PI3K Inhibitor

PI3Kδ-IN-9 is a selective PI3Kδ inhibitor with an IC₅₀ value of 3.8 nM.

Vps34-IN-3 is a potent, selective, and orally bioavailable VPS34 kinase inhibitor.

MDVN1003 is a Bruton's tyrosine kinase (BTK) and phosphatidylinositol-3-kinase delta (PI3Kδ) dual inhibitor which prevents the activation of B cells and inhibits the phosphorylation of protein kinase B (AKT) and extracellular signal-regulated kinase 1/2 (ERK 1/2). MDVN1003 can be used for non-Hodgkin’s lymphoma (NHL) research.

Endoxifen-d₅ (Z-isomer) is the deuterated-labeled Endoxifen (Z-isomer methanesulfonate) (HY-18719H). Endoxifen-d₅ Z-isomer is an orally active selective PKCβ1 inhibitor with an IC₅₀ of 360 nM against human PKCβ1. It also acts as an estrogen receptor modulator and antiestrogen. Endoxifen-d₅ Z-isomer binds to and blocks ERα, ERβ and PKCβ1, inhibits estrogen and PI3K/AKT/mTORC1 signaling pathways, suppresses the expression of genes associated with cell cycle, cell proliferation and extracellular matrix remodeling, and induces apoptosis, reactive oxygen species (ROS) production and hypoxic features. Endoxifen-d₅ Z-isomer inhibits tumor growth in breast tumor and glioblastoma models, reduces bone turnover and blood lipid levels, and does not require metabolism via CYP2D6. It can be used in research related to ER⁺ breast cancer, invasive breast cancer, glioblastoma multiforme, type I bipolar disorder, desmoid tumor, gynecological malignancies, melanoma and hormone receptor-positive solid tumors

Leupeptin is a broad-spectrum protease inhibitor. By inhibiting the activation of the PTEN/PI3K/Akt/NF-κB/ERK1/2/p38 signaling pathway, Leupeptin significantly reduces LPS-induced NO and ROS production, mitochondrial membrane potential hyperpolarization, phagocytic activity, pro-inflammatory cytokine release, and M1 polarization in mouse peritoneal macrophages, and reverses autophagic flux impairment. It also decreases Concanavalin A (HY-P2149)-induced proliferation index of mouse splenic lymphocytes and the Th1/IL-10 and Th2/IL-10 cytokine ratios, thereby modulating innate and adaptive immune responses. Leupeptin inhibits blood coagulation and tumorigenesis in mouse skin. Leupeptin can be used in research on chronic inflammatory diseases and skin tumorigenesis.

PRT543 is an orally active selective PRMT5 inhibitor. PRT543 reduces intracellular symmetric dimethylarginine (sDMA) levels, downregulates the expression of genes related to DNA damage repair and DNA replication pathways, and induces abnormal alternative splicing. PRT543 inhibits the MYB, NOTCH1 and PI3K/AKT signaling pathways, promotes nuclear translocation of FOXO1, upregulates the pro-apoptotic protein BAX, and enhances cellular sensitivity to BCL-2 inhibition. PRT543 disrupts the normal RNA splicing process and exerts a synthetic lethal effect on myeloid tumor cells carrying splicing factor mutations. PRT543 can be used in research related to various cancers including breast cancer, ovarian cancer and acute myeloid leukemia.

PWT-33597 (VDC-597) free base is a dual inhibitor of PI3Kα and mTOR, which can effectively block the signaling downstream of PI3K and mTOR. PWT-33597 free base is capable of inducing tumor cell apoptosis and inhibiting tumor growth. PWT-33597 free base has anti-tumor activity and can be used in the research of tumors such as renal cell carcinoma.

GSK251 is a highly potent, highly selective, orally bioavailable inhibitor of PI3Kδ with a novel binding mode.

Taurolithocholic acid-d₄ (sodium) is the deuterium labeled Taurolithocholic acid (sodium salt). Taurolithocholic acid sodium is an orally active bile acid and antiviral agent. Taurolithocholic acid sodium upregulates FADS2 by activating the TGR5-PI3K/AKT-SREBP2 signaling axis, inhibits SFTSV-induced ferroptosis, viral replication and viral entry of HBV/HDV, while reducing the release of IL-1β, lipid ROS and LDH. While exerting antiviral protective effects, Taurolithocholic acid sodium also stimulates the recycling of hepatocellular membrane transporters, impairs canalicular bile acid secretion function, and induces hepatocyte cholestasis, apoptosis and acute hepatocellular injury. Taurolithocholic acid sodium serves as an experimental model compound for hepatocellular cholestasis. At concentrations ≤200 μM, Taurolithocholic acid sodium shows no cytotoxicity and does not activate the interferon pathway. Taurolithocholic acid sodium not only protects mice from lethal SFTSV infection but also is suitable for studies related to severe fever with thrombocytopenia syndrome and cholestasis.

