| 包装 | 价格(元) |
| 10mM (in 1mL DMSO) | 电议 |
| 5mg | 电议 |
| 10mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
Preparation Method | To more accurately measure time-dependent inhibition of Akt, activated Akt enzymes were incubated with GSK690693 at various concentrations at room temperature for 30 min before the reaction was initiated with the addition of substrate. Final reaction contains 5 to 15 nmol/L Akt1, 2, and 3 enzymes; 2 μmol/L ATP; 0.15 μCi/μL [γ 33P]ATP; 1 μmol/L Peptide; 10 mmol/L MgCl2; 25 mmol/L MOPS (pH 7.5); 1 mmol/L DTT; 1 mmol/L CHAPS; and 50 mmol/L KCl. The reactions were incubated at room temperature for 45 min, followed by termination with Leadseeker beads in PBS containing EDTA. |
Applications | GSK690693 is an ATP-competitive, low nanomolar inhibitor of Akt kinases with IC50 values of 2, 13, and 9 nM for Akt1, 2, and 3, respectively. The apparent Ki*s for full-length Akt1, 2, and 3 were determined as 1, 4, and 12 nM, respectively. |
Cell lines | BT474 cells |
Preparation Method | For Western blot analysis of various substrates of Akt phosphorylation, BT474 cells were treated with GSK690693 at concentrations ranging from 10 μmol/L to 1 nmol/L. |
Reaction Conditions | 10 μM to 1 nM GSK690693 for 5 hours |
Applications | The phosphorylation of FKHR/FKHRL1, p70S6K, GSK3α/β, and PRAS40 in BT474 breast tumor cells was inhibited by GSK690693 in a dose-dependent manner. |
Animal models | 8- to 12-wk-old CD1 Swiss Nude mice |
Preparation Method | Tumors were initiated by injection of tumor cell suspension or tumor fragments s.c. in 8- to 12-wk-old CD1 Swiss Nude mice or SCID mice. When tumors reached a volume, mice were randomized and divided into groups of 8 to 12 mice per group. GSK690693 was administered once daily at 10, 20, and 30 mg/kg by i.p. administration. |
Dosage form | GSK690693 was administered once daily at 10, 20, and 30 mg/kg by i.p. administration. |
Applications | Repeated i.p. administration (once daily for 21 days) produced significant antitumor activity in mice bearing established SKOV-3 ovarian, LNCaP prostate, and BT474 and HCC-1954 breast carcinoma xenografts. Maximal inhibition of 58% to 75% was observed at the end of dosing period with 30 mg/kg/day dose. Daily administration of GSK690693 for 21 days was well-tolerated in mice with |
| 产品描述 | GSK690693 is an ATP-competitive, low nanomolar inhibitor of Akt kinases with IC50 values of 2, 13, and 9 nM for Akt1, 2, and 3, respectively. The apparent Ki for full-length Akt1, 2, and 3 were determined as 1, 4, and 12 nM, respectively. GSK690693 inhibited the phosphorylation of FKHR/FKHRL1, p70S6K, GSK3α/β, and PRAS40 in BT474 breast tumor cells in a dose-dependent manner[1]. The antiproliferative effect was selective for the malignant cells, as GSK690693 did not inhibit the proliferation of normal human CD4(+) peripheral T lymphocytes as well as mouse thymocytes. Phosphorylation of downstream substrates of AKT was reduced in both sensitive and insensitive cell lines on treatment with GSK690693[2]. GSK690693 was most effective in delaying tumor progression in Lck-MyrAkt2 mice expressing a membrane-bound, constitutively active form of Akt. Both tumors and primary cell cultures displayed downregulation of the Akt pathway, increased apoptosis, and primarily decreased cell proliferation[3].Repeated i.p. administration (once daily for 21 days) produced significant antitumor activity in mice bearing established SKOV-3 ovarian, LNCaP prostate, and BT474 and HCC-1954 breast carcinoma xenografts. Maximal inhibition of 58% to 75% was observed at the end of dosing period with 30 mg/kg/day dose. Daily administration of GSK690693 for 21 days was well-tolerated in mice with [1]. Treatment with antidiabetic agents does not significantly affect GSK690693-induced hyperglycemia in rodents. However, administration of GSK690693 in mice significantly reduces liver glycogen (approximately 90%), suggesting that GSK690693 may inhibit glycogen synthesis and/or activate glycogenolysis[3]. Interrupting treadmill running administrated mice with Akt inhibitor GSK690693 resulted in the blocked the effects of treadmill running to hippocampal neurogenesis and behavioral improvement in PTSD mice model[5]. AKT inhibitor GSK690693 can extend lifespan in Drosophila irrespective of start of the treatment from the beginning of life or the mid-life. Effect of GSK690693 for lifespan extension has been primarily related to the improvements in oxidative resistance, intestinal integrity and increased autophagy, but not in physical activity or starvation resistance[6]. EVI1 knockdown decreased cancer stem cell-like properties and improved irinotecan responses in both cell line and subcutaneous mouse models. Co-treatment with irinotecan and GSK690693 significantly reduced colon cancer cell survival and tumor progression rates[7]. References: |
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