phosphatidylinositol 3-kinase

RIP2 Kinase Inhibitor 3 is a potent and selective inhibitor of RIP2 with an IC50 of 1 nM.

Multi-kinase-IN-3 (compound 2) is a potent inhibitor of angiokinase and inhibits VEGFR-2 (IC50: 58.3 nM) and PDGFRβ (IC50: 55 nM).

MET kinase-IN-3 is a potent, orally active MET inhibitor (IC50: 9.8 nM) that exhibits good broad-spectrum anti-proliferative effects on cancer cells.

TIE-2/VEGFR-2 kinase-IN-3, a benzimidazole derivative, serves as a potent inhibitor of the tyrosine kinase receptors TIE-2 and VEGFR-2, exhibiting IC50 values of 6.9 nM and 3.5 nM, respectively. This compound is useful for angiogenesis research [1].

Aurora kinase inhibitor-3 (Aurora Kinase Inhibitor III) is a potent inhibitor of Aurora A kinase (IC50 = 42 nM).1 It is selective for Aurora A over BMX, BTK, IGF-1R, c-Src, TRKB, SYK, and EGFR.

Casein kinase 1δ-IN-3 (Casein kinase 1δ-IN-3) (Compound 23a) is a casein kinase 1 delta (CK1d) inhibitor with a pIC50 of 6.5376 M.

Pim-1 kinase inhibitor 3 (Compound H5) is a potent inhibitor of Pim-1 kinase, demonstrating an inhibitory concentration (IC50) of 35.13 nM [1].

IRE1α kinase-IN-3 is a potent, ATP-competitive inhibitor of IRE1α (Ki: 480 nM).

Casein Kinase Substrates 3 is a substrate of casein kinase.

1. ISOGINKGETIN (4',4'''-Dimethylamentoflavone), a compound derived from the leaves of Ginkgo biloba, to up-regulate adiponectin secretion with potency comparable to that of rosiglitazone, a known modulator of adiponectin production. 2. Isoginkgetin has anti-tumor activity, the mechanistic basis is splicing inhibition , thus, pre-mRNA splicing inhibitors may represent a novel avenue for development of new anti-cancer agents.3. Isoginkgetin can inhibit tumor cell invasion by regulating phosphatidylinositol 3-kinase/Akt-dependent matrix metalloproteinase-9 expression. 4. Isoginkgetin (0.3mg/kg ip for 3d) can reduce the level of O2·- in plasma and erythroeyte and sometimes increase the activity of SOD in anoxic rats, the action being stronger than aspirin.

mTOR inhibitor 9b is an enzyme inhibitor of protein kinase mTOR he phosphatidylinositol 3-kinase PIK3CA with IC50s of 0.76 nm and 1.262 µM, respectively.mTOR inhibitor 9b possesses anticancer activity and can be used to study leukemia, skin, breast, lung and colon cancers.

LY-294002 hydrochloride (NSC 697286) is a synthetic molecule inhibitor of PI3Kα/δ/β (IC50: 0.5/0.57/0.97 μM, in cell-free assays); more stable than Wortmannin in solution, and also is a blocker of autophagosome formation.

mTOR inhibitor 9d is a dual inhibitor of the protein kinases mTOR and PI3K with an mTOR IC50 value of 0.31 nm, and can be used for the treatment of leukemia, skin cancer, breast cancer, lung cancer and colon cancer.

Taselisib (GDC-0032) is an orally bioavailable inhibitor of the class I phosphatidylinositol 3-kinase (PI3K) alpha isoform (PIK3CA), with potential antineoplastic activity.

PI3K Inhibitor ZSTK474 is an orally available, s-triazine derivative, ATP-competitive phosphatidylinositol 3-kinase (PI3K) inhibitor with potential antineoplastic activity.

