|Zandelisib is a potent and selective inhibitor of phosphatidylinositol 3-kinase (PI3K) with IC50 of 3.5 nM for p110δ.
|XL147 is a potent, orally bioavailable inhibitor of the class I PI3K family of lipid kinases with IC50 values of 39 nM383 nM36 nM23 nM for PI3K, respectively and less potent to PI3K.
|Vps34-IN1 is a potent inhibitor of the class III phosphoinositide 3-kinase (PI3K) vacuolar protein sorting 34 (Vsp34) with IC50 of 15 nM.
|Voxtalisib is a potent and highly selective inhibitor of class I PI3Ks with IC50 of 39110943 nM for PI3K, also inhibits mTOR with IC50 of 160-910 nM.
|UNBS5162 is a naphthalimide and a hydrolysis product of UNBS3157 that decreases CXCL chemokine expression in experimental prostate cancers and the mean antiproliferative activity IC50 value is 179 M for 9 cancer cell lines
|Umbralisib tosylate is a novel phosphatidylinositol 3-kinase delta (PI3Kdelta) inhibitor under development at TG Therapeutics. In 2021, the product received accelerated approval in the U.S. for the oral, once-daily treatment of adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one prior anti-CD20-based regimen and for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least three prior lines of systemic therapy. Launch took place short after. In 2021, TG Therapeutics completed a rolling submission in the U.S in combination with ublituximab for the treatment of chronic lymphocytic leukemia (CLL). The product is in phase III clinical trials, as monotherapy or in combination with ublituximab, for the treatment of CLL. The product is also in phase II/III clinical trials, as monotherapy or in combination with ublituximab, for the treatment of relapsed or refractory small lymphocytic lymphoma and B-cell lymphomas, including MZL, FL, diffuse large B-cell lymphoma and mantle cell lymphoma. The company refers to the combination regimen of ublituximab and TGR-1202 as TG-1303. The drug is also in phase II clinical development for the treatment Waldenstrom macroglobulinemia. Phase I clinical trials are ongoing for the treatment of Hodgkin's lymphoma. Phase I clinical trials were completed for the treatment of patients with select relapsed or refractory solid tumors, such as adenocarcinoma of the pancreas, adenocarcinoma of the colon, rectum, gastric and GE junction cancer, and GI Stromal Tumor (GIST). In 2016, orphan drug designation was assigned to the compound in the U.S. for the treatment of CLL. In 2017, additional orphan drug designation was granted in the U.S. for the treatment of CLL and DLBCL, in combination with ublituximab. In January 2019, the FDA granted breakthrough therapy designation to the product for the treatment of adult patients with MZL who have received at least one prior anti-CD20 regimen. The compound was granted additional orphan drug designation in the U.S. for the treatment of treatment of nodal, extranodal, and splenic MZL in 2019, and for the treatment of FL in 2020. Originated by Rhizen Pharmaceuticals, the product was jointly developed by Rhizen Pharmaceuticals and TG Therapeutics since 2012. In 2014, exclusive global development and commercialization rights (excluding India) were licensed to TG Therapeutics. In 2020, the product received fast track designation in US by TG Therapeutics for the treatment of adult patients with CLL in combination with ublituximab.
|TC KHNS 11 is a potent and selective PI 3-kinase δ inhibitor that is orally bioavailable.
|Stressin-1 is a Phosphatidylinositol 3-Kinase (PI3K) activator.
|SRX3207 is an orally active dual Syk/PI3K inhibitor with IC50 value of 30nM for Syk. It potently blocks phosphorylation of Syk at 348 site and Y525/526 site. SRX3207 reduced immunosuppressive macrophage polarization and increased infiltration and cytotoxicity of CD8+ T cells in LLC tumors and increased expression of Ifng and Gzmb in 3207 treated LLC tumors.
