Akt3
AKT serine/threonine kinase 3 (AKT3) is a PI3K-AKT pathway effector that regulates cellular growth, survival, and neurodevelopment, with particularly high expression in the central nervous system[1][2]. Mechanistically, AKT3 contributes to mTOR signaling and postnatal brain growth by controlling both cell size and cell number, and Akt3-deficient mice display selective reductions in brain volume without major disturbances in glucose homeostasis[1][3]. In disease models, somatic activating mutations and copy-number alterations of AKT3 are associated with megalencephaly-spectrum neurodevelopmental disorders and hemispheric brain overgrowth, supporting a central role for AKT3 during cortical development and neural progenitor regulation[4]. Compared with related isoforms, AKT1 primarily regulates organismal growth, whereas AKT2 is closely linked to insulin-responsive metabolic tissues; in contrast, AKT3 shows brain-enriched expression and mediates isoform-specific control of neural growth and signaling outputs[1][2][3]. Beyond developmental biology, genomically amplified AKT3 promotes glioma progression and activates DNA repair programs, identifying AKT3 as a functionally dominant AKT isoform in specific brain tumor contexts[5]. For experimental applications, recent medicinal chemistry efforts have produced isoform-selective AKT3 degraders that induce proteasomal degradation of AKT3 and suppress growth of resistant cancer models, providing tools for dissecting AKT3-specific signaling and therapeutic vulnerabilities[6].
References:
- [1]. Easton RM, et al. Role for Akt3/protein kinase Bgamma in attainment of normal brain size. Mol Cell Biol. 2005 Mar;25(5):1869-78. [Content Brief]
- [2]. Khalili M, et al. Underserved Does Not Mean Undeserved: Unfurling the HCV Care in the Safety Net. Dig Dis Sci. 2018 Dec;63(12):3250-3252. [Content Brief]
- [3]. Tschopp O, et al. Essential role of protein kinase B gamma (PKB gamma/Akt3) in postnatal brain development but not in glucose homeostasis. Development. 2005 Jul;132(13):2943-54. [Content Brief]
- [4]. Poduri A, et al. Somatic activation of AKT3 causes hemispheric developmental brain malformations. Neuron. 2012 Apr 12;74(1):41-8. [Content Brief]
- [5]. Turner KM, et al. Genomically amplified Akt3 activates DNA repair pathway and promotes glioma progression. Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):3421-6. [Content Brief]
- [6]. Xu F, et al. Discovery of Isoform-Selective Akt3 Degraders Overcoming Osimertinib-Induced Resistance in Non-Small Cell Lung Cancer Cells. J Med Chem. 2022 Oct 27;65(20):14032-14048. [Content Brief]
-
Akt3 Related Products (43)
Related Products (43)
-
Recombinant Proteins (6)
-
Vevorisertib trihydrochloride
0 ImagesSynonyms: ARQ 751 trihydrochlorideVevorisertib (ARQ 751) trihydrochloride is a selective, allosteric, pan-AKT and AKT1-E17K mutant inhibitors. Vevorisertib trihydrochloride potently inhibit phosphorylation of AKT. Vevorisertib trihydrochloride has Kd values of 1.2 nM and 8.6 nM for AKT1 and AKT1-E17K, respectively. Vevorisertib trihydrochloride has IC50 values of 0.55, 0.81, and 1.3 nM for AKT1, AKT2, and AKT3, respectively. Vevorisertib trihydrochloride can be used for the research of cancer.
-
AKT-IN-6
0 ImagesAKT-IN-6 (Example 13) is a potent Akt inhibitor. AKT-IN-6 inhibits Akt1, Akt2 and Akt3 with IC50s < 500nM, respectively. (patent WO2013056015A1).
-
Miransertib hydrochloride
0 ImagesSynonyms: ARQ-092 hydrochlorideMiransertib hydrochloride (ARQ-092 hydrochloride) is a potent, orally active, selective and allosteric Akt inhibitor with IC50s of 2.7 nM, 14 nM and 8.1 nM for Akt1, Akt2, Akt3, respectively. Miransertib hydrochloride is also a potent the AKT1-E17K mutant protein inhibitor and has the potential for PI3K/AKT-driven tumors and Proteus syndrome research. Miransertib hydrochloride is effective against Leishmania.
-
Vevorisertib
0 ImagesSynonyms: ARQ 751Vevorisertib (ARQ 751) is an orally active, potent and selective pan-AKT serine/threonine kinase inhibitor against AKT1 (IC50=0.55 nM), AKT2 (IC50=0.81 nM), and AKT3 (IC50=1.31 nM). Vevorisertib, as a single agent or in combination with other anti-cancer agents, can be used for the research of solid tumors with PIK3CA / AKT / PTEN mutations.
