GSK1838705AIGF-IR/IR/ALK inhibitor, ATP-competitive CAS# 1116235-97-2 |
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Quality Control & MSDS
3D structure
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| Cas No. | 1116235-97-2 | SDF | Download SDF |
| PubChem ID | 25182616 | Appearance | Powder |
| Formula | C27H29FN8O3 | M.Wt | 532.57 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : ≥ 100 mg/mL (187.77 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | 2-[[2-[[1-[2-(dimethylamino)acetyl]-5-methoxy-2,3-dihydroindol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-6-fluoro-N-methylbenzamide | ||
| SMILES | CNC(=O)C1=C(C=CC=C1F)NC2=NC(=NC3=C2C=CN3)NC4=C(C=C5CCN(C5=C4)C(=O)CN(C)C)OC | ||
| Standard InChIKey | HZTYDQRUAWIZRE-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C27H29FN8O3/c1-29-26(38)23-17(28)6-5-7-18(23)31-25-16-8-10-30-24(16)33-27(34-25)32-19-13-20-15(12-21(19)39-4)9-11-36(20)22(37)14-35(2)3/h5-8,10,12-13H,9,11,14H2,1-4H3,(H,29,38)(H3,30,31,32,33,34) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | Potent insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF1R) inhibitor (IC50 values are 1.6 and 2 nM, respectively). Also inhibits anaplastic lymphoma kinase (ALK) (IC50 = 0.5 nM). Displays > 800-fold selectivity for IR, IGFR1 and ALK over a panel of 44 kinases including JNK. Blocks proliferation of cancer cell lines in vitro, and causes complete regression of ALK-dependent tumors in vivo. Orally bioavailable. |
GSK1838705A Dilution Calculator
GSK1838705A Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 1.8777 mL | 9.3884 mL | 18.7769 mL | 37.5537 mL | 46.9422 mL |
| 5 mM | 0.3755 mL | 1.8777 mL | 3.7554 mL | 7.5107 mL | 9.3884 mL |
| 10 mM | 0.1878 mL | 0.9388 mL | 1.8777 mL | 3.7554 mL | 4.6942 mL |
| 50 mM | 0.0376 mL | 0.1878 mL | 0.3755 mL | 0.7511 mL | 0.9388 mL |
| 100 mM | 0.0188 mL | 0.0939 mL | 0.1878 mL | 0.3755 mL | 0.4694 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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GSK1838705A is a small-molecule kinase inhibitor that inhibits IGF-IR and the insulin receptor with IC50s of 2.0 and 1.6 nmol/L, respectively.
IGF-1R is a transmembrane receptor which is activated by insulin-like growth factor 1 and by a related hormone IGF-2. This protein plays important role in the regulation of development. The insulin receptor is also a transmembrane receptor that is activated by insulin, IGF-1 and IGF2. This receptor is involved in insulin signaling pathway and plays an essential role in the regulation of glucose homeostasis.
GSK1838705A obstructs the in vitro expansion of cell lines got from strong and hematologic malignancies, including numerous myeloma and Ewing's sarcoma, and hinders the development of human tumor xenografts in vivo. In spite of the inhibitory impact of GSK1838705A on insulin receptor, insignificant effects on glucose homeostasis were seen at efficacious dosages. GSK1838705A represses the anaplastic lymphoma kinase (ALK), which drives the distorted development of anaplastic substantial cell lymphomas, some neuroblastomas, and a subset of non–small cell lung growths.
GSK1838705A restrains ALK, with an IC50 value of 0.5 nM, furthermore, causes complete relapse of ALK-ward tumors in vivo at very-endured measurements. GSK1838705A arrives for a promising antitumor agent for helpful use in human growth.
Reference:
[1]. Sabbatini P, et al. GSK1838705A inhibits the insulin-like growth factor-1 receptor and anaplastic lymphoma kinase and shows antitumor activity in experimental models of human cancers. Mol Cancer Ther. 2009 Oct;8(10):2811-20.
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GSK1838705A, an insulin-like growth factor-1 receptor/insulin receptor inhibitor, induces apoptosis and reduces viability of docetaxel-resistant prostate cancer cells both in vitro and in vivo.[Pubmed:25926740]
Onco Targets Ther. 2015 Apr 10;8:753-60.
Prostate cancer is the leading malignancy and the second most common cause of cancer-related death in men. Despite high cure rates with surgery and/or radiation, 30%-40% of patients eventually develop advanced cancer. Docetaxel is one of the most effective and well established chemotherapeutic agents for prostate cancer. However, docetaxel resistance often develops within months. Combination therapies have been proposed to improve the therapeutic efficacy of docetaxel in prostate cancer, and there is an urgent need to identify agents that are effective for treatment of the disease, especially docetaxel-resistant prostate cancer. In this work, we investigated the activity of GSK1838705A, a potent insulin-like growth factor-1 receptor (IGF1R)/insulin receptor (IR) inhibitor, in prostate cancer, especially docetaxel-resistant prostate cancer. We found that GSK1838705A could effectively reduce the viability of both docetaxel-sensitive and docetaxel-resistant prostate cancer cells. GSK1838705A induced marked apoptosis in docetaxel-resistant cells, and also dramatically inhibited migration of these cells. Further, GSK1838705A significantly inhibited phosphorylation of IGF1R/IR. Importantly, GSK1838705A significantly suppressed docetaxel-resistant PC-3R tumor growth in vivo. This is the first study of GSK1838705A in prostate cancer. Our results indicate that GSK1838705A is a promising compound for the treatment of prostate cancer, especially for those who develop resistance to docetaxel, and might shed new light on treatment for prostate cancer.