|Sophocarpine, a natural product isolated and purified from the herb of Sophora alopecuroidos L., with anti-viral, anti-cachectic and anti-inflammatory effects, can alleviate liver fibrosis mainly by inhibiting the TLR4 pathway, it may be a potential chemotherapeutic agent for chronic liver diseases, ameliorate the ischemic injury induced by transient focal cerebral ischemia in rats and that this neuroprotective effect may be related to the anti-ASIC1 channel and anti-apoptotic action of sophocarpine, and also alleviate hepatocyte steatosis and the potential mechanism may be the activated signaling pathway of AMPK.
|Sophocarpine is a naturally-occuring HERG K channel blocker with IC50 ranging in 100-300 M found from plant Sophora flavescens
|SF2523 blocks BRD4 binding to MYCN promoter PS1/PS2.
|Quercetin Dihydrate inhibits various proteins including tyrosine protein kinase, mitochondrial phospholipase A2 and phosphodiesterases. It is a flavonoid with anticancer activity via suppressing type II estrogen receptors and blocking cell cycle progression. Quercetin could be found in a wide variety of plant-based foods, such as apples, onions, berries, and red wine etc..
|PWT33597 is a dual inhibitor of PI3K alpha and mTOR with selectivity for PI3K alpha (IC50 = 26 nM) over PI3K delta (IC50 = 291 nM) but also displaying activity against mTOR in biochemical assays (IC50 = 21 nM). It had good pharmacokinetic properties in multiple preclinical species.
|PIK-75 is a selective p110α inhibitor with IC50 of 5.8 nM with 200-fold more potently than p110β, and also potently inhibits DNA-PK with IC50 of 2 nM.
|PI3K/mTOR Inhibitor-2 is a dual pan-PI3K/mTOR inhibitor with IC50 values of 3.4/34/16/1nM for PI3Kα/PI3Kβ/PI3Kδ/PI3Kγ and 4.7 nM for mTOR, respectively.
|PI3K-IN-2 (compound 10) is a potent and orally active PI3Kβ/δ (IC50=7.1/8.6 nM) inhibitor with excellent selectivity versus PI3Kσ and PI3Kγ (IC50=13/190 nM, respectively).
|PI-828 is a dual PI3K and casein kinase 2 (CK2) inhibitor with IC50s of 173 nM, 149 nM, and 1127 nM for p110α, CK2, and CK2α2 in lipid kinase assay, respectively.
|PI-103 is a potent inhibitor with low IC50 values against recombinant PI3K isoforms p110alpha (IC50= 2 nM), p110beta (IC50= 3 nM), p110delta (IC50= 3 nM), and p110gamma (IC50= 15 nM), less potent to mTOR/DNA-PK with IC50 of 30 nM/23 nM. It blocks autophagic flux.
|MTX-211 is a dual inhibitor of EGFR and PI3K, used for the treatment of cancer and other diseases.
|MLN1117 is a selective p110 inhibitor with IC50 of 15 nM.
|Hexadecyl (2-(trimethylammonio)ethyl) phosphate
|Miltefosine is a mult-target inhibitor which can inhibit Akt, PI3K and PKC.
|ME-401 is a potent and selective P110δ inhibitor.
|LY294002 is the first synthetic molecule known to inhibit PI3Kα/δ/β with IC50 of 0.5 μM/0.57 μM/0.97 μM in cell-free assays. It is an early-stage autophagy inhibitor and also inhibits CK2.
|Linarin, a natural product isolated and purified from the herb of Uncaria sinensis (Oliv.) Havil., prevents a beta-induced neurotoxicity through the activation of PI3KAkt, which subsequently inhibits GSK-3b and up-regulates Bcl-2.
|LAS191954 is a Potent, Selective, and Orally Available PI3Kδ Inhibitor for the Treatment of Inflammatory Diseases. LAS191954 showed PI3Kdelta IC50 = 2.6 nM; M-CSF p-Akt IC50 = 7.8 nM; % Metabolism (R/H) = 20/16; PK i.v. t1/2 (R/D) = 3.1 h/10.2h. LAS191954 showed efficacy at significantly lower doses than Idelalisib. LAS191954 showed a potency on the target of 2.6 nM, with the highest selectivity versus PI3Kα (8.2 μM) and the lowest versus PI3Kγ and PI3Kβ (72 and 94 nM, respectively).
