阿拉丁小分子抑制剂、激动剂、拮抗剂--血管生成信号通路(上)

阿拉丁小分子抑制剂、激动剂、拮抗剂--血管生成信号通路(上)
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阿拉丁小分子抑制剂、激动剂、拮抗剂--血管生成信号通路(上)

血管生成

血管生成,即从已存在的血管中生成新血管。此通路是通过人体中存在的诸多互补和复杂的信号途径调节的。正常情况下,血管生成的相关诱导剂和抑制剂之间保持平衡状态。但对于创伤、缺氧或炎症继发等微环境破坏的条件下,此通路能做出迅速的应答。在各种慢性病理和肿瘤的情况下,血管生成的平衡状态被打破,导致异常的血管生成或新生血管。

血管生成信号通路转导过程

血管生成的激活导致促血管生成生长因子(VEGF、PDGF、FGF和TGF等)的释放,这些因子将其受体结合到已有血管内的内皮细胞上,从而诱导PI3K/Akt、Erk1/2、Smad和Notch等多种途径的信号转导,引起内皮细胞增殖和迁移。内皮细胞利用基质金属蛋白酶和整合素来消化细胞外基质,迁移到新的区域,在那里它们延长并形成管子,产生新的血管。
在肿瘤血管生成过程中,癌细胞刺激新血管的形成,为肿瘤输送氧气和营养。随着肿瘤的生长,位于肿瘤中心的细胞缺氧,使得转录因子HIF-1α(缺氧诱导因子-1)稳定表达。该转录因子与HIF-1β结合上调几种促血管生成基因的表达。此外,生长因子信号还刺激HIF-1活性,以维持生长细胞的氧稳态。

