Chemicals

LPA is a growth factor-like mediator and a ligand for multiple GPCR. The LPA2 GPCR mediates antiapoptotic and mucosal barrier-protective effectes in the gut. LPA GPCR activate antiapoptotic kinase pathways inhibit aopotosis promote cell regeneration and augment DNA repair. GRI977143 can be used for the attenuation of programmed cell death elicited by radiation and chemotherapeutic agents and also shows strong radioprotective action by rescuing cells from apoptosis and mice irradiated with lethal doses of γ-irradiation.

FPA-124 is a cell-permeable inhibitor of Akt (IC50 = 100 nM) binding to the PH and kinase domains. It inhibits cell proliferation in Colo357 BxPC3 BT20 and PC3 cancer cell lines with IC50 values ranging from 7-55 nM. FPA-124 inhibited tumor growth in mice with negligible toxicity.References Powered by Bioz See more details on Bioz1) V. Barve et al. "Synthesis Molecular Characterization and Biological Activity of Novel SyntheticDerivatives of Chromen-4-one in Human Cancer Cells" J. Med. Chem. 2006 49 3800-3808.2) Biscetti F. G. Straface et al. (2009). "Pioglitazone enhances collateral blood flow in ischemic hindlimb of diabetic mice through an Akt-dependent VEGF-mediated mechanism regardless of PPARgamma stimulation." Cardiovasc Diabetol 8: 49.3) Brito P. M. R. l. Devillard et al. (2009). "Resveratrol inhibits the mTOR mitogenic signaling evoked by oxidized LDL in smooth muscle cells." Atherosclerosis 205(1): 126.

KP372-1 directly inhibits the kinase activities of Akt PDK1 and Flt3 (Fms-like tyrosine kinase 3) which are aberrantly activated in acute myelogenous leukemia (AML). It is a cell permeant inhibitor that decreases the colony-forming ability of AML cells (IC50 < 200 nM) with minimal cytoxic effects on normal hematopoietic progenitor cells. KP372-1 has also been shown to suppress cell proliferation and induce apoptosis in thyroid cancer cells and gliobastoma. Provided as a 1:1 mixture of regioisomers.References Powered by Bioz See more details on Bioz1) M. Mandal et al. "The Akt Inhibitor KP372-1 Suppresses Akt Activity and Cell Proliferation and Induces Apoptosis in Thyroid Cancer Cells" Br. J. Cancer 2005 92 1899-1905.2) Z. Zeng et al "Simultaneous Inhibition of PDK1/AKT and Fms-Like Tyrosine Kinase 3 Signaling by a Small-Molecule KP372-1 Induces Mitochondrial Dysfunction and Apoptosis in Acute Myelogenous Leukemia." Cancer Res. 2006 66 3737-3746.

Wortmannin is a specific irreversible inhibitor of phosphatidylinositol 3-kinases (IC50 ~ 2-3 nM). It shows similar potency for all classes of PI3Ks.Publications Powered by Bioz See more details on Bioz1. Takahashi K Tanaka T Suzuki K. Directional control of WAVE2 membrane targeting by EB1 and phosphatidylinositol 3 4 5-triphosphate. Cell Signal. 2010;22(3):510-8.

LY294002 is a selective cell permeable potent and specific inhibitor of phosphatidylinositol 3-kinase (IC50 = 1.4 μM; purified PI 3-kinase). It does not significantly inhibit PKC PKA MAP kinase S6 kinase EGFrK c-src kinase PI 4-kinase DAG kinase or rabbit kidney ATPase at concentrations of 50 μM. Induces apoptosis. In intact neutrophils stimulated with fMet-Leu-Phe LY294002 completely abolished PI 3-kinase activity at 50 μM without cell toxicity.Publications Powered by Bioz See more details on Bioz1. Coronas-Serna JM Fernández-Acero T Molina M Cid VJ. A humanized yeast-based toolkit for monitoring phosphatidylinositol 3-kinase activity at both single cell and population levels. Microbial Cell. 2018;5(12):545-54.2. Chang P Walker MC Williams RS. Seizure-induced reduction in PIP3 levels contributes to seizure-activity and is rescued by valproic acid. Neurobiol Dis. 2014;62:296-306.3. Fernández-Acero T RodrÃguez-Escudero I Vicente F Monteiro MCn Tormo JR Cantiza