GSK1838705A, an IGF-1R inhibitor, inhibits glioma cell proliferation and suppresses tumor growth in vivo.[Pubmed:26238593]
Mol Med Rep. 2015 Oct;12(4):5641-6.
Glioma is a type of primary malignant tumor of the central nervous system in humans. At present, standard treatment involves surgical resection, followed by radiation therapy and chemotherapy. However, the prognosis is poor and the longterm survival rate remains low. An improved understanding of the molecular basis for glioma tumorigenesis is in urgently required. The prosurvival effect of the insulinlike growth factor (IGF) signaling pathway has been implicated in progression of the glioma disease state. GSK1838705A is a novel, small molecule kinase inhibitor of IGFIR, which inhibits IGF signal transduction and downstream target activation. Its anti-proliferative activity has been demonstrated in various tumor cell lines. The present study investigated the potential use of GSK1838705A for the treatment of glioma. Human U87MG glioma cells were used to examine the inhibitory activity of GSK1838705A in cell proliferation, migration and apoptosis. The antitumor activity of GSK1838705A was assessed in a xenograft mouse model. GSK1838705A inhibited the growth and induced the apoptosis of the U87MG glioma cells in a dosedependent manner. The GSK1838705Atreated cells exhibited reduced migratory activity in response to chemoattractants. The present study further demonstrated the antitumor activity of GSK1838705A in vivo. The administration of GSK1838705A significantly inhibited the growth of glioma tumors by inducing the apoptosis of tumor cells. These results suggested that targeting IGF signaling with GSK1838705A may be a promising therapeutic strategy for the treatment of patients with glioma.
GSK1838705A inhibits the insulin-like growth factor-1 receptor and anaplastic lymphoma kinase and shows antitumor activity in experimental models of human cancers.[Pubmed:19825801]
Mol Cancer Ther. 2009 Oct;8(10):2811-20.
The insulin-like growth factor-I receptor (IGF-IR) signaling pathway is activated in various tumors, and inhibition of IGF-IR kinase provides a therapeutic opportunity in these patients. GSK1838705A is a small-molecule kinase inhibitor that inhibits IGF-IR and the insulin receptor with IC(50)s of 2.0 and 1.6 nmol/L, respectively. GSK1838705A blocks the in vitro proliferation of cell lines derived from solid and hematologic malignancies, including multiple myeloma and Ewing's sarcoma, and retards the growth of human tumor xenografts in vivo. Despite the inhibitory effect of GSK1838705A on insulin receptor, minimal effects on glucose homeostasis were observed at efficacious doses. GSK1838705A also inhibits the anaplastic lymphoma kinase (ALK), which drives the aberrant growth of anaplastic large-cell lymphomas, some neuroblastomas, and a subset of non-small cell lung cancers. GSK1838705A inhibits ALK, with an IC(50) of 0.5 nmol/L, and causes complete regression of ALK-dependent tumors in vivo at well-tolerated doses. GSK1838705A is therefore a promising antitumor agent for therapeutic use in human cancers.
Site-specific activation of AKT protects cells from death induced by glucose deprivation.[Pubmed:23396361]
Oncogene. 2014 Feb 6;33(6):745-55.
The serine/threonine kinase AKT is a key mediator of cancer cell survival. We demonstrate that transient glucose deprivation modestly induces AKT phosphorylation at both Thr308 and Ser473. In contrast, prolonged glucose deprivation induces selective AKTThr308 phosphorylation and phosphorylation of a distinct subset of AKT downstream targets leading to cell survival under metabolic stress. Glucose-deprivation-induced AKTThr308 phosphorylation is dependent on PDK1 and PI3K but not EGF receptor or IGF1R. Prolonged glucose deprivation induces the formation of a complex of AKT, PDK1 and the GRP78 chaperone protein, directing phosphorylation of AKTThr308 but not AKTSer473. Our results reveal a novel mechanism of AKT activation under prolonged glucose deprivation that protects cells from metabolic stress. The selective activation of AKTThr308 phosphorylation that occurs during prolonged nutrient deprivation may provide an unexpected opportunity for the development and implementation of drugs targeting cell metabolism and aberrant AKT signaling.
Optimization of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine IGF-1R tyrosine kinase inhibitors towards JNK selectivity.[Pubmed:19071018]
Bioorg Med Chem Lett. 2009 Jan 15;19(2):360-4.
The SAR of C5' functional groups with terminal basic amines at the C6 aniline of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines is reported. Examples demonstrate potent inhibition of IGF-1R with 1000-fold selectivity over JNK1 and 3 in enzymatic assays.