PWT-33597 (VDC-597) is a dual inhibitor of PI3Kα and mTOR, which can effectively block the signaling downstream of PI3K and mTOR. PWT-33597 is capable of inducing tumor cell apoptosis and inhibiting tumor growth. PWT-33597 has anti-tumor activity and can be used in the research of tumors such as renal cell carcinoma.

Zinilisib (Zinilisibum) is a PI3K inhibitor. Zinilisib potently inhibits the phosphorylation of AKT in cells expressing mutant PI3Kα^H1047R and wild-type PI3Kα, with IC₅₀ values of 1-500 nM and 2-15 μM, respectively. Zinilisib can be used in breast cancer-related research.

PI3K-IN-63 is a selective PI3Kα inhibitor with a K_i of 0.35 nM against human targets. PI3K-IN-63 inhibits the phosphorylation of AKT at the S473 site in cellular assays. PI3K-IN-63 reduces the viability of non-small cell lung cancer cell lines carrying PIK3CA mutations. PI3K-IN-63 can be used in studies related to non-small cell lung cancer.

Amdizalisib (HMPL-689) is a PI3K inhibitor and used for the research of inflammatory disease, autoimmune disease or cancer.

FKL-137 is a GLUT1 and PI3K/AKT signaling pathway inhibitor. FKL-137 binds to GLUT1, reduces glucose uptake and lactate secretion, downregulates glucose metabolism-related proteins, and inhibits erythroleukemia cell proliferation. FKL-137 downregulates PI3K, p-PI3K, AKT, p-AKT levels, disrupts the PI3K/AKT-GLUT1 positive feedback loop, and suppresses erythroleukemia cell proliferation. FKL-137 induces apoptosis via upregulated Bax, Cleaved-PARP and downregulated Bcl-2, PARP. FKL-137 can be used for the research of erythroleukemia.

ATM Inhibitor-3 (compound 34) is a potent and selective ATM inhibitor, with an IC₅₀ of 0.71 nM. ATM Inhibitor-3 shows inhibition of PI3K kinases family. ATM Inhibitor-3 exhibits favorable metabolic stability.

Levalbuterol (Levosalbutamol) hemitartrate is a β₂-adrenergic receptor agonist and PI3K inhibitor. Levalbuterol hemitartrate inhibits PI3K activity, reduces NF-κB and Rb protein expression, activates the cAMP/PKA pathway, and stimulates cAMP release. Levalbuterol hemitartrate relaxes airway smooth muscle, reduces intracellular calcium levels, and inhibits spasmogen-induced contractions. Levalbuterol hemitartrate can be used for the research of moderate-to-severe asthma.

ATM Inhibitor-4 (compound 39) is a potent and selective ATM inhibitor, with an IC₅₀ of 0.32 nM. ATM Inhibitor-4 shows stronger inhibition of PI3K kinases family. ATM Inhibitor-4 shows a full inhibition of mTOR at 1 μM. ATM Inhibitor-4 exhibits favorable metabolic stability.

PI3K/mTOR Inhibitor-3 (compound 12), an imidazoline, is a potent PI3K and mTOR dual inhibitor. PI3K/mTOR Inhibitor-3 has anti-cancer activity.

Pan-RAS-IN-8 (Page 152, third row, third from left to right) is a pan-RAS inhibitor. Pan-RAS-IN-8 blocks the binding of RAS to downstream effector molecules by forming a ternary complex, thereby inhibiting the activation of the MAPK and PI3K-AKT signaling pathways. Pan-RAS-IN-8 can be used for the research of cancer, inflammatory diseases and autoimmune diseases.

PI3K/mTOR-IN-20 is a selective dual PI3K/mTOR inhibitor. PI3K/mTOR-IN-20 demonstrates nanomolar antiproliferative effects with IC₅₀s of 0.380 and 0.090 μM for MRC-5 and Mlg2908 cells. PI3K/mTOR-IN-20 reduces Ashcroft scores, hydroxyproline content, collagen deposition, and downregulates fibrosis-related proteins, while restoring lung architecture in a Bleomycin-induced pulmonary fibrosis model. PI3K/mTOR-IN-20 shows a favorable safety profile with steady weight recovery and no distinct liver or kidney toxicity. PI3K/mTOR-IN-20 can be used for fetal lung fibroblasts research.