IGF-1R
信号通路图
研究领域
抑制剂选择性比较
IGF-1R产品
| 产品目录 | 产品描述 | 文献引用 | 实验数据 |
|---|---|---|---|
| S1091 |
Linsitinib (OSI-906)Linsitinib (OSI-906)是一种选择性IGF-1R抑制剂，在无细胞试验中IC50为35 nM；对InsR抑制作用适中，IC50为75 nM，对Abl，ALK，BTK，EGFR， FGFR1/2，PKA等没有抑制活性。Phase 3。 |
(e) c-peptide from these mice 240 min after respective treatments.
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| S1034 |
NVP-AEW541NVP-AEW541是一种有效的IGF-1R/InsR抑制剂，在无细胞试验中IC50为150 nM/140 nM，在细胞试验中对IGF-1R具有较高的作用和选择性。 |
(A) KRAS mutant (SW837 and LoVo) or KRAS/PIK3CA mutant (HCT-116) colorectal cancers were treated with the indicated compounds for 6 hours (gef, gefitinib 1 μM; NVP, NVP-AEW541 1 μM; PHA, PHA-665752 1 μM), and the resulting protein lysates were immunoprecipitated with an anti-p85 antibody. The precipitated proteins were analyzed by Western blots with the indicated antibodies. Whole cell extracts were probed with the indicated antibodies. Asterisks indicate the IRS proteins for SW837 and HCT-116 cells, and ERBB3 for LoVo cells. (B) SW837 cells were grown in either normal serum (5% FBS) or low serum (0.5% FBS) and treated with vehicle, R1507 anti–IGF-IR antibody (25 μg/ml), or NVP-AEW541 (1 μM) for 6 hours. The cells were lysed and probed with the indicated antibodies. |
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| S1093 |
GSK1904529AGSK1904529A是一种选择性的IGF-1R和IR抑制剂，无细胞试验中IC50分别为27 nM和25 nM，作用于IGF-1R/InsR比作用于Akt1/2/， Aurora A/B，B-Raf， CDK2， EGFR等选择性高100倍以上。 |
(E) The level of migration ability of HEC-1B cells treated with insulin, GSK1904529A, and the silencing of DHCR24 was determined using a transwell assay. (F) The invasion ability of HEC-1B cells treated with insulin, GSK1904529A, and silencing of DHCR24 was probed. The data are presented as the mean ± SD of three independent experiments. (*p < 0.05; **p < 0.01; ***p < 0.001).
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| S1088 |
NVP-ADW742NVP-ADW742是一种IGF-1R抑制剂，IC50为0.17 μM，作用于IGF-1R比作用于InsR效果强16倍以上；对HER2， PDGFR， VEGFR-2， Bcr-Abl和c-Kit几乎没有活性。 |
Relative cell viability of 72 hours of treatment with IGF1R/IR inhibitors. a-b OSI-906 does not inhibit chondrosarcoma cell viability, even in the presence of IGF1. c-d IGF1R inhibitors NVP-ADW742 and GSK1838705A do not inhibit chondrosarcoma cell viability
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| S1012 |
BMS-536924BMS-536924是一种ATP竞争性的IGF-1R抑制剂，IC50为100 nM，对Mek， Fak，和Lck也具有适中的抑制活性，但对Akt1，和MAPK1/2几乎无抑制活性。 |
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| S1234 |
AG-1024AG-1024 抑制IGF-1R自磷酸化，IC50为7 μM，对IR作用效果稍弱，IC50为57 μM，且特异性区分InsR和IGF-1R（相比于其他酪氨酸磷酸化抑制剂）。 |
(A) CLL B cells purified from freshly isolat ed or freeze-thawed PBMCs from CLL patient samples were treated with a single dose of 15 µM AG1024, 1µM PPP or 1µM linsitinib for 24h and cell survival was determined by flow cytometry. Results are shown as mean ± SEM, n=20. (B)CLL B cells purified from freshly isolat ed or freeze-thawed PBMCs from CLL patient samples were treated with a single dose of 15 µM AG1024 (AG) or 1µM linsitinib (L) and immunoblotted for the expression of phosphorylated IGF1R and IRS-1 (n=6). (C) CLL B cells purified from freshly isolat ed or freeze-thawed PBMCs from CLL patient samples were treated with a single dose