|Isoangustone A, a natural product isolated and purified from the roots of Licorice with antitumor activity, induces G1 cycle arrest in DU145 human prostate and 4T1 murine mammary cancer cells, dampens mesangial sclerosis associated with inflammation in response to high glucose through hindering TGF-β and NF-κB signaling, inhibits cell proliferation by targeting PI3K, MKK4, and MKK7 in human melanoma and shows strong ferric reducing activities and effectively scavenged DPPH, ABTS(+), and singlet oxygen radicals.
|IITZ-01 is an inhibitor of lysosomotropic autophagy It can enhance autophagosome accumulation and inhibit autophagosomal degradation that finally resulting in the inhibition of autophagy
|Hirsutenone, a natural product isolated and purified from the eaves of Alnus nepalensis, exhibits anti-cancer effect against prostate cancer through a direct physical inhibition of Akt1/2, attenuates adipogenesis by directly targeting PI3K and ERK during MCE in 3T3-L1 preadipocytes, underscoring the potential therapeutic application of Hirsutenone in preventing obesity, and may exert a preventive effect against microbial endotoxin lipopolysaccharide-induced inflammatory skin diseases through inhibition of ERK pathway-mediated NF-kappaB activation. Hirsutenone showed potent PL(pro) inhibitory activity with IC50 value of 4.1µM.
|GSK-2269557 has low oral bioavailability (F=2%) and in vivo clearance of 28 mL/min/kg but has a high volume of distribution of 6.3 L/kg.
|GDC-0032 is a potent, next-generation isoform-sparing PI3K inhibitor targeting PI3K with IC50 of 0.29 nM0.12 nM0.97nM, 10 fold selective over PI3K.
|Fimepinostat mesylate is a small molecule inhibitor of histone deacetylase and PI3 kinase.
|Dezapelisib is an orally bioavailable, selective inhibitor of the delta isoform of the 110 kDa catalytic subunit of class I phosphoinositide-3 kinases (PI3K).
|BGT226 is a phosphatidylinositol 3-kinase (PI3K) inhibitor with potential antineoplastic activity. PI3K inhibitor BGT226 specifically inhibits PIK3 in the PI3K/AKT kinase (or protein kinase B) signaling pathway, which may trigger the translocation of cytosolic Bax to the mitochondrial outer membrane, increasing mitochondrial membrane permeability; apoptotic cell death may ensue. Bax is a member of the proapoptotic Bcl2 family of proteins.
|BEZ235 tosylate is a dual PI3K and mTOR kinase inhibitor with IC50 values of 4, 75, 7, 5 nM for PI3K, , , , respectively.
|BEBT-908 is a PI3K inhibitor with an IC50 0.1 M, and also inhibits HDAC (0.1 M IC50 1 M) .
|BAY-1082439 is a highly selective PI3K 110α/β inhibitor. Upon binding to P-gp and BCRP, BAY-1082439 enhanced the ATPase activity of both P-gp and BCRP, implying the potential of BAY-1082439 to increase drug accumulation by blocking the efflux activity of both P-gp and BCRP.
|AMG 511 is a potent and orally available pan inhibitor of class I PI3Ks, with Kis of 4 nM, 6 nM, 2 nM and 1 nM for PI3Kα, β, δ and γ, respectively. AMG 511 significantly suppresses PI3K signaling that is indicated by p-Akt (Ser473) decrease. AMG 511 exhibits anti-tumor activity in mouse glioblastoma xenograft model .
|Acacetin shows inhibiton of the proliferation and induction apoptosis for cancer cells. It is a flavonoid purified from the bark of acacia farnesiana with anti-peroxidant, antiarthritic, and anti-inflammatory activities,
|3-Methyladenine is a selective PI3K inhibitor for Vps34 and PI3K with IC50 of 25 M and 60 M.
|1,3-O-Dicaffeoylquinic acid is a natural product isolated and purified from the herbs of Cynara scolymus L., which may activates PI3KAkt.