IGF-1R
信号通路图
研究领域
- 抑制剂选择性比较
- 溶解性比较
| 目录号 | 产品目录 | 溶解度(25°C) | ||
|---|---|---|---|---|
| 水 | DMSO | 酒精 | ||
| S1091 | Linsitinib (OSI-906) | <1 mg/mL | 84 mg/mL | <1 mg/mL |
| S1034 | NVP-AEW541 | <1 mg/mL | 88 mg/mL | <1 mg/mL |
| S1093 | GSK1904529A | <1 mg/mL | 124 mg/mL | <1 mg/mL |
| S1088 | NVP-ADW742 | <1 mg/mL | 10 mg/mL | 3 mg/mL |
| S1012 | BMS-536924 | <1 mg/mL | 96 mg/mL | <1 mg/mL |
| S1234 | AG-1024 | <1 mg/mL | 61 mg/mL | <1 mg/mL |
| S2703 | GSK1838705A | <1 mg/mL | 107 mg/mL | <1 mg/mL |
| S1124 | BMS-754807 | <1 mg/mL | 92 mg/mL | 92 mg/mL |
| S8003 | PQ 401 | <1 mg/mL | 32 mg/mL | <1 mg/mL |
| S7106 | AZD3463 | <1 mg/mL | 24 mg/mL | <1 mg/mL |
| S8228 | NT157 | <1 mg/mL | 82 mg/mL | 82 mg/mL |
| S7668 | Picropodophyllin (PPP) | <1 mg/mL | 82 mg/mL | 1 mg/mL |
- IGF-1R抑制剂（12）
| 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。 |
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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。 |
GSK1838705A suppresses glioma tumor growth and induces apoptosis in vivo. (A) Following inoculation of U87MG cells, formulated vehicle control or GSK1838705A (4 and 8 mg/kg) was injected into the corresponding group of nude mice (n=6/group) once daily. The tumors were measured every other day for 11 days and the tumor volumes were calculated. Starting on day 7, the differences between the treatment groups (4 and 8 mg/kg) and the vehicle control group were significant (P<0.05). (B) Body weights of the mice during the course of treatment were measured as an indication of significant cytotoxic effects. The data are expressed as the mean ± standard deviation. No significant differences are observed between any two of the groups during the course of treatment. (C) At the end of treatment, the tumors were harvested. GSK1838705A (8 mg/kg) induced the apoptosis of tumor cells in vivo, determined using a TUNEL assay (green) and nuclear staining with Hoechst (blue). Representative images are shown (magnification, ×40). TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling. |
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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。 |
PQ401 induces apoptosis in glioma cells. (A) U87MG cells were treated with PQ401 at the indicated concentrations for 48 hours, followed by PI staining and flow cytometry analysis. * indicates P < 0.05 by one-way ANOVA followed by Dunnet's test for comparisons between PQ401 treatments with various doses and no PQ401 treatment group. (B) U87MG cells were incubated with PQ401 for 48 hours. The nuclei were stained with Hoechst and analyzed using a fluorescent microscope. The representative images are presented. (C) The number of cells with condensed/fragmented nuclei was quantitated by counting in seven random fields and the inhibition was calculated. * indicates P < 0.05 by one-way ANOVA followed by Dunnet's test for comparisons between PQ401 treatments with various doses and no PQ401 treatment group.
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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。 |
(E): Expression levels of NANOG and p-IGF-IR were measured by immunoblotting in HCT116 and SW620 cells after treatment with IGF-II or PPP.
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