of 1µM PPP and immunoblotted for the expression of phosphorylated IGF1R and IRS-1 (n=4). (D) CLL B cells purified from freshly isolated or freeze-thawed PBMCs from CLL patient samples were treated with 5-15 µM AG1024 and subject to a Western blot analysis using the indicated antibodies. Results are represented as mean±SEM (n=10). Supplementary Figure 1C shows the associated densitometrical analysis after treatment with 15 µM AG1024. (E) CLL B cells purified from freshly isolat ed or freeze-thawed PBMCs from CLL patient samples were treated with 10-500nM rhIGF-1 and immunoblotted for the expression of IGF1R, pIGF1R, pAkt, Akt, pERK and Erk. A representative example from four independent experiments is shown. |
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| S2703 |
GSK1838705AGSK1838705A是一种有效的IGF-1R抑制剂，IC50为2.0 nM，适度有效作用于IR和ALK，IC50分别为1.6 nM和0.5 nM，对其他蛋白激酶几乎没有作用活性。 |
Protective effect of IGF1 on Sorafenib or VK1-mediated actin cytoskeleton redistribution in HCC cells. PLC/PRF/5 and HLF cells were stained with DyLight 554 Phalloidin after treatment with 1 μM Sorafenib, 12 μM VK1 or 1 μM GSK1838705A (GSK) for 24 h alone or in combination with 40 ng/ml IGF1. Scale bar: 100 μm.
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| S1124 |
BMS-754807BMS-754807是一种有效的IGF-1R/InsR可逆性抑制剂，在无细胞试验中IC50为1.8 nM/1.7 nM，对Met，Aurora A/B，TrkA/B和Ron作用稍弱，对Flt3， Lck，MK2，PKA，PKC等几乎没有抑制活性。Phase 2。 |
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| S8003 |
PQ 401PQ 401抑制IGF-1R区域自磷酸化，IC50为低于1 μM。 |
IGF-1R is key determinant of the EI24-mediated gefitinib sensitivity. (A and B) EI24-knockdown cells were treated with the indicated concentrations of inhibitorsfor 24 h before cell viability was measured by the MTT assay. Error bars, S.D., p-values were calculated using unpaired t-test.*p < 0.01,**p = 0.0003,***p < 0.0001. (C and D)EI24-knockdown cells were fixed and stained with crystal violet after 14 days treatment with concentrations of gefitinib (0.1 M), PQ401 (5 M), and AG1024 (20 M). (Eand F) Kaplan–Meier survival plots were obtained using Kaplan–Meier Plotter and display the probability of overall survival of lung cancer patients grouped according toEI24 (208289 s at, E) and IGF-1R (203627 at, F) expression. p-Values were calculated using the log-rank test.
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| S7106 |
AZD3463AZD3463是一种新型的，口服有效的ALK抑制剂， Ki为0.75 nM，也等效抑制IGF1R 。 |
(E) Immunoblot analysis of lysates of A4573 and TC32 cells following exposure to media only (Control, C); ST/V and V/ST with (+) or without (-) 20 nM AZD3463 using antibodies against ALK, IGF-1R, STAT3 (Y705), p-STAT3, AKT, p-AKT (S473), MAPK, p-MAPK (p42/44). |
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| S8228 |
NT157NT157, 一种选择性IRS-1/2抑制剂，具有在癌细胞以及肿瘤微环境中的基质细胞中抑制IGF-1R和STAT3信号通路的潜力，因而减少癌细胞的生存率。 |
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| S7668 |
Picropodophyllin (PPP)Picropodophyllin (PPP)是一种选择性IGF-1R抑制剂，IC50为1 nM。它对IGF-IR具有高选择性，对IR的酪氨酸磷酸化或FGF-R、PDGF-R、EGF-R没有抑制作用。 |
CLL B cells purified from freshly isolated or freeze-thawed PBMCs from CLL patient samples were treated with a single dose of 1 µM PPP and were immunoblotted for the expression of phosphorylated IGF1R and IRS-1 (n = 4).
