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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DUB/Bcr/ABL 抑制剂
WP1130 (Degrasyn)是一种新型的选择性小分子去泛素酶抑制剂和Bcr/Abl破坏途径激活剂,可特异性和快速下调野生型和突变型Bcr/Abl蛋白,而不会影响慢性粒细胞性白血病(CML)中的bcr/abl基因表达细胞。
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Bcr-Abl 抑制剂
GNF 2是一种Bcr-abl抑制剂,在表达Bcr-abl的细胞中抑制增殖并诱导凋亡。
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Bcr-Abl 抑制剂
PD-173955是src酪氨酸激酶抑制剂。PD173955抑制Bcr-Abl依赖的细胞生长。PD173955显示G(1)中的细胞周期停滞。PD173955在Bcr-Abl的激酶抑制测定中的IC(50)为1-2 nM,在细胞生长测定中,其抑制Bcr-Abl依赖性底物酪氨酸磷酸化。 PD173955抑制试剂盒配体依赖性c-kit自磷酸化(IC(50)=约25 nM)和试剂盒配体依赖性M07e细胞增殖(IC(50)= 40 nM),但对白介素3依赖性(IC (50)= 250 nM)或粒细胞巨噬细胞集落刺激因子(IC(50)= 1 microM)依赖性细胞生长。
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Bcr-Abl 抑制剂
GNF-5是BCR-ABL的选择性变构抑制剂。
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Bcr-Abl 抑制剂
NRC-AN-019是Bcr-Abl蛋白-酪氨酸激酶的口服酪氨酸激酶抑制剂(TKI)。NRC-AN-019在抑制MDAMB231和HTB20/BT474细胞的血管生成潜力和增殖方面更有效。
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Bcr-Abl 抑制剂
Nilotinib monohydrochloride monohydrate是一种Bcr-Abl抑制剂,IC50小于30 nM。
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Bcr-Abl tyrosine 抑制剂?
Radotinib是一种新型的选择性Bcl-Abl酪氨酸激酶抑制剂。
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Bcr-Abl 抑制剂
GZD824是一种新型的口服生物利用型抑制剂,可抵抗包括T315I在内的各种Bcr-Abl突变体。
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Bcr-Abl 抑制剂
GNF-7是一种有效的II型激酶Bcr-Abl抑制剂,对于M351T,T315I,E255 V,G250E和c-Abl,IC50分别<5 nM,61 nM,122 nM,136 nM和133 nM。
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Bcr-Abl 抑制剂
GZD824 Dimesylate是Bcr-Abl(WT)和Bcr-Abl(T315I)的新型生物可用Bcr-Abl抑制剂,IC50分别为0.34 nM和0.68 nM。
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c-ABL activitor
DPH是一种有效的细胞渗透性c-Abl激活剂,在刺激c-Abl激活中显示出强大的酶和细胞活性。
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dual Bcr-Abl/Lyn 抑制剂
Lyn-IN-1是一种有效的选择性Bcr-Abl/Lyn双重抑制剂,摘自专利WO2014169128A1。
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dual PI3K and BCR-ABL 抑制剂
ON 146040是第一个靶向STAT3和STAT5途径的PI3K和BCR-ABL双重抑制剂;抑制PI3Kα/δ同工型,IC50为14/20 nM。
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ABL inhibitor
SNIPER(ABL)-062, in which an ABL inhibitor is linked to a ligand of cIAP1 via a linker containing a variable polyethylene glycol (PEG) unit, shows a potent activity to degrade the BCR-ABL protein.
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ABL inhibitor
CZC-8004 is a pan-kinase inhibitor and binds a range of tyrosine kinases, including ABL kinase.
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ABL2 inhibitor
CHMFL-ABL-121 is a highly potent type II ABL kinase inhibitor with IC50s of 2 nM and 0.2 nM against purified inactive ABL wt and T315I kinase protein, respectively.
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BCR-ABL inhibitor
CHMFL-ABL-039 is a type II native ABL kinase and drug-resistant V299L mutant BCR-ABL inhibitor with the IC50s of 7.9 nM and 27.9 nM, respectively. CHMFL-ABL-039 is used in the research of chronic myeloid leukemia.
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BCR-ABL inhibitor
BCR-ABL-IN-1 is an inhibitor of BCR-ABL tyrosine kinase, with a pIC50 of 6.46, and may be used in the research of chronic myelogenous leukemia.
