY1082439
N-[8-[[(2R)-2-羟基-3-(吗啉-4-基)丙基]氧基]-7-甲氧基-2,3-二氢咪唑并[1,2-C]喹唑啉-5-基]-2-甲基吡啶-3-甲酰胺
An inhibitor of PI3Kα, PI3Kβ, and PI3Kδ -
GC62161
HOIPIN-1
JTP-0819958
HOIPIN-1 (JTP-0819958, HOIP inhibitor-1) is a linear ubiquitin chain assembly complex (LUBAC) inhibitor with an IC50 of 2.8 μM for inhibiting the in vitro linear ubiquitination activity of the petit-LUBAC. -
GC62142
WH-4-025
WH-4-025 是盐诱导激酶 (SIK) 的抑制剂 (WO2016023014 A2)。
-
GC62127
OATD-01
An inhibitor of CHIT1 and CHIA
-
GC62125
PD-1/PD-L1-IN-10
PD-1/PD-L1-IN-10 (compound B2) 是具有口服活性的 PD-1/PD-L1 抑制剂 (IC50 of 2.7 nM),具有抗肿瘤活性。
-
GC62111
PND-1186 hydrochloride
VS-4718 hydrochloride; SR-2516 hydrochloride
A potent FAK inhibitor -
GC62104
WM-3835
WM-3835 is a novel and high-specific small molecule Lysine Acetyltransferase 7 (KAT7, MYST2, HBO1) inhibitor, able to potently suppressed OS cell proliferation and migration, and leads to apoptosis activation.
-
GC19824
(±)-Pinocembrin
松属素,(±)-5,7-Dihydroxyflavanone; NSC 43318
A flavonoid with diverse biological activities -
GC19819
Ermanin
堪非醇3,4'-二-O-甲醚
Ermanin 是一种从 Tanacetum microphyllum 中分离出来的类黄酮。 -
GC62040
Cinnamyl-3,4-dihydroxy-α-cyanocinnamate
CDC
Cinnamyl-3,4-dihydroxy-α-cyanocinnamate (CDC) 是一种有效的 12/15 脂氧合酶 (12/15-LO) 抑制剂。Cinnamyl-3,4-dihydroxy-α-cyanocinnamate 可用于研究1型糖尿病。 -
GC62033
3α-Hydroxy pravastatin sodium
3Α-羟基普伐他汀钠
A metabolite of pravastatin -
GC61995
PKCβ inhibitor 1
3-[1-[3-(1H-咪唑-1-基)丙基]-1H-吲哚-3-基]-4-(苯氨基)-1H-吡咯-2,5-二酮
A PKCβ Inhibitor -
GC61993
Kaempferol 3-O-β-D-glucuronide
山奈酚葡萄糖醛酸苷,Kaempferol-3-glucuronide; Kaempferol-3-O-glucuronide
A flavonol glycoside and an active metabolite of kaempferol with diverse biological activities -
GC19792
ALC-0315
ALC-0315 是 COVID-19mRNA 疫苗的关键成分,也是核酸治疗研究中备受追捧的脂质。
-
GC61948
Inecalcitol
伊奈骨化醇,TX 522
Inecalcitol (TX 522) 是一种独特的维生素 D3 类似物,是一种具有口服活性维生素 D 受体 (VDR) 激动剂。Inecalcitol 可诱导细胞凋亡 (apoptosis),并具有有效的抗癌活性。