pi3k in 6

PI3K-IN-6 is an oral active and highly selective inhibitor of phosphoinositide 3-kinase (PI3K) β/δ(IC50 values of 7.8 nM/5.3 nM , respectively).

PI3K/Akt/mTOR-IN-6 (Compound JW4) is an orally active inhibitor of the PI3K/Akt/mTOR pathway. It induces apoptosis through the mitochondrial pathway and demonstrates significant anti-non-small cell lung cancer activity.

PI3K/mTOR Inhibitor-6 (Compound 19c) is a potent dual PI3K/mTOR inhibitor, exhibiting greater stability than gedatolisib in artificial gastric fluid. At 10 μM, PI3K/mTOR Inhibitor-6 significantly inhibits the PI3K/Akt/mTOR signaling pathway and has shown potential for cancer research.

PI3Kδ/HDAC6-IN-1 (Compound 22E) is an orally active dual inhibitor of PI3Kδ and HDAC6, with IC50 values of 2.4 nM and 6.2 nM, respectively. It exhibits potent antiproliferative effects against non-Hodgkin's lymphoma (NHL) cells and demonstrates antitumor activity in vivo without significant toxicity. PI3Kδ/HDAC6-IN-1 induces cell cycle arrest at the G0/G1 phase and triggers apoptosis. Additionally, it inhibits the PI3K/AKT/mTOR signaling pathway and enhances the acetylation levels of α-tubulin and histone H3.

PI3Kα-IN-6 (Compound 5b) is a PI3Kα inhibitor that demonstrates anticancer properties without harming normal cells, by increasing ROS production, decreasing mitochondrial membrane potential, and inducing apoptosis.

PI3Kγ Inhibitor 6, a specific inhibitor of PI3Kγ, is utilized in the study of inflammatory and autoimmune diseases.

PI3Kα/HDAC6-IN-1 (compound 21j) is a dual inhibitor of PI3Kα and HDAC6, with IC50 values of 2.9 nM and 26 nM, respectively. It hinders AKT(Ser473) phosphorylation and promotes the accumulation of acetylated α-tubulin without affecting acetylated histones H3 and H4. The compound exhibits potent anti-cancer efficacy, inhibiting the L-363 cell line with an IC50 of 0.17 μM [1].

PI3K-IN-60 (Compound 34) is a selective PI3Kγ inhibitor for studying autoimmune diseases and cancers such as multiple sclerosis, breast cancer, and pancreatic ductal adenocarcinoma.

4-Vinylcyclohexene Dioxide (VCD) is an industrial epoxy resin intermediate and metabolite that exhibits a highly selective destructive effect on oocytes in primordial and primary follicles; it is used as a key inducer for establishing animal models of premature ovarian failure and premenopause. 4-Vinylcyclohexene Dioxide exerts its ovarian toxicity by activating caspase-dependent apoptotic pathways and can induce apoptosis in ovarian granulosa cells by upregulating reactive oxygen species and activating the PI3K/Akt/mTOR signaling pathway. It is used in reproductive toxicology and endocrine regulation research.

Luteolin-7-rutinoside is a natural product that alleviates LPS-induced acute liver injury by inhibiting the PI3K/AKT/AMPK/NF-κB signaling pathways and suppressing TNF-α, IL-6, and IL-1β.

Rhodiolin, a natural product from Rhodiola rosea, blocks glycolysis of glucose 6-phosphate isomerase (GPI) in human papillary thyroid cancer (PTC), inhibits phosphorylation of the PI3K/AKT/mTOR signaling pathway and induces apoptosis of PTC cells.

AMG 511 is a potent and orally available pan inhibitor of class I PI3Ks (Kis of 4 nM, 6 nM, 2 nM, and 1 nM for PI3Kα, β, δ, and γ, respectively), exhibiting anti-tumor activity in a mouse glioblastoma xenograft model[1]. AMG 511 significantly suppresses PI3K signaling as indicated by a decrease in p-Akt (Ser473).

Dehydroxy-oridonin-vinyl ester (Compound 6k) is an anticancer agent. It exhibits exceptionally potent antiproliferative activity against SU-DHL-6 cells, with an IC₅₀ value of 0.12 μM. Dehydroxy-oridonin-vinyl ester induces apoptosis by inhibiting the activation of the PI3K/Akt signaling pathway, without affecting cell cycle progression. Dehydroxy-oridonin-vinyl is applicable in lymphoma research.

TBK1/IKKε-IN-4, a 6-aminopyrazolopyrimidine derivative, serves as a potent, selective inhibitor for TBK1 and IKKε, demonstrating IC50 values of 13 nM and 59 nM, respectively. This compound exhibits significantly reduced activity, by 100- to 1000-fold, against other protein kinases, such as PDK1, PI3K family members, and mTOR[1].

