Akt3 Inhibitor

MK-2206 dihydrochloride (MK-2206 2HCl) 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 dihydrochloride inhibits the Akt/mTOR signaling pathway and reduces the levels of downstream GSK3β and Mcl-1 via proteasomal degradation. MK-2206 dihydrochloride induces G1-phase cell cycle arrest, apoptosis, epithelial-mesenchymal transition, fibroblast activation and extracellular matrix deposition. MK-2206 dihydrochloride causes transient hyperglycemia and hyperinsulinemia in animals. MK-2206 dihydrochloride can be used in research related to solid tumors, renal fibrosis and hypercholesterolemia.

Capivasertib (AZD5363) is an orally active and potent pan-AKT kinase inhibitor with IC₅₀ of 3, 7 and 7 nM for Akt1,Akt2 and Akt3, respectively.

Ipatasertib (GDC-0068) 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 synchronously activates FoxO3a and NF-κB through inhibition of Akt leading to p53-independent activation of PUMA. Ipatasertib also induces apoptosis in cancer cells and inhibits tumor growth in xenograft mouse models.

AKT inhibitor VIII (AKTi-1/2) is a cell-permeable quinoxaline compound that has been shown to potently, selectively, allosterically, and reversibly inhibit Akt1, Akt2, and Akt3 activity with IC₅₀s of 58 nM, 210 nM, and 2119 nM, respectively.

Miransertib (ARQ-092) 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 is also a potent the AKT1-E17K mutant protein inhibitor and has the potential for PI3K/AKT-driven tumors and Proteus syndrome research. Miransertib is effective against Leishmania.

MK-2206 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 inhibits the Akt/mTOR signaling pathway and reduces the levels of downstream GSK3β and Mcl-1 via proteasomal degradation. MK-2206 induces G1-phase cell cycle arrest, apoptosis, epithelial-mesenchymal transition, fibroblast activation and extracellular matrix deposition. MK-2206 causes transient hyperglycemia and hyperinsulinemia in animals. MK-2206 can be used in research related to solid tumors, renal fibrosis and hypercholesterolemia.

GSK-690693 is an ATP-competitive pan-Akt inhibitor with IC₅₀s of 2 nM, 13 nM, 9 nM for Akt1, Akt2 and Akt3, respectively. GSK-690693 is also an AMPK inhibitor, affects Unc-51-like autophagy activating kinase 1 (ULK1) activity and robustly inhibits STING-dependent IRF3 activation.

Afuresertib (GSK2110183) is an orally bioavailable, selective, ATP-competitive and potent pan-Akt kinase inhibitor with K_is of 0.08/2/2.6 nM for Akt1/Akt2/Akt3, respectively.

Uprosertib (GSK2141795) is a potent and selective pan-Akt inhibitor with IC₅₀ values of 180/328/38 nM for Akt1/Akt2/Akt3, respectively.

Ipatasertib dihydrochloride (GDC-0068 dihydrochloride) is a highly selective and ATP-competitive pan-Akt inhibitor with IC₅₀s of 5, 18 and 8 nM for Akt1, Akt2 and Akt3, respectively.

A-443654 is a pan-Akt inhibitor and has equal potency against Akt1, Akt2, or Akt3 within cells (K_i=160 pM).

BAY1125976, a chemical probe, is a selective allosteric Akt1/Akt2 inhibitor; inhibits Akt1 and Akt2 activity with IC₅₀ values of 5.2 nM and 18 nM at 10 μM ATP, respectively.

INY-03-041 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, Cereblon ligand). INY-03-041 inhibits AKT1, AKT2 and AKT3 with IC₅₀s of 2.0, 6.8 and 3.5 nM, respectively.

Engasertib is an orally active highly specific AKT inhibitor with IC₅₀ values of 0.13 µM, 0.09 µM and 2.75 µM for AKT1, AKT2 and AKT3, respectively. Engasertib inhibits AKT phosphorylation and modulates downstream signalling in vitro. Engasertib can inhibit cancer cell proliferation and tumor growth.

AT7867 is a potent ATP-competitive inhibitor of Akt1/Akt2/Akt3 and p70S6K/PKA with IC₅₀s of 32 nM/17 nM/47 nM and 85 nM/20 nM, respectively.

AT13148 is an orally active and ATP-competitive, multi-AGC kinase inhibitor with IC₅₀s of 38 nM/402 nM/50 nM, 8 nM, 3 nM, and 6 nM/4 nM for Akt1/2/3, p70S6K, PKA, and ROCKI/II, respectively.

Pifusertib (TAS-117) hydrochloride 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 hydrochloride triggers anti-myeloma activities and enhances fatal endoplasmic reticulum (ER) stress induced by proteasome inhibition. Pifusertib hydrochloride induces apoptosis and autophagy.

Vevorisertib (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.

M2698 (MSC2363318A) is an orally active, ATP competitive, selective p70S6K and Akt dual-inhibitor with IC₅₀s of 1 nM for p70S6K, Akt1 and Akt3. M2698 can cross the blood-brain barrier and has anti-cancer activity.

AKT-IN-6 (Example 13) is a potent Akt inhibitor. AKT-IN-6 inhibits Akt1, Akt2 and Akt3 with IC₅₀s < 500nM, respectively. (patent WO2013056015A1).