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ABL/c-KIT dual kinase inhibitor
CHMFL-ABL/KIT-155 (CHMFL-ABL-KIT-155; compound 34) is a highly potent and orally active type II ABL/c-KIT dual kinase inhibitor.
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Src/c-Abl inhibitor
1-Naphthyl PP1 hydrochloride is a selective inhibitor of src family kinases v-Src and c-Fyn as well as the tyrosine kinase c-Abl (IC50 values are 1.0, 0.6, 0.6, 18 and 22 μM for v-Src, c-Fyn, c-Abl, CDK2 and CAMK II respectively).
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inhibitor of BCR-ABL1 tyrosine kinase
BCR-ABL-IN-2 is an inhibitor of BCR-ABL1 tyrosine kinase, with IC50s of 57 nM, 773 nm for ABL1native and ABL1T315I, respectively.
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Aurora/JAK 抑制剂
AT9283抑制极光激酶A和B,并靶向与骨髓细胞增殖相关的其他酪氨酸和丝氨酸/苏氨酸激酶。
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- Tomoya Takeda, .et al. AT9283 exhibits antiproliferative effect on tyrosine kinase inhibitor-sensitive and -resistant chronic myeloid leukemia cells by inhibition of Aurora A and Aurora B, Oncol Rep, 2020, August 18
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EphB4 抑制剂
NVP-BHG712是EphB4激酶的选择性抑制剂,在体外对EphB4的选择性超过40多种其他激酶(包括FGFR3)。
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- Y Kaibori, .et al. EphA2 phosphorylation at Ser897 by the Cdk1/MEK/ERK/RSK pathway regulates M-phase progression via maintenance of cortical rigidity, the FASEB Journal, 2019, Jan 22:fj201801519RR PMID: 30668924
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Bcr-Abl 抑制剂
DCC-2036 (Rebastinib)是一种Bcr-Abl抑制剂,作用于Abl1(WT)和Abl1(T315I),IC50分别为0.8 nM和4 nM,也抑制SRC, LYN, FGR, HCK, KDR, FLT3,和Tie-2,对c-Kit具有低的抑制活性。
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- Hirosumi Tamura, .et al. Evaluation of anticancer agents using patient-derived tumor organoids characteristically similar to source tissues, Oncol Rep, 2018, Aug; 40(2): 635-646 PMID: 29917168
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Dasatinib Monohydrate是一种新型,有效且多靶点的抑制剂,靶向Abl,Src和c-Kit,IC50分别<1 nM,0.8 nM和79 nM。
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- Izumi-Nakaseko H, .et al. Dasatinib can Impair Left Ventricular Mechanical Function But May Lack Proarrhythmic Effect: A Proposal of Non-clinical Guidance for Predicting Clinical Cardiovascular Adverse Events of Tyrosine Kinase Inhibitors, Cardiovasc Toxicol, 2019, Jul 6 PMID: 31280457
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Bcr-Abl 抑制剂
Nilotinib (AMN-107)是一种Bcr-Abl抑制剂,IC50小于30 nM。
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- Rami Shinnawi, .et al. Monitoring Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes with Genetically Encoded Calcium and Voltage Fluorescent Reporters, Stem Cell Reports, 2015, Oct 13; 5(4): 582-596 PMID: 26372632
- Tetsuya Saita, .et al. Preparation of Antibodies and Development of an Enzyme-Linked Immunosorbent Assay for the Tyrosine Kinase Inhibitors Lapatinib and Nilotinib., Biol Pharm Bull. , 2015, 38(10):1652-7 PMID: 26424026
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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
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Bcr-Abl 抑制剂
Bafetinib (INNO-406)是一种双重Bcr-Abl/Lyn酪氨酸激酶抑制剂。
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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
- S. Dallari, .et al. Src family kinases Fyn and Lyn are constitutively activated and mediate plasmacytoid dendritic cell responses, Nat Commun, 2017, 8: 14830 PMID: 28368000
- Andrea Haerzschel, .et al. BCR and chemokine responses upon anti-IgM and anti-IgD stimulation in chronic lymphocytic leukaemia, Ann Hematol, 2016, 95(12): 1979-1988 PMID: 27542958
- Magdalena Winiarska, .et al. Inhibitors of SRC kinases impair antitumor activity of anti-CD20 monoclonal antibodies, MAbs., 2014, 6(5): 1300-1313. PMID: 25517315
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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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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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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
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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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
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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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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