5-quinoxilin-6-methylene-1 3-thiazolidine-2 4-dione (AS605240) is an ATP-competitive inhibitor of PI3-Kγ (IC50 = 8 nM). It is selective for the γ-isoform (IC50: PI 3-Kα = 60 nM PI 3-Kβ = 270 nM PI 3-Kδ = 300 nM) and shows no notable activity against a wide array of protein kinases at 1 μM. In addition AS605240 suppresses the progression of joint inflammation in a mouse model of rheumatoid arthritis and suppresses inflammation in a mouse model of lupus.References Powered by Bioz See more details on Bioz1) M. Camps et al. "Blockade of PI3Kg suppresses joint inflammation and damage in mouse models of rheumatoid arthritis" Nature Medicine 2005 11 936-943.2) D.F. Barber et al. "PI3Kg inhibition blocks glomerulonephritis and extends lifespan in a mouse model of systemic lupus" Nature Medicine 2005 11 933-935.

5-(2 2-Difluoro-benzo[1 3]dioxol-5-ylmethylene)-thiazolidine-2 4-dione (AS604850) is an inhibitor of PI 3-Kγ with an IC50 = 250 nM. AS604850 is selective for the γ-isoform (IC50: PI 3-Kα = 4.5 μM PI 3-Kβ PI 3-Kδ > 20 μM) and shows no notable activity against a wide array of protein kinases at 1 μM.References Powered by Bioz See more details on Bioz1) M. Camps et al. "Blockade of PI3Kg suppresses joint inflammation and damage in mouse models of rheumatoid arthritis" Nature Medicine 2005 11 936-943.

PI-103 is a selective inhibitor for the α-isoform of PI 3-Kinase (IC50: PI 3-Kα = 8 nM PI 3-Kβ = 88 nM PI 3-Kδ = 48 nM PI 3-Kγ = 150 nM). It is also inhibits DNA-PK (IC50 = 2 nM) and mTOR1 and mTOR2 (IC50 = 20 & 83 nM). PI-103 shows little activity against a wide array of protein kinases at 10μM. PI-103 blocks glioma proliferation by blocking the PI 3-K/Akt pathway in vitro and in vivo.References Powered by Bioz See more details on Bioz1) Fan Q. et al. (2006) ."A dual PI3 kinase/mTOR inhibitor reveals emergent efficacy in glioma." Cancer Cell 9: 341-349.2) Smit M. A. T. R. Geiger et al. (2009). "A Twist-Snail axis critical for TrkB-induced epithelial-mesenchymal transition-like transformation anoikis resistance and metastasis." Mol Cell Biol 29(13): 3722-37.3) Gursel D. B. Y. S. Connell-Albert et al. (2011). "Control of proliferation in astrocytoma cells by the receptor tyrosine kinase/PI3K/AKT signaling axis and the use of PI-103 and TCN as potential anti-astro

3-(4-Morpholinothieno[3 2-d]pyrimidin-2-yl)phenol is a selective inhibitor for the α-isoform of PI 3-Kinase (IC50: PI 3-Kα = 2 nM PI 3-Kβ = 16 nM PI3-Kγ = 660 nM PI3KC2β = 220 nM)). It showed >1000-fold selectivity vs. protein kinases such as PKA KDR PKCa and E/CDK2 (IC50 = 91 3.4 466 288 μM). It inhibited proliferation of A375 melanoma cells at 580 nM. Also known as PI3-K Inhibitor 2 PIK2.References Powered by Bioz See more details on Bioz1) M. Hayakawa et al. "Synthesis and biological evaluation of 4-morpholino-2-phenyl quinazolines and related derivatives as novel PI3 kinase p110a inhibitors" Bioorg. Med. Chem. 2006 14 6847-6858.