|
| 产品目录 | 产品描述 | 文献引用 | 实验数据 |
|---|---|---|---|
| S1091 |
Linsitinib (OSI-906)Linsitinib (OSI-906)是一种选择性IGF-1R抑制剂，在无细胞试验中IC50为35 nM；对InsR抑制作用适中，IC50为75 nM，对Abl，ALK，BTK，EGFR， FGFR1/2，PKA等没有抑制活性。Phase 3。 |
(e) c-peptide from these mice 240 min after respective treatments.
|
|
| S1034 |
NVP-AEW541NVP-AEW541是一种有效的IGF-1R/InsR抑制剂，在无细胞试验中IC50为150 nM/140 nM，在细胞试验中对IGF-1R具有较高的作用和选择性。 |
(A) KRAS mutant (SW837 and LoVo) or KRAS/PIK3CA mutant (HCT-116) colorectal cancers were treated with the indicated compounds for 6 hours (gef, gefitinib 1 μM; NVP, NVP-AEW541 1 μM; PHA, PHA-665752 1 μM), and the resulting protein lysates were immunoprecipitated with an anti-p85 antibody. The precipitated proteins were analyzed by Western blots with the indicated antibodies. Whole cell extracts were probed with the indicated antibodies. Asterisks indicate the IRS proteins for SW837 and HCT-116 cells, and ERBB3 for LoVo cells. (B) SW837 cells were grown in either normal serum (5% FBS) or low serum (0.5% FBS) and treated with vehicle, R1507 anti–IGF-IR antibody (25 μg/ml), or NVP-AEW541 (1 μM) for 6 hours. The cells were lysed and probed with the indicated antibodies. |
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| S1093 |
GSK1904529AGSK1904529A是一种选择性的IGF-1R和IR抑制剂，无细胞试验中IC50分别为27 nM和25 nM，作用于IGF-1R/InsR比作用于Akt1/2/， Aurora A/B，B-Raf， CDK2， EGFR等选择性高100倍以上。 |
(E) The level of migration ability of HEC-1B cells treated with insulin, GSK1904529A, and the silencing of DHCR24 was determined using a transwell assay. (F) The invasion ability of HEC-1B cells treated with insulin, GSK1904529A, and silencing of DHCR24 was probed. The data are presented as the mean ± SD of three independent experiments. (*p < 0.05; **p < 0.01; ***p < 0.001).
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| S1088 |
NVP-ADW742NVP-ADW742是一种IGF-1R抑制剂，IC50为0.17 μM，作用于IGF-1R比作用于InsR效果强16倍以上；对HER2， PDGFR， VEGFR-2， Bcr-Abl和c-Kit几乎没有活性。 |
Relative cell viability of 72 hours of treatment with IGF1R/IR inhibitors. a-b OSI-906 does not inhibit chondrosarcoma cell viability, even in the presence of IGF1. c-d IGF1R inhibitors NVP-ADW742 and GSK1838705A do not inhibit chondrosarcoma cell viability
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| S1012 |
BMS-536924BMS-536924是一种ATP竞争性的IGF-1R抑制剂，IC50为100 nM，对Mek， Fak，和Lck也具有适中的抑制活性，但对Akt1，和MAPK1/2几乎无抑制活性。 |
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|
| S1234 |
AG-1024AG-1024 抑制IGF-1R自磷酸化，IC50为7 μM，对IR作用效果稍弱，IC50为57 μM，且特异性区分InsR和IGF-1R（相比于其他酪氨酸磷酸化抑制剂）。 |
(A) CLL B cells purified from freshly isolat ed or freeze-thawed PBMCs from CLL patient samples were treated with a single dose of 15 µM AG1024, 1µM PPP or 1µM linsitinib for 24h and cell survival was determined by flow cytometry. Results are shown as mean ± SEM, n=20. (B)CLL B cells purified from freshly isolat ed or freeze-thawed PBMCs from CLL patient samples were treated with a single dose of 15 µM AG1024 (AG) or 1µM linsitinib (L) and immunoblotted for the expression of phosphorylated IGF1R and IRS-1 (n=6). (C) CLL B cells purified from freshly isolat ed or freeze-thawed PBMCs from CLL patient samples were treated with a single dose of 1µM PPP and