The PI3K/Akt/mTOR signaling pathways is crucial to many aspects of cell growth and survival, in physiological as well as in pathological conditions. PI3Ks constitute a lipid kinase family. Class I PI3Ks are heterodimers composed of a catalytic (CAT) subunit (i.e., p110) and an adaptor/regulatory subunit (i.e., p85), and can be further divided into two subclasses: subclass IA (PI3Kα, β, and δ), which is activated by receptors with protein tyrosine kinase activity, and subclass IB (PI3Kγ), which is activated by receptors coupled with G proteins. Akt kinases belong to the AGC kinase family, related to AMP/GMP kinases and protein kinase C. mTOR is a key protein evolutionarily conserved from yeast to man and is essential for life. The mTORC1 complex is made up of mTOR, Raptor, mLST8, and PRAS40, and the mTORC2 complex is composed of mTOR, Rictor, Sin1, and mLST8.

Upon ligand binding, phosphorylated tyrosine residing in activated RTKs will bind to p85, then release the catalytic subunit p110. Activated p110 phosphorylated the PIP2 into the second messenger PIP3, and this reaction can be reversed by the PI3K antagonist PTEN. PIP3 will recruit the downstream Akt to inner membranes and phosphorylates Akt on its serine/threonine kinase sites (Thr308 and Ser473). Activated Akt is involved in the downstream mTORC1 mediated response to biogenesis of protein and ribosome.

Many genes belonging to the PI3K/Akt pathway have been implicated in the pathophysiology of solid tumors and sensitivity/resistance to chemotherapy. More and more studies are now focusing on the translational relevance of targeting these pathways in cancer therapy.

References:
[1] Porta C, et al. Front Oncol. 2014 Apr 14;4:64.
[2] Follo MY, et al. Adv Biol Regul. 2015 Jan;57:10-6.
[3] Li X, et al. Oncotarget. 2016 May 31;7(22):33440-50.


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PI3K-IN-35

PI3K-IN-35 (Compound 6l) is a highly selective PI3K inhibitor with IC50 values of 13.98, 7.22 and 10.94 μM for PI3K-α、PI3K-β and PI3K-δ, respectively. PI3K-IN-35 arrests cell cycle at G2/M phase and induces apoptosis. PI3K-IN-35 can be used in leukemia research[1].

  • CAS Number: 2458163-99-8
  • MF: C25H23N7O2
  • MW: 453.50
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bempedoic Acid

ETC-1002 is an activator of hepatic AMP-activated protein kinase (AMPK).

  • CAS Number: 738606-46-7
  • MF: C19H36O5
  • MW: 344.48600
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI3Kγ inhibitor 2

PI3Kγ inhibitor 2 (Compound 16) is an orally bioavailable, CNS-penetrant, isoform selective PI3Kγ inhibitor with a Ki of 4 nM[1].

  • CAS Number: 1315538-79-4
  • MF: C20H18F3N5O3
  • MW: 433.38
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BAY-3827

BAY-3827 is a potent and selective AMPK inhibitor with IC50 values of 1.4 nM at low (10 µM ATP concentration) and 15 nM at high (2 mM ATP concentration). BAY-3827 shows over 500-fold selectivity for most of the 331 kinases. BAY-3827 prevents phosphorylation of acetyl-CoA carboxylase 1 and shows strongest anti-proliferative activity in androgen-dependent prostate cancer cell lines[1].

  • CAS Number: 2377576-35-5
  • MF: C27H25FN6O
  • MW: 468.53
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PS210

PS 210 is a potent, specific activator of PDK1 that target the PIF-binding pocket of PDK1, does not alter the activity of any of the 121 kinases (S6K, PKB/Akt or GSK3).

  • CAS Number: 1221962-86-2
  • MF: C19H15F3O5
  • MW: 380.319
  • Catalog: PDK-1
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L-Leucine-2-13C

L-Leucine-2-13C is the 13C-labeled L-Leucine. L-Leucine is an essential branched-chain amino acid (BCAA), which activates the mTOR signaling pathway[1].

  • CAS Number: 201612-66-0
  • MF: C513CH13NO2
  • MW: 132.16600
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: >300ºC(lit.)
  • Flash Point: N/A

Amdizalisib

Amdizalisib is a PI3K inhibitor and used for the research of inflammatory disease, autoimmune disease or cancer[1].

  • CAS Number: 1894229-05-0
  • MF: C19H15ClN8
  • MW: 390.83
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

24-Methylene cycloartanyl ferulate

24-Methylenecycloartanyl ferulate is a γ-oryzanol compound. 24-Methylenecycloartanyl ferulate promotes parvin-beta expression in human breast cancer cells. 24-Methylenecycloartanyl ferulate is a potential ATP-competitive Akt1 inhibitor (EC50= 33.3μM)[1].

  • CAS Number: 469-36-3
  • MF: C41H60O4
  • MW: 616.913
  • Catalog: Akt
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 668.4±40.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 193.5±20.8 °C

PI3K-IN-20

PI3K-IN-20 is a PI3k inhibitor extracted from WO2017101847 A1, compound 1[1].