Inostamycin A is a bacterial metabolite that has been found inStreptomycesand has anticancer activity.1It is an inhibitor of CDP-diacylglycerol:inositol 3-phosphatidyltransferase (IC50= 0.02 μg/ml in A431 cell membranes) and is selective for CDP-diacylglycerol:inositol 3-phosphatidyltransferase over phospholipase C (PLC) and phosphatidylinositol kinase at 10 μg/ml.2Inostamycin A decreases viability of YCU-T892, KCC-TC873, KB, HSC-4, and YCU-T891 oral squamous cell carcinoma (OSCC) cells in a concentration-dependent manner.3It induces cell cycle arrest in the G1phase in HSC-4 cells when used at a concentration of 250 ng/ml and induces apoptosis in Ms-1 small cell lung cancer cells at 300 ng/ml.3,4Inostamycin A also reduces levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 and inhibits EGF-induced migration of HSC-4 cells.5 1.Imoto, M., Umezawa, K., Takahashi, Y., et al.Isolation and structure determination of inostamycin, a novel inhibitor of phosphatidylinositol turnoverJ. Nat. Prod.53(4)825-829(1990) 2.Imoto, M., Taniguchi, Y., and Umezawa, K.Inhibition of CDP-DG: inositol transferase by inostamycinJ. Biochem.112(2)299-302(1992) 3.Baba, Y., Tsukuda, M., Mochimatsu, I., et al.Cytostatic effect of inostamycin, an inhibitor of cytidine 5'-diphosphate 1,2-diacyl-sn-glycerol (CDP-DG): inositol transferase, on oral squamous cell carcinoma cell linesCell Biol. Int.25(7)613-620(2001) 4.Imoto, M., Tanabe, K., Simizu, S., et al.Inhibition of cyclin D1 expression and induction of apoptosis by inostamycin in small cell lung carcinoma cellsJpn. J. Cancer Res.89(3)315-322(1998) 5.Baba, Y., Tsukuda, M., Mochimatsu, I., et al.Inostamycin, an inhibitor of cytidine 5'-diphosphate 1,2-diacyl-sn-glycerol (CDP-DG): Inositol transferase, suppresses invasion ability by reducing productions of matrix metalloproteinase-2 and -9 and cell motility in HSC-4 tongue carcinoma cell lineClin. Exp. Metastasis18(3)273-279(2000)

WAY-299017 is a potent and selective UPPS inhibitor for the treatment of bacterial infections.

D-myo-Inositol-1,4,5,6-tetrahosphate (sodium salt) (Ins(1,4,5,6)-P4) is one of several different inositol oligophosphate isomers implicated in signal transduction. Production of Ins(1,4,5,6)-P4 by intestinal epithelial cells increases approximately 2-14 fold, depending on the strain and incubation time, following infection with Salmonella.[1] D-myo-Inositol-1,4,5,6-tetraphosphate (sodium salt) (Ins(1,4,5,6)-P4) is one of several different inositol oligophosphate isomers implicated in signal transduction. Production of Ins(1,4,5,6)-P4 by intestinal epithelial cells increases approximately 2-14 fold, depending on the strain and incubation time, following infection with Salmonella. Ins(1,4,5,6)-P4 antagonizes epidermal growth factor (EGF) signalling through the phosphatidylinositol 3-kinase pathway. Ins(1,4,5,6)-P4 (tested as the D/L racemic mixture) is ~1,000-fold less potent than Ins(1,4,5)-P3 at initiating Ca2+ release when injected into Xenopus oocytes.[2]

Phosphatidylinositol 4,5-bisphosphate (L-alpha-Phosphatidylinositol-4,5-bisphosphate), serving as a critical phospholipid in cell membranes, functions as a substrate for both phospholipase C (PLC) and phosphoinositide 3-kinase (PI3K), acting as a primary messenger [1] [2] [3].

Phosphatidic acid is a phospholipid and an intermediate in glycerolipid biosynthesis. It is a transient intermediate in the synthesis of various phospholipid species that is synthesized de novo in cells via multiple routes, including the glycerol-3 phosphate and dihydroxyacetone phosphate pathways, enzymatic conversion of phosphatidylcholine by phospholipase D, and acetylation of lysophosphatidic acid by lysoPA-acyltransferase, among others. It has roles in shaping cellular membranes, cellular signaling, vesicle fission and fusion, as well as mitochondrial division and fusion. It stimulates respiratory burst in neutrophils independent of diacylglycerol and activates monoacylglycerol acyltransferase, phospholipase C (PLC), Ras, and phosphatidylinositol 4-phosphate (PIP4) kinase in several cell lines. Phosphatidic acids (egg) is a mixture of phosphatidic acids isolated from chicken egg with fatty acids of variable chain lengths.

PtdIns-(3,4,5)-P3 (PIP3) serves as an anchor for the binding of signal transduction proteins bearing pleckstrin homology (PH) domains such as phosphatidylinositol 3-kinase (PI3K) or PTEN. Protein binding to PIP3 is important for cytoskeletal rearrangement and membrane trafficking and initiates an intricate signaling cascade that has been implicated in cancer. 3,5-dimethyl PIT-1 is a dimethyl analog of PIT-1, the selective inhibitor of PIP3/Akt PH domain binding, that is designed for more favorable solubility in vivo. 3,5-dimethyl PIT-1 inhibits PI3K/Akt signaling (IC50 = 27 μM), suppressing PI3K-PDK1-Akt-dependent phosphorylation, which has been shown to reduce cell viability and induce apoptosis in PTEN-deficient U87MG glioblastoma cells (IC50 = 36 μM). 4T1 breast cancer growth is significantly attenuated in BALB/c mice with a dose of 1 mg/kg of 3,5-dimethyl PIT-1 per day.

