Angiogenesis
Angiogenesis is the formation and remodelling of new blood vessels and capillaries from growth of pre-existing blood vessels. It normally occurs during wound healing and embryonic development, but is also required for tumour growth and metastasis in cancer.
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BTK inhibitor
Tirabrutinib (ONO-4059) is a highly selective, orally bioavailable BTK inhibitor with an IC50 of 2.2 nM.
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Bruton tyrosine kinase 抑制剂
PCI-32765 (Ibrutinib)是Bruton酪氨酸激酶(BTK)的口服生物利用小分子抑制剂,具有潜在的抗肿瘤活性。对Bmx,CSK,FGR,BRK及HCK适度有效,对EGFR,Yes,ErbB2,JAK3等作用效果较弱。
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- Simonowski A, .et al. Differential use of BTK and PLC in FcεRI- and KIT-mediated mast cell activation: A marginal role of BTK upon KIT activation, Biochim Biophys Acta Mol Cell Res, 2019, Dec 11;1867(4):118622 PMID: 31837347
- Carolin N. Zorn, .et al. Stimulus strength determines the BTK-dependence of the SHIP1-deficient phenotype in IgE/antigen-triggered mast cells, Sci Rep, 2018, 8: 15467 PMID: 30341350
- Li T, .et al. Bruton's tyrosine kinase potentiates ALK signaling and serves as a potential therapeutic target of neuroblastoma, Oncogene, 2018, Nov;37(47):6180-6194 PMID: 30013190
- Brittany M. Duggan, .et al. Tyrosine kinase inhibitors of Ripk2 attenuate bacterial cell wall-mediated lipolysis, inflammation and dysglycemia, Sci Rep, 2017, 7: 1578 PMID: 28484277
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BTK 抑制剂
CGI1746是具有新结合模式的小分子Btk抑制剂化学型,可稳定无活性的非磷酸化酶构象。
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BTK 抑制剂
GDC-0834 Racemate是一种有效且选择性的Bruton酪氨酸激酶(BTK)抑制剂,被研究用作类风湿关节炎的潜在治疗剂。
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Btk 抑制剂
AVL-292是一种高选择性共价Btk抑制剂。
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BTK 抑制剂
CNX-774是有效的Btk抑制剂(IC50 <1 nM)。
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BTK 抑制剂
RN486是一种布鲁顿酪氨酸激酶(Btk)抑制剂。
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BTK 抑制剂
AVL-292 benzenesulfonate是一种共价,高选择性,口服活性的Btk小分子抑制剂,IC50值为0.5 nM,选择性是其他测定激酶的1400倍以上。
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Btk 抑制剂
ACP-196是Bruton酪氨酸激酶(BTK)抑制剂,具有潜在的抗肿瘤活性。它抑制BTK的活性并阻止B细胞抗原受体(BCR)信号传导途径的激活。
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BTK 抑制剂
GDC0853是有效的口服BTK抑制剂。
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BTK 抑制剂
BMS-935177是一种有效的BTK抑制剂,具有多种激酶改善的激酶选择性和优异的口服暴露性。应该在自身免疫性疾病中提供有用的临床疗效。
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Btk 抑制剂
Btk inhibitor 2 是Bruton酪氨酸激酶(BTK)抑制剂。
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BTK 抑制剂
Vecabrutinib是有效的,非共价的,可逆的BTK抑制剂,可抑制BCR途径的信号传导。
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BTK 抑制剂
PF-06250112 is a potent, highly selective, orally bioavailable BTK inhibitor with an IC50 of 0.5 nM, shows inhibitory effect toward BMX nonreceptor tyrosine kinase and TEC with IC50s of 0.9 nM and 1.2 nM, respectively.
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BTK degrader
MT-802 is a potent BTK degrader based on PROTAC technology, with a DC50 of 1 nM. MT-802 has potential to treat C481S mutant chronic lymphocytic leukemia (CLL).