immunoblotted for the expression of phosphorylated IGF1R and IRS-1 (n=4). (D) CLL B cells purified from freshly isolated or freeze-thawed PBMCs from CLL patient samples were treated with 5-15 µM AG1024 and subject to a Western blot analysis using the indicated antibodies. Results are represented as mean±SEM (n=10). Supplementary Figure 1C shows the associated densitometrical analysis after treatment with 15 µM AG1024. (E) CLL B cells purified from freshly isolat ed or freeze-thawed PBMCs from CLL patient samples were treated with 10-500nM rhIGF-1 and immunoblotted for the expression of IGF1R, pIGF1R, pAkt, Akt, pERK and Erk. A representative example from four independent experiments is shown. |
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| S2703 |
GSK1838705AGSK1838705A是一种有效的IGF-1R抑制剂，IC50为2.0 nM，适度有效作用于IR和ALK，IC50分别为1.6 nM和0.5 nM，对其他蛋白激酶几乎没有作用活性。 |
Protective effect of IGF1 on Sorafenib or VK1-mediated actin cytoskeleton redistribution in HCC cells. PLC/PRF/5 and HLF cells were stained with DyLight 554 Phalloidin after treatment with 1 μM Sorafenib, 12 μM VK1 or 1 μM GSK1838705A (GSK) for 24 h alone or in combination with 40 ng/ml IGF1. Scale bar: 100 μm.
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| S1124 |
BMS-754807BMS-754807是一种有效的IGF-1R/InsR可逆性抑制剂，在无细胞试验中IC50为1.8 nM/1.7 nM，对Met，Aurora A/B，TrkA/B和Ron作用稍弱，对Flt3， Lck，MK2，PKA，PKC等几乎没有抑制活性。Phase 2。 |
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| S8003 |
PQ 401PQ 401抑制IGF-1R区域自磷酸化，IC50为低于1 μM。 |
IGF-1R is key determinant of the EI24-mediated gefitinib sensitivity. (A and B) EI24-knockdown cells were treated with the indicated concentrations of inhibitorsfor 24 h before cell viability was measured by the MTT assay. Error bars, S.D., p-values were calculated using unpaired t-test.*p < 0.01,**p = 0.0003,***p < 0.0001. (C and D)EI24-knockdown cells were fixed and stained with crystal violet after 14 days treatment with concentrations of gefitinib (0.1 M), PQ401 (5 M), and AG1024 (20 M). (Eand F) Kaplan–Meier survival plots were obtained using Kaplan–Meier Plotter and display the probability of overall survival of lung cancer patients grouped according toEI24 (208289 s at, E) and IGF-1R (203627 at, F) expression. p-Values were calculated using the log-rank test.
|
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| S7106 |
AZD3463AZD3463是一种新型的，口服有效的ALK抑制剂， Ki为0.75 nM，也等效抑制IGF1R 。 |
(E) Immunoblot analysis of lysates of A4573 and TC32 cells following exposure to media only (Control, C); ST/V and V/ST with (+) or without (-) 20 nM AZD3463 using antibodies against ALK, IGF-1R, STAT3 (Y705), p-STAT3, AKT, p-AKT (S473), MAPK, p-MAPK (p42/44). |
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| S8228 |
NT157NT157, 一种选择性IRS-1/2抑制剂，具有在癌细胞以及肿瘤微环境中的基质细胞中抑制IGF-1R和STAT3信号通路的潜力，因而减少癌细胞的生存率。 |
||
| S7668 |
Picropodophyllin (PPP)Picropodophyllin (PPP)是一种选择性IGF-1R抑制剂，IC50为1 nM。它对IGF-IR具有高选择性，对IR的酪氨酸磷酸化或FGF-R、PDGF-R、EGF-R没有抑制作用。 |
CLL B cells purified from freshly isolated or freeze-thawed PBMCs from CLL patient samples were treated with a single dose of 1 µM PPP and were immunoblotted for the expression of phosphorylated IGF1R and IRS-1 (n = 4).
|