Vulolisib is an orally active and potent inhibitor of phosphatidylinositol 3 kinase (PI3K), acting on PI3Kα (IC50: 0.2 nM), PI3Kβ (IC50: 168 nM), PI3Kγ (IC50: 90 nM), PI3Kδ (IC50: 49 nM). activity and exhibits anti-proliferative activity against cancer cells.

Psoralidin inhibits Akt phosphorylation and phosphatidylinositol 3-kinase activation and transcriptionally. Psoralidin possesses anticancer and chemopreventive properties.

Potent cdk1 inhibitor (IC50 = 25 nM). Reduces Akt phosphorylation and increases mitochondrial damage in leukemia cells in vitro in combination with LY 294002. Yu et al (2013) The lethal effects of pharmacological cyclin-dependent kinase inhibitors in human leukemia cells proceed through a phosphatidylinositol 3-kinase/Akt-dependent process. Cancer Res. 63 1822 PMID:12702569 |Furet et al (2000) Structure-based design of potent CDK1 inhibitors derived from olomoucine. J.Comput.Aided Mol.Des. 14 403 PMID:10896313

Dehydroglyasperin D exhibits anticancer, anti-inflammatory, anti-obesity, antioxidant and anti-aldose reductase effects, it inhibits the proliferation of HT-29 human colorectal cancer cells through direct interaction with phosphatidylinositol 3-kinase; it also mediates suppression of both COX-2 expression and the MLK3 signalling pathway through direct binding and inhibition of MLK3. Dehydroglyasperin D shows strong ferric reducing activities and effectively scavenged DPPH, ABTS(+), and singlet oxygen radicals.

Dezapelisib is an orally bioavailable, selective inhibitor of the delta isoform of the 110 kDa catalytic subunit of class I phosphoinositide-3 kinases (PI3K). INCB040093 prevents both the production of the second messenger phosphatidylinositol-3,4,5-trisp

PIKfyve-IN-1 is a cell-active and highly potent chemical probe that can be used for the PIKfyve research in virology. PIKfyve-IN-1 inhibits phosphatidylinositol-3phosphate 5-kinase (PIKfyve) (IC 50 = 6.9 nM)[1].

Omipalisib (GSK2126458) is a small-molecule pyridylsulfonamide inhibitor of phosphatidylinositol 3-kinase (PI3K) with potential antineoplastic activity.

Halenaquinone is a phosphatidylinositol 3-kinase inhibitor. Halenaquinone specifically inhibits the secondary DNA binding of RAD51. Halenaquinone inhibits RANKL-induced osteoclastogenesis. Halenaquinone induces apoptosis in PC12 cells.

PIK-108 is an allosteric inhibitor of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunits β and δ (PI3Kβ/δ).

PKI-179 is a potent, orally active compound that functions as a dual PI3K/mTOR inhibitor. It demonstrates IC50 values of 8 nM for PI3K-α, 24 nM for PI3K-β, 74 nM for PI3K-γ, 77 nM for PI3K-δ, and 0.42 nM for mTOR. Additionally, it is effective against E545K and H1047R mutations, with IC50s of 14 nM and 11 nM, respectively. In vivo studies have shown that PKI-179 possesses anti-tumor capabilities[1][2].

PARP/PI3K-IN-1 is a novel dual poly (ADP-ribose) polymerase (PARP) and phosphatidylinositol 3-kinase (PI3K) dual inhibitor with anticancer, antitumour and antiproliferative activities for the study of breast, pancreatic and lung cancers.

GSK-F1 (PI4KA inhibitor-F1) is a novel potent PI4KA inhibitor.

PI3K inhibitor C 96 is an inhibitor of phosphatidylinositol 3-kinase. It shows effective activity against multiple myeloma in vitro and in vivo.

PI3K-IN-19 hydrochloride (WO2017153220, step 5) acts as a phosphatidylinositol-3-kinase (PI3K) inhibitor.

PI4KIIIbeta-IN-9 is a potent inhibitor of PI4KIIIβ(IC50 of 7 nM). .

PIK-93 is the first potent, synthetic PI4K inhibitor with IC50 of 19 nM; inhibits PI3Kα with IC50 of 39 nM.

