Name: GSK690693
Brand: GlpBio
SKU: GC13696
Availability: InStock
Rating: 5 (33 reviews)

GlpBio Products Cited In Reputable Papers

Nature
610.7931 (2022): 366-372

Nature
618, 1017–1023 (2023)

Cell
183.7 (2020): 1867-1883

Cell Research
31, 1291–1307 (2021)

Cell Research
33, 273–287 (2023)

Cell Research
33, 546–561 (2023)

Molecular Cancer
21.1 (2022): 1-17

Molecular Cancer
21.1 (2022): 1-18

Cancer Cell
39 (2021): 1-16

Cell Host Microbe
30.8 (2022): 1124-1138

Cell Host Microbe
31.5 (2023): 766-780

Cell Host Microbe
31.3 (2023): 418-43

Cell Metabolism
34.2 (2022): 240-255

Ann Rheum Dis
82(4): 533-545 (2023)

Cell Mol Immunol
20, 264–276 (2023)

Adv Funct Mater
33.35 (2023): 2214998

Product Documents

Quality Control & SDS

View current batch:

Purity: >99.00%

Protocol

Kinase experiment [1]:
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 experiment [2]:
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 experiment [3]:
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
References: [1]. Rhodes N, Heerding DA, et,al. Characterization of an Akt kinase inhibitor with potent pharmacodynamic and antitumor activity. Cancer Res. 2008 Apr 1;68(7):2366-74. doi: 10.1158/0008-5472.CAN-07-5783. PMID: 18381444.

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:
[1]. Rhodes N, Heerding DA, et,al. Characterization of an Akt kinase inhibitor with potent pharmacodynamic and antitumor activity. Cancer Res. 2008 Apr 1;68(7):2366-74. doi: 10.1158/0008-5472.CAN-07-5783. PMID: 18381444.
[2]. Levy DS, Kahana JA, et,al.AKT inhibitor, GSK690693, induces growth inhibition and apoptosis in acute lymphoblastic leukemia cell lines. Blood. 2009 Feb 19;113(8):1723-9. doi: 10.1182/blood-2008-02-137737. Epub 2008 Dec 8. PMID: 19064730.
[3]. Altomare DA, Zhang L, et,al.GSK690693 delays tumor onset and progression in genetically defined mouse models expressing activated Akt. Clin Cancer Res. 2010 Jan 15;16(2):486-96. doi: 10.1158/1078-0432.CCR-09-1026. PMID: 20075391; PMCID: PMC2807995.
[4]. Crouthamel MC, Kahana JA, et,al.Mechanism and management of AKT inhibitor-induced hyperglycemia. Clin Cancer Res. 2009 Jan 1;15(1):217-25. doi: 10.1158/1078-0432.CCR-08-1253. PMID: 19118049.
[5]. Sun L, Cui K, et,al.Akt dependent adult hippocampal neurogenesis regulates the behavioral improvement of treadmill running to mice model of post-traumatic stress disorder. Behav Brain Res. 2020 Feb 3;379:112375. doi: 10.1016/j.bbr.2019.112375. Epub 2019 Nov 20. PMID: 31759046.
[6]. Cheng X, Xie M, et,al.Inhibitor GSK690693 extends Drosophila lifespan via reduce AKT signaling pathway. Mech Ageing Dev. 2022 Mar;202:111633. doi: 10.1016/j.mad.2022.111633. Epub 2022 Jan 20. PMID: 35065134.
[7]. Pradeepa, Suresh V, et,al.AKT inhibition sensitizes EVI1 expressing colon cancer cells to irinotecan therapy by regulating the Akt/mTOR axis. Cell Oncol (Dordr). 2022 Aug;45(4):659-675. doi: 10.1007/s13402-022-00690-9. Epub 2022 Jul 14. PMID: 35834097.

Cas No.	937174-76-0	SDF
Chemical Name	4-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-[[(3S)-piperidin-3-yl]methoxy]imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol
Canonical SMILES	CCN1C2=C(C(=NC=C2OCC3CCCNC3)C#CC(C)(C)O)N=C1C4=NON=C4N
Formula	C₂₁H₂₇N₇O₃	M.Wt	425.48
Solubility	≥ 21.25mg/mL in DMSO	Storage	Store at -20°C
General tips	Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition	Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

Prepare stock solution
		1 mg	5 mg	10 mg
	1 mM	2.3503 mL	11.7514 mL	23.5029 mL
	5 mM	0.4701 mL	2.3503 mL	4.7006 mL
	10 mM	0.235 mL	1.1751 mL	2.3503 mL

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

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3. All of the above co-solvents are available for purchase on the GlpBio website.

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