血管生成信号通路图

产品列表

   *FLT

项目号产品名称规格CAS包装细胞靶点IC50Ki
S129593 Sorafenib Tosylate ≥99% 475207-59-1 50mg,100mg,250mg,1g,5g 无细胞 Raf-1 6 nM
B-Raf 22 nM
VEGFR-2 90 nM
VEGFR-3 20 nM
PDGFR-β 57 nM
Flt-3 59 nM
c-KIT 68 nM
T127762 Tozasertib ≥98% 639089-54-6 25mg,100mg FLT3 30 nM
S125267 SP600125 ≥98% 129-56-6 25mg,100mg,500mg,1g,5g 无细胞 JNK1 40 nM
JNK2 40 nM
JNK3 90 nM
F127011 Foretinib (GSK1363089) ≥98% 849217-64-7 5mg,25mg,100mg 无细胞 Met 0.4 nM  
KDR 0.9 nM  
Q127558 Quizartinib (AC220) ≥99% 950769-58-1 5mg,10mg,50mg,500mg MV4-11 Flt3(ITD) 1.1 nM/4.2 nM  
 RS4;11 Flt3(WT) 1.1 nM/4.2 nM  
D126778 Dovitinib (TKI-258, CHIR-258) ≥99% 405169-16-6 10mg,50mg,250mg 无细胞 FLT3 1 nM  
c-Kit 2 nM  
T126330 Fedratinib (SAR302503, TG101348) ≥98% 936091-26-8 5mg,25mg,100mg 无细胞 JAK2 3 nM  
L126993 Linifanib (ABT-869) ≥99% 796967-16-3 5mg,10mg,50mg KDR 4 nM  
CSF-1R 3 nM  
Flt-1/3 3 nM/4 nM  
PDGFRβ 66 nM  
C127776 Crenolanib (CP-868596) ≥99% 670220-88-9 5mg,10mg,50mg PDGFRα 2.1 nM  
PDGFRβ 3.2 nM  
R129910 R406 (free base) ≥99% 841290-80-0 5mg,10mg,25mg,50mg,100mg   Syk 41 nM  
M127412 Amuvatinib (MP-470) ≥98% 850879-09-3 5mg,25mg,100mg c-Kit 10 nM  
PDGFα 40 nM  
Flt3 81 nM  
T125150 Tandutinib (MLN518) ≥98% 387867-13-2 25mg,100mg,500mg   FLT3 0.22 μM  
T127523 TG101209 98% 936091-14-4 5mg,25mg,100mg 无细胞 JAK2 6 nM  
Flt3 25 nM  
RET 17 nM  
K127169 KW-2449 ≥98% 1000669-72-6 5mg,25mg,100mg   Flt3 6.6 nM  
E126318 ENMD-2076 ≥99% 934353-76-1 5mg,10mg,50mg Aurora A 14 nM  
Flt3 1.86 nM  
L127618 LDK378 ≥99% 1032900-25-6 5mg,25mg,100mg,250mg 无细胞 ALK 0.2 nM  
IGF-1R 8 nM  
InsR 7 nM  
STK22D 23 nM  
FLT3 60 nM  
P129908 PRT062607 (P505-15, BIIB057) HCl ≥98% 1370261-97-4 5mg,25mg 无细胞 Syk 1 nM  
S125098 Sorafenib ≥99% 284461-73-0 250mg,1g 无细胞 Raf-1 6 nM  
B-Raf 22 nM  
VEGFR-2 90 nM  
VEGFR-3 20 nM  
PDGFR-β 57 nM  
Flt-3 59 nM  
c-KIT 68 nM  
C129757 Cabozantinib malate (XL184) ≥99% 1140909-48-3 10mg,25mg,50mg,100mg,250mg VEGFR2 0.035 nM  
无细胞 c-Met 1.3 nM  
Ret 4 nM  
Kit 4.6 nM  
Flt-1/3/4 12 nM/11.3 nM/6 nM  
Tie2 14.3 nM  
AXL 7 nM  
T129806 TCS 359 ≥99% 301305-73-7 10mg,25mg,50mg   FLT3 43 nM
E129946 ENMD-2076 L-(+)-Tartaric acid ≥99% 1291074-87-7 5mg,25mg Aurora A 14 nM
VEGFR(Flt3) 1.86 nM
L127298 LY2801653 - 1206799-15-6 5mg,10mg,50mg   MET 2 nM
C168062 Crotonoside 95% (HPLC) 1818-71-9 5mg,10mg,25mg FLT3
HDAC3/6
G172979 Gilteritinib 97% 1254053-43-4 5mg,100mg FLT3 0.29 nM
AXL 0.73 nM
P171724 Pexidartinib 97% 1029044-16-3 5mg,100mg CSF-1R 20 nM
Kit 10 nM
FLT3 160 nM  

 