DS-7423 is a dual PI3K and mTOR inhibitor, with IC50 values of 15.6 nM, 34.9 nM for PI3Kα and mTOR, respectively. DS-7423 possesses anti-tumor activity[1][2]. DS-7423 increases TP53 expression, the level of p-TP53 on Ser-46, and induced apoptosisrelated TP53 target genes (TP53AIP1 and PUMA) in OCCC cells[1].DS-7423 also inhibits other isoforms of class I PI3K (IC50 values: PI3Kβ = 1,143 nM; PI3Kγ = 249 nM; PI3Kδ = 262 nM)[2]. [1]. Katsutoshi Oda, et al. Characterization of TP53 and PI3K signaling pathways as molecular targets in gynecologic malignancies. J Obstet Gynaecol Res. 2016 Jul;42(7):757-62.[2]. Tomoko Kashiyama, et al. Antitumor activity and induction of TP53-dependent apoptosis toward ovarian clear cell adenocarcinoma by the dual PI3K/mTOR inhibitor DS-7423. PLoS One. 2014 Feb 4;9(2):e87220.

RV-1729, a phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) inhibitor, is used potentially for the treatment of asthma.

WJD008 is a dual inhibitor of phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin. WJD008 prevents PI3K signaling and inhibits the proliferation of transformed cells with oncogenic PI3K mutant. WJD008 has antiproliferative and anticlonogeni

Zandelisib is an inhibitor of phosphatidylinositol 3-kinase (PI3K)(p110δ, IC50 of 3.5 nM), and with antineoplastic activity.

Demethoxyviridiol is a mycotoxin that inhibits phosphatidylinositol 3-kinase (PI3K).

Orobol (3’,4’,5,7-tetrahydroxy-isoflavon) is an inhibitor of tyrosine-specific protein kinase and phosphatidylinositol turnover. Orobol inhibits PI3K isoforms with IC50s of 3.46-5.27 μM for PI3K α/β/γ/K/δ. Orobol exhibits anti-skin-aging and anti-obesity effects.

AS2541019 is a selective Phosphatidylinositol-3-kinase p110δ (PI3Kδ) inhibitor.

17β-Hydroxywortmannin is an orally active phosphatidylinositol-3-kinase (PI-3-kinase) inhibitor, exhibiting an IC50 of 0.5 nM and notably suppresses osteoclast resorption at an IC50 of 10 nM. Additionally, it demonstrates antitumor activity.

LY303511, a structural analog of LY294002, selectively inhibits mTOR-dependent phosphorylation of S6K, unlike its counterpart, which acts as a phosphatidylinositol 3-kinase (PI3K) inhibitor. It effectively reduces cell proliferation in human lung epithelial adenocarcinoma cells by hindering G2/M phase progression and suppressing casein kinase 2 activity. Additionally, LY303511 enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) sensitivity in HeLa cells resistant to TRAIL-induced apoptosis and blocks voltage-gated potassium (Kv) channels.

The PtdIn phosphates play an important role in the generation and transduction of intracellular signals. PtdIns-(3,4,5)-P3-biotin is an affinity probe which allows the PIP3 to be detected through an interaction with the biotin ligand. This design allows PtdIns-(3,4,5)-P3-biotin to serve as a general probe for any protein with a high affinity binding interaction with inositol-(3,4,5)-triphosphate phospholipids, such as phosphatidylinositol 3-kinase, PTEN, or PH-domain-containing proteins.

Phosphatidylinositol 3-kinase (PI3K) catalyzes the phosphorylation of the 3' hydroxyl position of PIs to produce the second messengers PtdIns-(3,4)-P2 and PtdIns-(3,4,5)-P3. PI3Kα, β, and δ are class 1A enzymes composed of p110 and p85 subunits, whereas PI3Kγ is a class 1B PI3K composed of a p110 catalytic subunit and a p101 or p84 regulatory subunit. PI3Kα inhibitor 2 is a selective inhibitor of PI3Kα with IC50 values of 2, 16, 660, and 220 nM for the α, β, γ, and 2Cβ isoforms, respectively. It inhibits PKA, KDR, PKCα, and cyclin E/Cdk2 significantly less effectively (IC50 = 91, 3.4, 466, and 28 μM, respectively). PI3Kα inhibitor 2 inhibits A375 melanoma cell proliferation with an IC50 value of 580 nM.

PI-828 is a phosphatidylinositol 3-kinase (PI3K) inhibitor, which is widely used to study the physiological function of PI3K and also promotes stem cell differentiation into mesoderm.

PH11 is a novel Focal Adhesion Kinase (FAK) inhibitor. PH11 restores TRAIL apoptotic pathway in PANC-1 cells through down-regulation of c-FLIP via inhibition of FAK and the phosphatidylinositol-3 kinase (PI3K)/AKT pathways. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) emerges as one of the most-promising experimental cancer therapeutic drugs and is currently being tested in clinical trials. However, both intrinsic and acquired resistance of human cancer cells to TRAIL-induced apoptosis poses a huge problem in establishing clinically efficient TRAIL therapies.