PI3Kβ Inhibitor

IHMT-PI3K-455 (Compound 15u) is a potent, selective, orally active PI3Kγ/δ dual inhibitor with IC₅₀s of 7.1 nM and 0.57 nM for PI3Kγ and PI3Kδ, respectively. IHMT-PI3K-455 suppresses the AKT phosphorylation. IHMT-PI3K-455 inhibits tumor growth by recruiting and activating more CD8⁺ killing T cells.IHMT-PI3K-455 is used in cancer research.

PI3Kδ-IN-12 (compound 13) is a PI3Kδ inhibitor (pIC₅₀ = 5.8), with pKi values of 8.0/6.5/6.4/6.7 for PI3Kδ/γ/β/α, respectively. PI3Kδ-IN-12 can be used in the study of chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD).

PP162 is a selective DNA-dependent protein kinase (DNA-PK) inhibitor with an IC₅₀ of 53 nM. PP162 selectively inhibits DNA-PK by binding to a conserved hydrophobic pocket. PP162 exhibits weak inhibitory activity against various tyrosine kinases and PI3K family members. PP162 can be used for research on selective kinase targeting.

PI3Kδ-IN-21 (Compound 31) is a selective inhibitor for phosphoinositide 3-kinases δ (PI3Kδ), with an IC₅₀ of 13.6 nM. PI3Kδ-IN-21 inhibits proliferation and differentation of T cells through PI3K/AKT/mTOR signaling pathway. PI3Kδ-IN-21 exhibits good pharmacokinetic characters in rat model, and attenuates the experimental autoimmune encephalomyelitis in myelin oligodendrocyte glycoprotein (MOG)-induced EAE model.

ST-168 is an orally active MEK/PI3K inhibitor with an IC₅₀ of 182 nM against MEK1 and IC₅₀ values ​​of 69.2, 41.7, 1482 and 2293 nM against PI3Kα, PI3Kδ, PI3Kβ and PI3Kγ respectively. ST-168 completely inhibits the phosphorylation of ERK1/2 and AKT and induces cancer cell death in a 3D tumor sphere model. ST-168 demonstrates significant antitumor effects in the A375 melanoma mouse model. ST-168 improves the ocular toxicity profile of MEK inhibitors, showing lower caspase activation levels, indicating reduced apoptosis induction. ST-168 can be used in melanoma research.

PI3Kα-IN-14 (compound F8) is a selective PI3Kα inhibitor with an IC₅₀ of 0.14 nM. PI3Kα-IN-14 induces a great decrease in mitochondrial membrane which caused cell cycle arrest at G1 phase and apoptosis in U87-MG cells. PI3Kα-IN-14 shows significant anti-proliferative activities against three tumor-derived cell lines (PC-3: IC₅₀ of 0.28 μM; HCT-116: IC₅₀ of 0.57 μM; and U87-MG: IC₅₀ of 1.37 μM).

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.

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.

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.

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.

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.

LTURM 36 (20i) is a PI3K inhibitor, with IC₅₀ values ​​of 0.64 μM and 5.0 μM for PI3Kδ and PI3Kβ, respectively. LTURM 36 can be used in anticancer 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.

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.

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.

Izorlisib (CH5132799) methanesulfonate is an orally active, selective Class I PI3K inhibitor with an IC₅₀ value of 14 nM against PI3Kα. Izorlisib methanesulfonate specifically inhibits Class I PI3K (particularly PI3Kα and its mutants) and blocks the PI3K/Akt/mTOR pathway; this leads to cell cycle arrest at the G1 phase and apoptosis without triggering feedback activation of Akt by competitively binding to the ATP-binding site of PI3K. Izorlisib methanesulfonate can be used in research on cancers harboring PIK3CA mutations or PTEN loss (such as breast, ovarian, prostate, and endometrial cancers).

AM-0687 is a selective inhibitor for PI3Kδ with an IC₅₀ of 2.9 nM. AM-0687 decreases the levels of IgG and IgM specific antibodies, inhibits the anti-IgM/CD40L-induced proliferation of human B cell (IC₅₀=0.8 nM) and the phosphorylation of AKT (IC₅₀=0.7 nM), and exhibits anti-inflammatory efficacy.

PIK-C98 is a potent and selective PI3K inhibitor, with IC₅₀s of 0.59, 1.64, 3.65, and 0.74 μM for α, β, δ, and γ isoforms, respectively. PIK-C98 inhibits all class I PI3Ks but has no effects on AKT or mTOR activity. PIK-C98 interferes with the ATP-binding pockets of PI3Ks by forming H-bonds and arene-H interactions with specific amino acid residues. PIK-C98 induces apoptosis by inhibiting PI3K. PIK-C98 can be used for the research of multiple myeloma.

CAL-130 is a PI3Kδ and PI3Kγ inhibitor with IC₅₀s of 1.3 and 6.1 nM, respectively.