*DNA alkylator

项目号产品名称规格CAS包装细胞靶点IC50EC50Ki
S129593 Sorafenib Tosylate ≥99% 475207-59-1 10mg,50mg,250mg,1g,5g 无细胞 Raf-1 6 nM
B-Raf 22 nM
VEGFR-2 90 nM
VEGFR-3 20 nM
PDGFR-β 57 nM
Flt-3 59 nM
c-KIT 68 nM
E129728 Sunitinib Malate ≥99% 341031-54-7 100mg,500mg,1g 无细胞 VEGFR2 (Flk-1) 80 nM
PDGFRβ 2 nM
L125046 Lenalidomide ≥99% 191732-72-6 50mg,250mg,1g,5g PBMCs TNF-α 13 nM
C126195 Cabozantinib (XL184, BMS-907351) ≥98% 849217-68-1 5mg,10mg,50mg,100mg,250mg 无细胞 VEGFR2 0.035 nM
c-Met 1.3 nM
 Ret 4 nM
Kit 4.6 nM
Flt-1/3/4 12 nM/11.3 nM/6 nM
Tie2 14.3 nM
AXL 7 nM
P127550 Ponatinib (AP24534) ≥99% 943319-70-8 10mg,50mg,250mg 无细胞 Abl 0.37 nM
PDGFRα 1.1 nM
VEGFR2 1.5 nM
FGFR1 2.2 nM
Src 5.4 nM
K125585 Ki20227 ≥98% 623142-96-1 10mg,50mg KDR 2 nM
VEGFR-2 12 nM
c-Kit 451 nM
PDGFRβ 217 nM
A129732 Axitinib ≥99% 319460-85-0 10mg,50mg,250mg,1g 猪主动脉内皮细胞 VEGFR1 0.1 nM
VEGFR2 0.2 nM
VEGFR3 0.1-0.3 nM
PDGFRβ 1.6 nM
c-Kit 1.7 nM
F127011 Foretinib (GSK1363089) ≥98% 849217-64-7 5mg,25mg,100mg 无细胞 Met 0.4 nM
KDR 0.9 nM
N129725 Nintedanib (BIBF 1120) ≥98% 656247-17-5 5mg,10mg,25mg,50mg,100mg,500mg 无细胞 VEGFR1 34 nM
VEGFR2 13 nM
VEGFR3 13 nM
FGFR1 69 nM
FGFR2 37 nM
FGFR3 108 nM
PDGFRα 59 nM
PDGFRβ 65 nM
V125180 Vandetanib (ZD6474) ≥99% 443913-73-3 25mg,100mg,500mg 无细胞 VEGFR2 40 nM
VEGFR3 110 nM
EGFR 500 nM
R127804 Regorafenib (BAY 73-4506) ≥99% 755037-03-7 5mg,10mg,25mg,100mg 无细胞 VEGFR1 13 nM
VEGFR2 4.2 nM
VEGFR3 46 nM
PDGFR-β 22 nM
Kit 7 nM
RET 1.5 nM
Raf-1 2.5 nM
P129722 Pazopanib HCl (GW786034 HCl) ≥98% 635702-64-6 25mg,100mg,250mg,1g 无细胞 VEGFR1 10 nM
VEGFR2 30 nM
VEGFR3 47 nM
PDGFR 84 nM
FGFR 74 nM
c-Kit 140 nM
c-fms 146 nM
C125911 Cediranib ≥98% 288383-20-0 10mg,50mg VEGFR(KDR) <1 nM
Flt1/4 5 nM/≤3 nM
P125865 PD173074 ≥99% 219580-11-7 5mg,10mg,50mg FGFR1 25 nM
VEGFR2 100-200 nM
D126778 Dovitinib (TKI-258, CHIR-258) ≥99% 405169-16-6 10mg,50mg,250mg 无细胞 FLT3 1 nM
c-Kit 2 nM
L126993 Linifanib (ABT-869) ≥99% 796967-16-3 5mg,10mg,50mg KDR 4 nM
CSF-1R 3 nM
Flt-1/3 3 nM/4 nM
PDGFRβ 66 nM
V125857 Vatalanib (PTK787) 2HCl ≥99% 212141-51-0 10mg,50mg 无细胞 VEGFR2/KDR 37 nM
R127906 RAF265 (CHIR-265) ≥98% 927880-90-8 1mg,5mg,10mg,50mg VEGFR2 30 nM
B-Raf 3-60 nM
T126012 Tivozanib (AV-951) ≥98% 475108-18-0 5mg,25mg,100mg VEGFR1 0.21 nM
VEGFR2 0.16 nM
VEGFR3 0.24 nM
M129736 Motesanib Diphosphate (AMG-706) ≥98% 857876-30-3 5mg,10mg,50mg VEGFR1 2 nM
VEGFR2 3 nM
VEGFR3 6 nM
