PI3Kα Inhibitor

PI3K-IN-4 is a potent Pan-PI3K inhibitor. PI3K-IN-4 has high activity for three PI3K isoforms with the IC₅₀ values of picomole. PI3K-IN-4 shows superior inhibitory activity against PI3Kα (IC₅₀ = 0.20 nM), PI3Kβ (IC₅₀ = 2.99 nM), PI3Kδ (IC₅₀ = 0.48 nM) and PI3Kγ (IC₅₀ = 0.58 nM) and has no significant activity against EGFR. PI3K-IN-4 inhibits cancer cell growth though PI3K/Akt signaling pathway, leading to the inhibition of colony formation and the induction of apoptosis. PI3K-IN-4 can be used for lung, colon and breast cancer research.

PI3Kα-IN-23 (Compound 9) is an inhibitor of PI3Ka H1047R.

PI3K/HDAC-IN-4 (Compound 31f) is a PI3K/HDAC dual inhibitor (IC₅₀: 0.2μM). PI3K/HDAC-IN-4 shows high selectivity for HDAC1-3 (IC₅₀ values of 75.5 nM, 70.9 nM, and 1.9 nM, respectively). PI3K/HDAC-IN-4 is a potent PIK3 inhibitor with IC₅₀ values of 2.5 nM, 80.5 nM, 10.0 nM, and 57.2 nM for PI3Kα, β, δ, and γ, respectively. PI3K/HDAC-IN-4 significantly induces tumor cell apoptosis by simultaneously inhibiting the PI3K/AKT/mTOR signaling pathway and HDAC1-3. PI3K/HDAC-IN-4 exhibits potent antiproliferative activity in a variety of tumor cell lines (e.g., MV4-11, Jeko-1, HL60, and MCF-7, with IC₅₀ values of 0.2, 0.9, 0.8, and 1.5 μM, respectively). PI3K/HDAC-IN-4 can be used in the study of lymphoma and leukemia.

CC-11 is an orally active small molecule drug conjugate (SMDC) that links the PI3K/mTOR inhibitor with the extracellular heat shock protein 90 (EHSP90) targeting ligand through a cleavable linker. CC-11 exhibits strong HSP90 binding activity (IC₅₀ = 15 nM) and inhibits PI3Kα kinase activity (IC₅₀ = 0.54 nM). CC-11 has anti-proliferative activity against colon cancer cells. CC-11 shows significant efficacy in the HCT-116 xenograft tumor model. CC-11 can be used for research on colon cancer.

SJY26 is a PI3K/HDAC dual-target inhibitor with IC₅₀s of 0.59 nM (PI3Kα and PI3Kδ), 2.02 nM (PI3Kγ), 12.69 nM (PI3Kβ) and 114 nM (HDAC1). SJY26 exhibits potent broad-spectrum anti-proliferative activity, and is particularly sensitive to Jurkat and PC9R cells. SJY26 inhibited the migration of PC9R cells, arrested the cell cycle and induced cell apoptosis. SJY26 reduces AKT phosphorylation, and decreases histone H3 deacetylation (Ac-H3). SJY26 can be used for the studies of non-small cell lung cancer and leukemia.

SRX3212 is a potent PI3Kα/BRD4 inhibitor with human IC₅₀ values of 22 nM, 3.7 nM, and 32 nM for PI3Kα, BRD4_BD1, and BRD4_BD2, respectively. SRX3212 inhibits PI3K kinase activity and blocks acetyllysine binding function of BRD4_BD1 and BRD4_BD2. SRX3212 can be used for the research of mantle cell lymphoma, colon carcinoma, neuroblastoma, prostate cancer^[1].

PI3K/mTOR-IN-24 (compound 5nh) is a potent inhibitor of PI3K/mTOR, with the inhibitor of 0.45 and 2.9 nM for PI3Kα and mTOR, respectively. PI3K/mTOR-IN-24 plays an important role in cancer research.

VVD-844 is an orally active covalent inhibitor of PI3Kα, which inhibits Pl3Kα/p110α interaction with an IC₅₀ of 4 nM. VVD-844 covalently binds to Cys²⁴² in the RAS binding domain of p110α, blocking RAS-p110α interaction and inhibiting PI3Kα activity. VVD-844 inhibits PI3Kα signaling activation in HER2-overexpressing cells via a RAS-independent mechanism. VVD-844 suppresses tumor growth in mouse. VVD-844 can be used for the research of cancers.