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FAK 抑制剂
PF 573228是一种有效和选择性的粘着斑激酶(FAK)抑制剂(IC50 = 4 nM)。
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- Izumi D, .et al. CXCL12/CXCR4 activation by cancer-associated fibroblasts promotes integrin β1 clustering and invasiveness in gastric cancer, Int J Cancer, 2016, Mar 1;138(5):1207-19 PMID: 26414794
- Aya Yokota-Nakatsuma, .et al. Beta 1-integrin ligation and TLR ligation enhance GM-CSF-induced ALDH1A2 expression in dendritic cells, but differentially regulate their anti-inflammatory properties, Sci Rep, 2016, 6: 37914 PMID: 27897208
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FAK 抑制剂
PF-562271是一种有效的,ATP竞争性的,可逆的FAK抑制剂,作用于FAK比作用于Pyk2选择性高10倍左右,比作用于其他蛋白激酶(除了一些CDKs)选择性高100倍以上。
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- Jiping Yue, .et al. In vivo epidermal migration requires focal adhesion targeting of ACF7, Nat Commun, 2016, 7: 11692 PMID: 27216888
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FAK 抑制剂
PF-04554878 (Defactinib)是一种新型FAK激酶抑制剂,可降低胰腺神经内分泌肿瘤细胞的生长并诱导其凋亡。
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- Shalana O'Brien, .et al. FAK inhibition with small molecule inhibitor Y15 decreases viability, clonogenicity, and cell attachment in thyroid cancer cell lines and synergizes with targeted therapeutics, Oncotarget., 2014, Sep; 5(17): 7945-7959. PMID: 25277206
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FAK 抑制剂
NVP-TAE 226是一种强效FAK抑制剂,IC50为5.5 nM,对pyk2(IC50=3.5 nM)有适度的强效作用;对InsR, IGF-1R, ALK和c-Met的效力降低10-100倍。
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FAK 抑制剂
GSK2256098是一种粘着斑激酶1(FAK)抑制剂,具有潜在的抗血管生成和抗肿瘤活性。
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PTK2/FAK inhibitor
BI-4464 is a highly selective ATP competitive inhibitor of PTK2/FAK, with an IC50 of 17 nM. A PTK2 ligand for PROTAC.
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FAK degrader
PROTAC FAK degrader 1 is a selective and potent focal adhesion kinase (Fak) degrader with an IC50 of 6.5 nM, DC50 of 3 nM.
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FAK inhibitor
Y15 is a potent and specific inhibitor of focal adhesion kinase (FAK) that inhibits its autophosphorylation activity, decreases the viability of cancer cells, and blocks tumor growth.
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FAK inhibitor
Defactinib (VS-6063; PF-04554878) is a novel FAK inhibitor with potential antiangiogenic and antineoplastic activities.
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FAK inhibitor
Defactinib hydrochloride (VS-6063 hydrochloride; PF 04554878 hydrochloride) is a novel FAK inhibitor, which inhibits FAK phosphorylation at the Tyr397 site in a time- and dose-dependent manner.
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FAK/PYK2 抑制剂
PF 431396是一种双粘着斑激酶(FAK)和富含脯氨酸的酪氨酸激酶2(PYK2)抑制剂(IC50值分别为2和11 nM)。
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Aurora A/B Kinase 抑制剂
PF-03814735是一种新颖,有效且可逆的Aurora A/B抑制剂,IC50为0.8 nM/5 nM,对Flt3,FAK,TrkA的效力较低,对Met和FGFR1的活性最低。
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FAK 抑制剂
PF-00562271是PF-562271的苯磺酸盐,是一种有效的,ATP竞争性,可逆的FAK和Pyk2抑制剂,IC50分别为1.5 nM和14 nM。
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FAK 抑制剂
PND-1186是一种强效fak抑制剂,ic50为1.5 nm。
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PYK2/FAK 抑制剂
PF-4618433与原型BIRB796相比,PF-4618433显示出PYK2效价提高、p38活性降低和总体选择性优越。
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Syk 抑制剂
R788 (Fostamatinib)是重要的脾酪氨酸激酶(Syk)抑制剂,显示出对激酶介导的IgG Fcγ受体信号转导的功效。
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- Mahon OR, .et al. Orthopaedic implant materials drive M1 macrophage polarization in a spleen tyrosine kinase- and mitogen-activated protein kinase-dependent manner, Acta Biomater, 2018, Jan;65:426-435 PMID: 29104084
- Emma M. Corr, .et al. Osteoarthritis-associated basic calcium phosphate crystals activate membrane proximal kinases in human innate immune cells, Arthritis Res Ther, 2017, 19: 23 PMID: 28173838