L125518 Lenvatinib (E7080) ≥99% 417716-92-8 5mg,10mg,50mg,100mg VEGFR2(KDR) 4 nM
VEGFR3(Flt-4) 5.2 nM
B127317 Brivanib (BMS-540215) ≥98% 649735-46-6 5mg,10mg,50mg   VEGFR2 25 nM
M127064 MGCD-265 ≥98% 875337-44-3 1mg,5mg,10mg,50mg c-Met 1 nM
VEGFR1/2/3 3 nM/3 nM/4 nM
A126830 AEE788 (NVP-AEE788) ≥97% 497839-62-0 5mg,25mg,100mg EGFR 2 nM
HER2/ErbB2 6 nM
E126318 ENMD-2076 ≥99% 934353-76-1 5mg,10mg,50mg Aurora A 14 nM
Flt3 1.86 nM
O126155 OSI-930 ≥99% 728033-96-3 1mg,5mg,25mg,50mg Kit 80 nM
KDR 9 nM
CSF-1R 15 nM
C126929 CYC116 ≥99% 693228-63-6 1mg,10mg,50mg Aurora A 8.0 nM
Aurora B 9.2 nM
VEGFR2 44 nM
K125876 Ki8751 ≥98% 228559-41-9 5mg,25mg,100mg   VEGFR2 0.9 nM
T129747 Telatinib ≥99% 332012-40-5 1mg,5mg,10mg,50mg VEGFR2/3 6 nM/4 nM
c-Kit 1 nM
PDGFRα 15 nM
P126419 PP121 ≥98% 1092788-83-4 10mg,50mg PDGFR 2 nM
Hck 8 nM
mTOR 10 nM
VEGFR2 12 nM
Src 14 nM
Abl 18 nM
DNA-PK 60 nM
P125184 Pazopanib ≥99% 444731-52-6 25mg,100mg,500mg GFR1 10 nM
VEGFR2 30 nM
VEGFR3 47 nM
PDGFR 84 nM
FGFR 74 nM
c-Kit 140 nM
c-Fms/CSF1R 146 nM
K125907 KRN-633 ≥97% 286370-15-8 5mg,25mg,100mg VEGFR1 170 nM
VEGFR2 160 nM
VEGFR3 125 nM
S126571 SAR131675 ≥99% 1433953-83-3 1mg,10mg,50mg   VEGFR3 23 nM 12 nM
B129768 BMS-794833 ≥99% 1174046-72-0 1mg,5mg,10mg,50mg Met 1.7 nM
VEGFR2 15 nM
S125098 Sorafenib ≥99% 284461-73-0 250mg,1g 无细胞 Raf-1 6 nM
B-Raf 22 nM
VEGFR-2 90 nM
VEGFR-3 20 nM
PDGFR-β 57 nM
Flt-3 59 nM
c-KIT 68 nM
C129757 Cabozantinib malate (XL184) ≥99% 1140909-48-3 10mg,25mg,50mg,100mg,250mg VEGFR2 0.035 nM
c-Met 1.3 nM
Ret 4 nM
Kit 4.6 nM
Flt-1/3/4 12 nM/11.3 nM/6 nM
Tie2 14.3 nM
AXL 7 nM
B129764 Brivanib Alaninate (BMS-582664) ≥95% 649735-63-7 10mg,50mg VEGFR2 25 nM
E126304 Golvatinib (E7050) ≥99% 928037-13-2 1mg,5mg,10mg,50mg c-Met 14 nM
VEGFR-2 16 nM
Z129748 ZM 306416 ≥98% 690206-97-4 10mg,50mg VEGFR1 0.33 μM
EGFR <10 nM
Z129761 ZM 323881 HCl ≥99% 193000-39-4 1mg,10mg,50mg   VEGFR2 <2 nM
E129946 ENMD-2076 L-(+)-Tartaric acid ≥99% 1291074-87-7 5mg,25mg Aurora A 14 nM
VEGFR(Flt3) 1.86 nM
L126507 LY2874455 ≥99% 1254473-64-7 5mg,10mg,50mg FGFR1 2.8 nM
FGFR2 2.6 nM
FGFR3 6.4 nM
FGFR4 6 nM
VEGFR2 7 nM
S167823 SU1498 98% (HPLC) 168835-82-3 5mg,25mg KDR 0.7 μM
D126474 DCC-2618 - 1225278-16-9 5mg,10mg,50mg  
S126061 苏尼替尼 0.99 557795-19-4 100mg,500mg,1g,5g,25g VEGFR2(Flk-1) 80 nM
PDGFRβ 2 nM
D167318 2-D08 98% (HPLC) 144707-18-6 5mg,25mg Axl 0.49 nM
IRAK4 3.9 nM
ROS1 5.3 nM
MLK4 9.8 nM
GSK3β 11 nM
RET 11 nM
KDR 17 nM
PI3Kα 35 nM