-
INY-03-041 trihydrochloride
0 ImagesCat. No.: HY-133120AINY-03-041 trihydrochloride is a potent, highly selective and PROTAC-based pan-AKT degrader consisting of the ATP-competitive AKT inhibitor Ipatasertib (HY-15186) conjugated to Lenalidomide (HY-A0003). INY-03-041 trihydrochloride inhibits AKT1, AKT2 and AKT3 with IC50s of 2.0, 6.8 and 3.5 nM, respectively.
-
Pifusertib
0 ImagesSynonyms: TAS-117Pifusertib (TAS-117) is a potent, selective, orally active allosteric Akt inhibitor (with IC50s of 4.8, 1.6, and 44 nM for Akt1, 2, and 3, respectively). Pifusertib triggers anti-myeloma activities and enhances fatal endoplasmic reticulum (ER) stress induced by proteasome inhibition. Pifusertib induces apoptosis and autophagy.
-
AKT-IN-3
0 ImagesAKT-IN-3 (compound E22) is a potent, orally active low hERG blocking Akt inhibitor, with 1.4 nM, 1.2 nM and 1.7 nM for Akt1, Akt2 and Akt3, respectively. AKT-IN-3 (compound E22) also exhibits good inhibitory activity against other AGC family kinases, such as PKA, PKC, ROCK1, RSK1, P70S6K, and SGK. AKT-IN-3 (compound E22) induces apoptosis and inhibits metastasis of cancer cells.
-
MS143
0 ImagesCat. No.: HY-143883CAS No.: 2376137-41-4MS143 is a VHL-recruiting AKT protein PROTAC degrader with a DC50 of 46 nM in PC3 prostate cancer cells. MS143 preferentially binds to AKT1 and AKT3, with weaker binding activity towards AKT2. MS143 degrades AKT and blocks the phosphorylation of downstream signaling molecules in the PI3K/AKT/mTOR pathway. MS143 inhibits cancer cell growth and xenograft tumor growth. MS143 can be used for research on prostate cancer, triple-negative breast cancer, and breast cancer.
-
Hu7691 free base
0 ImagesCat. No.: HY-132302ACAS No.: 2241232-43-7
-
MS98
0 ImagesCat. No.: HY-145281CAS No.: 2376137-31-2MS98 is a AKT PROTAC degrader with a DC50 of 78 nM in BT474 cells. MS98 binds to purified AKT1, AKT2 and AKT3 isoforms with Kd values of 4 nM, 140 nM and 8 nM, respectively. MS98 recruits the VHL E3 ligase to induce polyubiquitination and proteasomal degradation of AKT. MS98 inhibits downstream signal transduction of the PI3K/AKT/m-TOR pathway. MS98 suppresses cancer cell proliferation. MS98 can be used for the research of prostate cancer and breast cancer.
-
MK-2206 free base
0 ImagesCat. No.: HY-10357CAS No.: 1032349-93-1MK-2206 free base is an orally active pan-AKT inhibitor, with IC50 values of 8 nM, 12 nM and 65 nM against AKT1, AKT2 and AKT3, respectively. MK-2206 free base inhibits the Akt/mTOR signaling pathway and reduces the levels of downstream GSK3β and Mcl-1 via proteasomal degradation. MK-2206 free base induces G1-phase cell cycle arrest, apoptosis, epithelial-mesenchymal transition, fibroblast activation and extracellular matrix deposition. MK-2206 free base causes transient hyperglycemia and hyperinsulinemia in animals. MK-2206 free base can be used in research related to solid tumors, renal fibrosis and hypercholesterolemia.
-
PROTAC Akt3 Degrader-1
0 ImagesCat. No.: HY-175975CAS No.: 3048204-93-6
-
Ipatasertib tosylate
0 ImagesCat. No.: HY-15186CCAS No.: 1491138-24-9Synonyms: GDC-0068 tosylate; RG7440 tosylateIpatasertib (GDC-0068) tosylate is an orally active, highly selective and ATP-competitive pan-Akt inhibitor with IC50 values of 5, 18, 8 nM for Akt1/2/3, respectively. Ipatasertib tosylate synchronously activates FoxO3a and NF-κB through inhibition of Akt leading to p53-independent activation of PUMA. Ipatasertib tosylate also induces apoptosis in cancer cells and inhibits tumor growth in xenograft mouse models.