PI3Kα-IN-8 (Compound 9g) is a selective PI3Kα inhibitor with an IC₅₀ of 0.012 μM. PI3Kα-IN-8 increases intracellular reactive oxygen species level, decreases mitochondrial membrane potential and induces apoptosis.

PI3Kα-IN-1 is a PI3Kα inhibitor (IC₅₀ < 0.5 nM), and also inhibits mTOR (IC₅₀: 104 nM).

PI3Kδ-IN-26 (Compound 58) is a selective and orally active PI3Kδ inhibitor with an IC₅₀ of 14  nM. PI3Kδ-IN-26 significantly attenuates the inflammatory responses in house dust mite (HDM) induced chronic asthma mouse models. PI3Kδ-IN-26 can be used for inflammatory, autoimmune and hyperproliferative diseases research.

CC-M-1 is a potent and selective PI3K/mTOR inhibitor. CC-M-1 inhibits PI3Kα/β/γ/δ and mTOR with IC₅₀ values of 0.68, 1.02, 1.03, 8.03, and 15 nM, respectively. CC-M-1 inhibits the proliferation of colorectal cancer cell lines, including HCT-116 (IC₅₀ = 0.38 μM) and HT-29 (IC₅₀ = 1.70 μM). CC-M-1 can be used for colorectal cancer (CRC) research.

mTOR inhibitor-13 (compound 9g), an aryl ureido compound, is a potent and selective mTOR inhibitor with an IC₅₀ of 0.29 nM. mTOR inhibitor-13 also inhibits PI3K-α with an IC₅₀ of 119 nM.

PI3Kα-IN-24 (WR23) is a PI3Kα inhibitor with an IC₅₀ of 0.025 μM and exhibits a significant pAkt^Ser473 suppression effect. PI3Kα-IN-24 can be utilized in cancer research.

mTOR inhibitor-17 (Compound 9e) is a selective inhibitor for mTOR. mTOR inhibitor-10 inhibits mTOR and PI3K-α, with IC₅₀ of 0.68 and 1359 nM. mTOR inhibitor-10 inhibits proliferation of LNCaP with IC₅₀ of 40 nM.

RV-6153 is a potent and selective dual inhibitor of PI3Kδ and PI3Kγ, with IC₅₀ values of 2.5 nM and 28 nM, respectively. RV-6153 dually inhibits PI3Kδ and PI3Kγ, blocking Akt phosphorylation, thereby inhibiting ROS production and cytokine release at the cellular level, and reducing neutrophil and macrophage accumulation in the airways in vivo. RV-6153 can be used in research on chronic obstructive pulmonary disease, asthma, and other inflammatory diseases.

PI4K-IN-3 (Compound 27) is an orally active PI4K inhibitor with an IC₅₀ of 1.9  nM for Plasmodium vivax PI4K. PI4K-IN-3 has no hERG channel inhibition and mammalian cytotoxicity. PI4K-IN-3 has significant selectivity against the human MINK1 and MAP4K4 kinases but with low selectivity against human PI3Kα and PI4Kβ. PI4K-IN-3 has potent antimalarial activity and significantly reduces parasitaemia in NSG mice mouse models of Plasmodium falciparum malaria.

PI3K-IN-54 (compound 10w) is a pan-PI3K inhibitor. The IC₅₀ values of PI3K-IN-54 for p110α, p110β, and p110δ are 0.22 nM, 1.4 nM, and 0.38 nM, respectively. PI3K-IN-54 can be used in cancer research.

PI3Kγ inhibitor 1 is a PI3Kδ and PI3Kγ inhibitor extracted from patent WO2014004470A1, Compound 168 in Table 4, has IC₅₀s of <100 nM.

mTOR inhibitor-16 (Compound 9f) is a selective inhibitor for mTOR. mTOR inhibitor-10 inhibits mTOR and PI3K-α, with IC₅₀ of 1.25 and 82 nM. mTOR inhibitor-10 inhibits proliferation of LNCaP with IC₅₀ of 140 nM.