 

*BTK

产品号产品名称规格CAS包装靶点IC50
P127143 Ibrutinib (PCI-32765) ≥98% 936563-96-1 5mg,10mg,50mg,250mg BTK 0.5 nM
A127694 AVL-292 98% 1202757-89-8 5mg,10mg,50mg,100mg BTK 0.5 nM
O173511 Olmutinib 97% 1353550-13-6 5mg,100mg    

 

*PDGFR

KDR0.86 nM

产品号产品名称规格CAS包装细胞靶点IC50
S129593 Sorafenib Tosylate ≥99% 475207-59-1 50mg,100mg,250mg,1g,5g 无细胞 Raf-1 6 nM
VEGFR2/Flk1 15 nM
无细胞 B-Raf 22 nM
B-Raf (V599E) 38 nM
PDGFRβ 57 nM
mPDGFRβ 57 nM
FLT3 58 nM
c-Kit 68 nM
VEGFR2 90 nM
FGFR1 580 nM
I129225 Imatinib Mesylate (STI571) ≥99% 220127-57-1 100mg,250mg,1g,5g,25g 无细胞 PDGFR 100 nM
c-Kit 100 nM
v-Abl 600 nM
E129728 Sunitinib Malate ≥99% 341031-54-7 100mg,500mg,1g 无细胞 PDGFRβ  2 nM
VEGFR2 80 nM
FLT3
Kit 
P127550 Ponatinib (AP24534) ≥99% 943319-70-8 10mg,250mg,50mg 无细胞 Abl 0.37 nM
PDGFRα 1.1 nM
VEGFR2 1.5 nM
FGFR1 2.2 nM
c-Src 5.4 nM
c-Kit 12.5 nM
A129732 Axitinib ≥99% 319460-85-0 10mg,250mg,50mg,1g VEGFR1/FLT1 0.1 nM
VEGFR2/Flk1 0.18 nM
VEGFR2/KDR 0.2 nM
VEGFR3 0.1 nM-0.3 nM
PDGFRβ 1.6 nM
Kit 1.7 nM
PDGFRα 5.0 nM 
I124963 Imatinib (STI571) ≥99% 152459-95-5 1g,5g,25g,250mg PDGFR 100 nM
c-Kit 100 nM
v-Abl 600 nM
F127011 Foretinib (GSK1363089) ≥99% 849217-64-7 5mg,100mg,25mg 无细胞 Met 0.4 nM
  Tie-2 1.1 nM
VEGFR3/FLT4 2.8 nM
RON 3 nM
FLT3 3.6 nM
PDGFRα 3.6 nM
Kit 6.7 nM
VEGFR1/FLT1 6.8 nM
PDGFRβ 9.6 nM

 

