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Akt inhibitors target Akt, also called protein kinase B (PKB), a serine/threonine kinase in cell survival signaling. In 1995 the Akt proto-oncogene product was identified as a target of phosphatidylinositol 3-kinase (PI3K) activated by platelet-derived growth factor. Insulin and insulin-like growth factor 1 activate the kinase through phosphorylation at Thr308 and Ser473. The three isoforms, Akt1, Akt2 and Akt3, phosphorylate substrates that control metabolism, proliferation and apoptosis. The category includes the allosteric inhibitor MK-2206 2HCl, the catalytic-site inhibitor capivasertib and the alkylphospholipid perifosine. SC79, by contrast, promotes Akt phosphorylation and serves as an activator in pathway studies.
INY-03-041 is a potent and highly selective PROTAC-based pan-AKT degrader that targets AKT1, AKT2, and AKT3 with IC₅₀ values of 2.0 nM, 6.8 nM, and 3.5 nM, respectively. It is composed of the ATP-competitive AKT inhibitor GDC-0068 linked to the cereblon ligand lenalidomide, making it a valuable tool for studying AKT signaling and targeted cancer therapy.
MS15 TFA is a potent and selective PROTAC degrader targeting AKT isoforms. It inhibits the activity of AKT1, AKT2, and AKT3 with IC₅₀ values of 798 nM, 90 nM, and 544 nM, respectively. MS15 TFA serves as a valuable tool for studying AKT signaling and its role in cancer and metabolic diseases.
INY-05-040 is a potent and selective PROTAC degrader targeting all three isoforms of AKT (AKT1, AKT2, and AKT3). It induces rapid proteasomal degradation of AKT, effectively inhibiting downstream signaling pathways such as PI3K/AKT/mTOR, which are critical for cancer cell survival and proliferation. INY-05-040 demonstrates broad antiproliferative activity across 288 cancer cell lines, highlighting its potential as a powerful therapeutic agent for targeting AKT-driven malignancies.
MS21 is a potent AKT PROTAC degrader designed to selectively target and degrade AKT proteins. This compound effectively inhibits mutations within the PI3K/PTEN pathway, leading to suppressed tumor cell proliferation and induction of cell cycle arrest. MS21 demonstrates significant anti-tumor activity, making it a valuable tool for cancer research and therapeutic development.
MS170 is a highly selective PROTAC degrader targeting the AKT isoforms. With a DC50 value of 32 nM, MS170 effectively depletes total AKT (T-AKT) in cellular assays. It demonstrates strong binding affinity for AKT1, AKT2, and AKT3, with dissociation constants (Kd) of 1.3 nM, 77 nM, and 6.5 nM, respectively. This compound is suitable for research applications investigating AKT-related signaling pathways and therapeutic interventions in cancer biology.
MS5033 is a potent PROTAC-based degrader targeting AKT (protein kinase B). It demonstrates a DC50 value of 430 nM in PC3 cells, effectively promoting the degradation of AKT. This compound is valuable for studying AKT signaling pathways and evaluating the therapeutic potential of targeted protein degradation in cancer research.
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MS143 is a potent PROTAC degrader targeting AKT, demonstrating a DC50 of 46 nM and GI50 of 0.8 μM in PC3 cells. This compound effectively induces rapid and robust AKT degradation through the hijacking of the ubiquitin-proteasome system in a concentration- and time-dependent manner. MS143 holds promise in cancer research for its ability to suppress cell growth by promoting targeted protein degradation.
MS98 is a selective PROTAC degrader targeting AKT, effectively inducing the degradation of total AKT (T-AKT) with a DC50 value of 78 nM. This compound demonstrates high-affinity binding to AKT isoforms, with Kd values of 4 nM, 140 nM, and 8.1 nM for AKT1, AKT2, and AKT3, respectively. MS98 is valuable for research applications in understanding AKT signaling pathways and developing therapeutic strategies for cancer and other diseases associated with dysregulated AKT activity.
PROTAC Akt3 Degrader-1 is a selective PROTAC degrader that targets Akt3, facilitating the ubiquitin-proteasome mediated degradation of this protein. This compound demonstrates low antiproliferative activity across 36 different cell lines. PROTAC Akt3 Degrader-1 is applicable in research focused on Triple-negative breast cancer and melanoma, aiding in the understanding of Akt3’s role in these malignancies.
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MS15 is a selective AKT PROTAC degrader that demonstrates potent inhibition of AKT isoforms 1, 2, and 3, with IC50 values of 798 nM, 90 nM, and 544 nM, respectively. This compound facilitates the targeted degradation of AKT, making it a valuable tool for investigating AKT-related signaling pathways. Its applications include studying cellular processes like metabolism, growth, and survival in various cancer models.
Akt3 degrader 1 is a selective degrader that targets Akt3, effectively overcoming Osimertinib-induced resistance in H1975OR non-small cell lung cancer (NSCLC) cells. This compound demonstrates anti-proliferative effects and significantly inhibits tumor growth in murine models. Akt3 degrader 1 is a valuable tool for investigating mechanisms of drug resistance in NSCLC and can facilitate the development of novel therapeutic strategies.