- Cunningham CC, .et al. Intra-articular basic calcium phosphate and monosodium urate crystals inhibit anti-osteoclastogenic cytokine signalling, Osteoarthritis Cartilage, 2016, Dec;24(12):2141-2152 PMID: 27426968
- Corr EM, .et al. Cholesterol crystals activate Syk and PI3 kinase in human macrophages and dendritic cells, Atherosclerosis, 2016, Aug;251:197-205 PMID: 27356299
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Syk 抑制剂
BAY 61-3606是一种细胞可渗透的咪唑并嘧啶化合物,可作为Syk酪氨酸激酶活性的有效,ATP竞争性,可逆和高度选择性抑制剂,而对Btk,Fyn,Itk,Lyn和Src无抑制作用。
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- Ju-Won Jang, .et al. Spleen tyrosine kinase regulates crosstalk of hypoxia-inducible factor-1α and nuclear factor (erythroid-derived2)-like 2 for B cell survival, Int Immunopharmacol, 2021, Mar 21;95:107509 PMID: 33761438
- Sojin Park, .et al. BAFF attenuates oxidative stress-induced cell death by the regulation of mitochondria membrane potential via Syk activation in WiL2-NS B lymphoblasts, Sci Rep, 2020, 10: 11784 PMID: 32678160
- Park S, .et al. Spleen tyrosine kinase-dependent Nrf2 activation regulates oxidative stress-induced cell death in WiL2-NS human B lymphoblasts, Free Radic Res, 2018, Sep 11:1-11 PMID: 30203714
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Syk 抑制剂
P505-15 (PRT062607,BIIB057)是一种新型的,高度选择性的,Syk抑制剂(SYK IC(50)= 1 nM),具有比SYK活性至少高80倍的抗SYK活性。
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- Li T, .et al. Bruton's tyrosine kinase potentiates ALK signaling and serves as a potential therapeutic target of neuroblastoma, Oncogene, 2018, Nov;37(47):6180-6194 PMID: 30013190
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Dual Syk and JAK 抑制剂
PRT 062070 (Cerdulatinib)是一种新型的口服双脾酪氨酸激酶(Syk)和janus激酶(JAK)抑制剂。Cerdulatinib优先抑制各种细胞类型中JAK1和JAK3依赖性细胞因子介导的信号传导和功能性反应。
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Syk 抑制剂
BAY 61-3606 dihydrochloride是一种有效的Syk激酶抑制剂(Ki = 7.5 nM)。
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Syk 抑制剂
PRT-060318是一种新型的酪氨酸激酶Syk选择性抑制剂,可用于HIT治疗。
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Syk 抑制剂
R112是Syk抑制剂。R112抑制了肥大细胞中抗IgE交联诱导的脱颗粒,并阻断了白三烯C4的产生和所有促炎细胞因子的测试。
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ATP-competitive SYK inhibitor
RO9021 is an orally bioavailable, novel ATP-competitive inhibitor of SYK, with an average IC50 of 5.6 nM.
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SYK inhibitor
Lanraplenib (GS-9876) is a highly selective and orally active SYK inhibitor (IC50=9.5 nM) in development for the treatment of inflammatory diseases.
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Syk inhibitor
Fostamatinib disodium hexahydrate (R788 disodium hexahydrate), a prodrug of the active metabolite R406, is a potent Syk inhibitor with IC50 of 41 nM.
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Syk inhibitor
TAK-659 hydrochloride is a potent, selective and orally available spleen tyrosine kinase (Syk) inhibitor with an IC50 of 3.2 nM.
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Syk 抑制剂
R935788 (Fostamatinib disodium,R788)是一种有效的口服Syk抑制剂,可通过阻断抗原依赖性B细胞受体信号传导来抑制CLL的Eμ-TCL1转基因小鼠模型中的肿瘤生长。
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Syk 抑制剂
Piceatannol是一种抗炎,免疫调节和抗增殖剂。抑制p56lck和syk蛋白酪氨酸激酶,并抑制TNF诱导的NF-κB活化和基因表达。
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Syk 抑制剂
GS-9973 (Entospletinib)是一种口服酪氨酸激酶(Syk)抑制剂,具有潜在的抗肿瘤活性。
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Syk 抑制剂
PRT2607,也称为PRT062607,P505-15和BIIB057,是一种新型,高度选择性且口服可生物利用的小分子SYK抑制剂(SYK IC(50)= 1 nM),具有至少80倍的抗SYK活性 大于对其他激酶的亲和力。
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Src/Syk 抑制剂
MNS是Src和Syk酪氨酸激酶的有效和选择性抑制剂。
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SYK/JAK inhibitor
Gusacitinib (ASN-002) is a potent dual inhibitor of spleen tyrosine kinase (SYK) and janus kinase (JAK) with IC50 values of 5-46 nM.