PI3K-IN-26 is an effective PI3K inhibitor. PI3K-IN-26 inhibits the proliferation of SU-DHL-6 cells, IC50= 36 nM.

HDAC-IN-43 is a potent HDAC 1/3/6 inhibitor with IC50 values of 82 nM for HDAC 1, 45 nM for HDAC 3, and 24 nM for HDAC 6, and a weak PI3K/mTOR inhibitor with IC50 values of 3.6 μM for PI3K and 3.7 μM for mTOR, exhibiting a broad-spectrum anti-proliferative effect.

PI3K-IN-37 (Example 84.1) is an inhibitor of PI3K α (IC50: 6 nM), PI3K β (IC50: 8 nM), and PI3K δ (IC50: 4 nM), and also inhibits mTOR with an IC50 of 4 nM.

1. Oroxylin A (Baicalein 6-methyl ether) has various anti-tumor effects including apoptosis, cell cycle arrest, drug-resistant reversion. 2. Oroxylin A possesses abilities of inhibiting the ATRA-induced IL-6 production via modulation of LAP/LIP/CHOP in leukemia cell lines, which could providing a therapeutic strategy for RAS. 3. Oroxylin A inhibits UCP2s triggers the MPTP opening, and promotes the apoptosis in CaCo-2 cells; uncoupling protein 2 plays a key role in mitochondrial apoptotic pathway. 4. Oroxylin A inhibits N1ICD translocating to the nucleus and binding to epithelial-mesenchymal transition-related transcription factor Snail, thus suppressing the invasion and migration of MCF-7 cells. 5. Oroxylin A improves the sensitivity of K562/ADM cells by increasing apoptosis in leukemic cells and decreasing the expression of CXCR4 and PI3K/Akt/NF-κB pathway, and probably served as a most promising agent for CML treatment.

1. 6-Shogaol (6-Shogaol) has antipyretic and analgesic effects in addition to inhibitory effect on lipoxygenase activity. 2. 6-shogaol has anti-inflammatory property, reduces the inflammatory response and protected the femoral cartilage from damage produced in a CFA monoarthritic model of the knee joint of rats. 3. 6-Shogaol inhibits the growth of human cancer cells and induces apoptosis in COLO 25 cells through modulation of mitochondrial functions regulated by reactive oxygen species (ROS). 4. 6-Shogaol effectively inhibit invasion and metastasis of hepatocellular carcinoma through diverse molecular mechanisms, including inhibition of the MAPK and PI3k/Akt pathways and NF-κB and STAT3 activities to suppress expression of MMP-2/-9 and uPA and block angiogenesis, could further regulate urokinase-type plasminogen activity.

6-O-Isobutyrylbritannilactone is a natural sesquiterpene and melanogenesis inhibitor capable of suppressing IBMX-induced melanogenesis in B16F10 cells. It modulates ERK, CREB, and PI3K/AKT pathways while reducing pigmentation in zebrafish embryos.

PI3Kδ-IN-17 (Compound S5) is a potent PI3K δ inhibitor with an IC50 value of 2.82 nM, significantly inhibiting SU-DHL-6 cell proliferation with an IC50 of 0.035 μM [1].

Anticancer agent 109 (compound 6-15) acts as an inhibitor targeting the Gas6-Axl axis, demonstrating significant anti-cancer properties. This compound suppresses the expression of Gas6, Axl, p-PI3K, and p-AKT in cancer cells, thereby inducing G1 phase arrest and promoting apoptosis of cancer cells. Additionally, Anticancer agent 109 effectively inhibits tumor growth in nude mouse tumor-bearing models [1].

Compound 19, also known as Antidiabetic agent 6, is an antidiabetic compound. It stimulates the translocation of GLUT4 by activating the PI3K/AKT-dependent signaling pathway. Furthermore, this compound reduces blood glucose levels in diabetic rats induced by streptozotocin.

Citronellol-d3 ((±)-Citronelloll-d3) is the deuterium-labeled form of Citronellol. Citronellol ((±)-Citronellol) acts as an orally effective apoptosis inducer. It can prevent oxidative stress, mitochondrial dysfunction, and apoptosis in the Parkinson's disease model of SH-SY5Y cells induced by 6-OHDA through the regulation of ROS-NO, MAPK/ERK, and PI3K/Akt signaling pathways. Additionally, Citronellol induces necroptosis in human lung cancer cells via the TNF-α pathway and reactive oxygen species (ROS) accumulation. It modulates the autophagy pathway by reducing LC-3 and p62 levels, inhibiting oxidative stress and neuroinflammation, thus offering neuroprotective effects in rat models of Parkinson's disease. Furthermore, Citronellol exhibits antifungal activity against Trichophyton rubrum by inhibiting ergosterol synthesis.