*Src

项目号产品名称规格CAS包装细胞靶点IC50
D125110 Dasatinib ≥99% 302962-49-8 25mg,100mg,500mg,1g,5g 无细胞 Abl  0.6 nM
Src 0.8 nM
c-Kit (D816V) 37 nM
c-Kit (wt) 79 nM
P127550 Ponatinib (AP24534) ≥99% 943319-70-8 10mg,50mg,250mg 无细胞 Abl 0.37 nM
PDGFRα 1.1 nM
VEGFR2 1.5 nM
FGFR1 2.2 nM
c-Src 5.4 nM
c-Kit 12.5 nM
B129905 Bosutinib (SKI-606) ≥99% 380843-75-4 10mg,50mg,100mg S6 kinase 
ERK 
STAT3 
无细胞 Abl 1 nM
Src 1.2 nM
P125444 Pelitinib ≥98% 257933-82-7 5mg,25mg,100mg EGFR 38.5 nM
Src 282 nM
MEK/ERK 800 nM
ErbB2  1.255 μM
Raf  3.353 μM
K126255 KX2-391 ≥99% 897016-82-9 1mg,5mg,10mg,50mg Src (HuH7) 9 nM
Src (PLC/PRF/5) 13 nM
Src (Hep 3B) 26 nM
Src (Hep G2) 60 nM
N127928 NVP-BHG712 ≥98% 940310-85-0 5mg,25mg,100mg EphB4 25 nM(ED50)
C-Raf 0.395 μM
c-Src 1.266 μM
c-Abl 1.667 μM
E126318 ENMD-2076 ≥99% 934353-76-1 5mg,10mg,50mg FLT3 1.86 nM
RET 10.4 nM
Aurora A 14 nM
VEGFR3/FLT4 15.9 nM
Src 20.2 nM
NTRK1/TRKA 24.2 nM 
CSF-1R/c-Fms 24.8 nM
LCK 43.7 nM
FAK 54.9 nM
PDGFRα 56.4 nM
VEGFR2/KDR 58.2 nM
BLK 69.4 nM
FGFR2 70.8 nM
YES1 78.4 nM
Abl1 (T315I) 81.3 nM
FGFR1 92.7 nM
Fyn 112 nM
JAK2 120 nM
Kit 120 nM
Aurora B 350 nM
P129908 PRT062607 (P505-15, BIIB057) HCl ≥98% 1370261-97-4 5mg,25mg, 无细胞 Syk 1 nM
FGR 81 nM
MLK1 88 nM
PYK2 108 nM
YES 123 nM
FLT3 139 nM
PAK5 166 nM
Lyn 192 nM
cSRC 244 nM
LCK 249 nM
FAK 415 nM
P125361 PP2 ≥98% 172889-27-9 5mg,25mg,100mg 无细胞 LCK 4 nM
Fyn 5 nM
P126419 PP121 ≥98% 1092788-83-4 10mg,50mg PDGFR 2 nM
Hck 8 nM
VEGFR 12 nM
mTOR 13 nM
Src 14 nM
Abl 18 nM
p110α 52 nM
DNA-PK 60 nM
p110δ 150 nM
EphB4 190 nM
Q111274 槲皮素 95.00% 117-39-5 1g,10g,50g,250g Sirtuin  
Src  
PKC  
PI3Kγ 2.4 μM
PI3Kδ 3.0 μM
PI3Kβ 5.4 μM
Q111273 槲皮素 分析标准品,≥98.5% 117-39-5 20mg Sirtuin  
Src  
PKC  
PI3Kγ 2.4 μM
PI3Kδ 3.0 μM
PI3Kβ 5.4 μM

 

*Syk

项目号产品名称规格CAS包装细胞靶点IC50
R129913 R788 (Fostamatinib) Disodium ≥98% 1025687-58-4 50mg,1mg,5mg,10mg 无细胞 Syk 41 nM
R129910 R406 (free base) ≥99% 841290-80-0 25mg,50mg,100mg,5mg,10mg 无细胞 Syk 41 nM
FLT3
P129908 PRT062607 (P505-15, BIIB057) HCl ≥98% 1370261-97-4 5mg,25mg 无细胞 Syk 1 nM 
FGR 81 nM 
MLK1 88 nM
PYK2 108 nM
YES 123 nM 
FLT3 139 nM 
PAK5 166 nM 
Lyn 192 nM
cSRC 244 nM
LCK 249 nM
FAK 415 nM
F129915 Fostamatinib (R788) ≥98% 901119-35-5  50mg,5mg,10mg Syk 41 nM
Adenosine A3 receptor  81 nM
Adenosine transporter 1.84 μM
Monoamine transporter 2.74 μM

 

*VDA

项目号产品名称规格CAS包装细胞靶点IC50Ki
D129922 DMXAA (Vadimezan) ≥98%  117570-53-3  5mg,25mg,100mg,250mg 无细胞 DT-diaphorase 62.5 μM 20 μM
P126141 Plinabulin (NPI-2358) ≥97% 714272-27-2 5mg,10mg,50mg,1g 肿瘤细胞
Tubulin
9.8~18 nM
V129759  Verteporfin ≥97% 129497-78-5 25mg,50mg,1mg,5mg,10mg  
VDA
YAP/TEAD interaction    
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