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Syk/PI3K inhibitor
SRX3207 is an orally active and first-in-class dual Syk/PI3K inhibitor, with IC50 values of 10.7 nM and 861 nM for Syk and PI3Kα, respectively. SRX3207 relieves tumor immunosuppression.
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Abl-Src 抑制剂
Dasatinib (BMS-354825)是一种口服多BCR/ABL和Src家族酪氨酸激酶抑制剂。Dasatinib (BMS-354825)的主要靶标是BCR/ABL,Src,c-Kit,ephrin受体和其他几种酪氨酸激酶,但不是erbB激酶,例如EGFR或Her2。
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- Chihiro Motozono, .et al. The SARS-CoV-2 Omicron BA.1 spike G446S mutation potentiates antiviral T-cell recognition, Nat Commun, 2022, Sep 21;13(1):5440 PMID: 36130929
- Aya Hasan Alshammari, .et al. Discrimination of hand-foot skin reaction caused by tyrosine kinase inhibitors based on direct keratinocyte toxicity and vascular endothelial growth factor receptor-2 inhibition, Biochem Pharmacol, 2022, Mar;197:114914 PMID: 35041812
- David E J Klawon, .et al. Altered selection on a single self-ligand promotes susceptibility to organ-specific T cell infiltration, J Exp Med, 2021, Jun 7;218(6) PMID: 33914024
- Reiko Watanabe, .et al. Development of an In Silico Prediction Model for P-glycoprotein Efflux Potential in Brain Capillary Endothelial Cells toward the Prediction of Brain Penetration, J Med Chem, 2021, Mar 11;64(5):2725-2738 PMID: 33619967
- Li Li, .et al. Evidence for activated Lck protein tyrosine kinase as the driver of proliferation in acute myeloid leukemia cell, CTV-1, Leukemia Res, 2019, 78:12-20 PMID: 30660961
- Sano T, .et al. Gliding Basal Cell Migration of the Urothelium during Wound Healing, Am J Pathol, 2018, Nov;188(11):2564-2573 PMID: 30121259
- Ines Peschel, .et al. FLT3 and FLT3-ITD phosphorylate and inactivate the cyclin-dependent kinase inhibitor p27Kip1 in acute myeloid leukemia, Haematologica, 2017, Aug; 102(8): 1378-1389 PMID: 28522571
- Brittany M. Duggan, .et al. Tyrosine kinase inhibitors of Ripk2 attenuate bacterial cell wall-mediated lipolysis, inflammation and dysglycemia, Sci Rep, 2017, 7: 1578 PMID: 28484277
- John D. Leonard, .et al. Identification of natural regulatory T cell epitopes reveals convergence on a dominant autoantigen, Immunity, 2017, Jul 18; 47(1): 107-117.e8 PMID: 28709804
- Fujita KI, .et al. Involvement of the Transporters P-Glycoprotein and Breast Cancer Resistance Protein in Dermal Distribution of the Multikinase Inhibitor Regorafenib and Its Active Metabolites, J Pharm Sci, 2017, Sep;106(9):2632-2641 PMID: 28479358
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Src/Abl 抑制剂
Saracatinib (AZD0530)是一种高选择性,双特异性Src/Abl激酶抑制剂,对c-Src和Abl激酶的IC50分别为2.7和30 nM。
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- Andromachi Lambrianidou, .et al. mTORC2 deploys the mRNA binding protein IGF2BP1 to regulate c-MYC expression and promote cell survival, Cell Signal, 2021, Apr;80:109912 PMID: 33388443
- Chisato Naito, .et al. Facilitatory effects of fetuin-A on atherosclerosis, Atherosclerosis, 2016, Mar;246:344-51 PMID: 26828753
- Kenta Maruyama, .et al. 5-Azacytidine-induced Protein 2 (AZI2) Regulates Bone Mass by Fine-tuning Osteoclast Survival, J Biol Chem, 2015, Apr 10; 290(15): 9377-9386 PMID: 25691576
- Amanda L Jackson, .et al. Emerging therapies: angiogenesis inhibitors for ovarian cancer, Expert Opin Emerg Drugs, 2015, Jun;20(2):331-46 PMID: 26001052