PI3Kα Inhibitor

HM5023507 is an orally active and selective PI3Kδ/γ inhibitor with IC₅₀s of 4  and 5  μM for PI3Kδ and PI3Kγ over PI3Kβ and PI3Kα. HM5023507 attenuates the PI3Kδ/γ signaling in human basophils. HM5023507 also attenuates the activation and function of human B and T cells and cytokine and IgG production during cocultures, and Th17 differentiation of CD4 T cells. HM5023507 inhibited semiestablished collagen-induced arthritic inflammation in the rat models. HM5023507 can be used for inflammatory diseases like rheumatoid arthritis research.

PI3Kα-IN-11 is a potent PI3Kα inhibitor with anticancer activity.

PI3Kγ inhibitor 7 (compound 2) is a potent and orally active PI3Kγ inhibitor with IC₅₀ values of 4768, 878.1, 3.42, 355.2 nM for PI3Kα, PI3Kβ, PI3Kγ, PI3Kδ, respectively. PI3Kγ inhibitor 7 shows antitumor activity. PI3Kγ inhibitor 7 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

MEK/PI3K-IN-1 (compound 6r) is a potent MEK/PI3K inhibitor, with IC₅₀ values of 124 nM (MEK1), 130 nM (PI3Kα), and 236 nM (PI3Kδ), respectively. MEK/PI3K-IN-1 suppresses pAKT and pERK1/2 levels. MEK/PI3K-IN-1 shows anti-proliferative activity against tumor cell lines.

SRX3305 is an BTK/PI3K/BRD4 inhibitor with IC₅₀s of 6.5 nM, 15 nM, and 4 nM toward BTK, PI3Kɑ and PI3Kδ, respectively. SRX3305 attenuates chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) cell proliferation and promotes apoptosis in a dose-dependent fashion. SRX3305 yields potent anti-tumor effects but spares healthy bystander cells. SRX3305 inhibits the activation-induced proliferation of primary CLL cells in vitro and effectively blocks microenvironment-mediated survival signals. SRX3305 blocks CLL cell migration toward CXCL-12 and CXCL-13. SRX3305 maintains its anti-tumor effects in Ibrutinib (HY-10997)-resistant CLL cells. SRX3305 can be used for research in CLL, diffuse large B-cell lymphoma (DLBCL) and MCL.

CDK8-IN-19 (Compound 3d) is a CDK8 inhibitor with an IC₅₀ of 25.08 nM. CDK8-IN-19 has a broad-spectrum anticancer activity, such as leukemia, melanoma and breast cancer, without significant cytotoxic effect on the normal Vero cells (mean IC₅₀s of 2.87, 3.65, 3.79 and 45.48 μM, respectively).

PI3K/mTOR Inhibitor-8 (Compound 18b) is a PI3K and mTOR dual inhibitor with IC₅₀ values of 0.46 nM and 12 nM against PI3Kα and mTOR, respectively. PI3K/mTOR Inhibitor-8 induces HCT-116 cells apoptosis and arrests cell cycle at the G1/S phase.

XJTU-L453 is a PI3Kα inhibitor with an IC₅₀ value of 0.4 nM. XJTU-L453 can inhibit the proliferation of breast cancer cell lines T47D and MCF7, with IC₅₀ values of 0.2 μM and 0.5 μM, respectively. XJTU-L453 can inhibit the PI3K pathway, induce cell cycle arrest, and trigger cell apoptosis (apoptosis). XJTU-L453 also has antitumor activity in MCF7 xenograft mice.

Flupentixol is an orally active D₁/D₂ dopamine receptor antagonist and new PI3K inhibitor (PI3Kα IC₅₀=127 nM). Flupentixol shows anti-proliferative activity to cancer cells and induces apoptosis. Flupentixol can also be used in schizophrenia, anxiolytic and depressive research.

PI3Kα-IN-33 is an orally active and selective PI3Kα inhibitor with an IC₅₀ of 9.9 nM. PI3Kα-IN-33 blocks the PI3K/Akt/mTOR signaling pathway. PI3Kα-IN-33 induces apoptosis and triggers G2/M-phase arrest via Cyclin B1 and CDK1 downregulation. PI3Kα-IN-33 can be used for the research of colorectal cancer.

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.

PI3Kα-IN-27 (Compound 50b) is an orally active PI3K-α inhibitor, with an IC₅₀ of 40 nM. PI3Kα-IN-27 effectively inhibits PAK3, p110α, phospho-mTOR and phospho-ERK1/2. PI3Kα-IN-27 induces early Apoptosis. PI3Kα-IN-27 shows anticancer activity against pancreatic cancer, lung cancer, breast cancer.

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).

PI3Kα-IN-32 (Compound 11f) is a selective, orally active PI3Kα inhibitor, with an IC₅₀ of 26.3 nM against PI3Kα^H1047R. PI3Kα-IN-32 inhibits AKT phosphorylation. PI3Kα-IN-32 exhibits anticancer activity against breast cancer. PI3Kα-IN-32 can be used in the research of HR⁺/HER2^- breast cancer.

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.

PI3Kδ-IN-24 is a selective PI3Kδ inhibitor (IC₅₀ = 0.1 nM). PI3Kδ-IN-24 exhibits significant antiproliferative effects against PI3Kδ-overexpressing cancer cell lines. PI3Kδ-IN-24 reduces p-AKT levels and induces cell cycle arrest and apoptosis in tumor cells. PI3Kδ-IN-24 is useful in cancer research, such as diffuse large B-cell lymphoma (DLBCL).

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).

PI3Kα-IN-20 (compound 2) is a selective PI3Kα inhibitor.