  • CAS Number: 1845777-61-8
  • MF: C24H23ClFN5O5S
  • MW: 547.99
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MeBIO

MeBIO is a potent AhR (aryl hydrocarbon receptor) agonist, with IC50 of 44 μM (GSK-3) and 55 μM (CDK1/cyclin B), respectively. MeBIO is inactive on GSK-3β[1].

  • CAS Number: 667463-95-8
  • MF: C17H12BrN3O2
  • MW: 370.20
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(R)-PS210

(R)-PS210, the R enantiomer of PS210 (compound 4h-eutomer), is a substrate-selective allosteric activator of PDK1 with an AC50 value of 1.8 μM. (R)-PS210 targets to the PIF-binding pocket of PDK1. PIF: The protein kinase C-related kinase 2 (PRK2)-interacting fragment[1].

  • CAS Number: 1410101-89-1
  • MF: C19H15F3O5
  • MW: 380.31
  • Catalog: PDK-1
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI3Kβ-IN-1

PI3Kβ-IN-1 (compound (P)-14) is a selective and orally active PI3Kβ inhibitor, with an IC50 of 2 nM[1].

  • CAS Number: 2215098-77-2
  • MF: C25H14F2N8
  • MW: 464.43
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AKT-IN-13

AKT-IN-13 (compound 4b) is a potent Akt inhibitor with IC50s of 1.6 nM, 2.4 nM and 0.3 nM for Akt1, Akt2 and Akt3, respectively. AKT-IN-13 can be used for researching anticancer[1].

  • CAS Number: 2459489-51-9
  • MF: C24H31ClN6O2
  • MW: 470.99
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF 06409577

PF-06409577 is a potent and selective allosteric activator of AMPK α1β1γ1 isoform with an EC50 of 7 nM.

  • CAS Number: 1467057-23-3
  • MF: C19H16ClNO3
  • MW: 341.78800
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SRX3207

SRX3207 is an orally active and first-in-class dual Syk/PI3K inhibitor. SRX3207 possesses anti-tumor activity[1].

  • CAS Number: 2254693-15-5
  • MF: C29H29N7O3S
  • MW: 555.65
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sarmentosin

Sarmentosin is an activator of Nrf2. Sarmentosin inhibits mTOR signaling and induces autophagy-dependent apoptosis in human HCC cells[1].

  • CAS Number: 71933-54-5
  • MF: C11H17NO7
  • MW: 275.26
  • Catalog: Apoptosis
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 621.9±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 329.9±31.5 °C

(5Z)-2-amino-5-(3,4-dimethoxybenzylidene)-1,3-thiazol-4(5H)-one

GSK-3β inhibitor 10 (compound 14a) is a highly potent GSK-3β inhibitor with an IC50 value of 80.5 nM. GSK-3β inhibitor 10 can be used for researching Alzheimer’s disease[1].

  • CAS Number: 1198098-03-1
  • MF: C12H12N2O3S
  • MW: 264.300
  • Catalog: GSK-3
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 454.8±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 228.9±31.5 °C

API-1

API-1, a potent Akt/PKB inhibitor, binds to the PH domain and inhibits Akt membrane translocation. API-1 efficiently reduces the phosphorylation levels of Akt with an IC50 of ∼0.8 μM. API-1 is selective for PKB and does not inhibit the activation of PKC, and PKA. API-1 also induces apoptosis by synergizing with TNF-related apoptosis-inducing ligand (TRAIL)[1][2].

  • CAS Number: 36707-00-3
  • MF: C13H15N5O6
  • MW: 337.28800
  • Catalog: Apoptosis
  • Density: 1.792g/cm3
  • Boiling Point: 795.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 435.1ºC

Desmethyl VS-5584

Desmethyl-VS-5584 is a dimethyl analog of VS-5584 which is an potent and selective mTOR/PI3K dual inhibitor with pyrido [2,3-d] pyrimidine structure[1].

  • CAS Number: 1246535-95-4
  • MF: C16H20N8O
  • MW: 340.383
  • Catalog: mTOR
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 669.3±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 358.6±34.3 °C

GNF-4877

GNF4877 is a potent DYRK1A and GSK3β inhibitor with IC50s of 6 nM and 16 nM, respectively, which leads to blockade of nuclear factor of activated T-cells (NFATc) nuclear export and increased β-cell proliferation (EC50 of 0.66 μM for mouse β (R7T1) cells)[1].

  • CAS Number: 2041073-22-5
  • MF: C25H27FN6O4
  • MW: 494.52
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK2334470

GSK2334470 is a highly specific and potent inhibitor of PDK1 with an IC50 of 10 nM.

  • CAS Number: 1227911-45-6
  • MF: C25H34N8O
  • MW: 462.591
  • Catalog: PDK-1
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY294002

LY294002 is a broad-spectrum inhibitor of PI3K with IC50s of 0.5, 0.57, and 0.97 μM for PI3Kα, PI3Kδ and PI3Kβ, respectively. It also inhibits CK2 with an IC50 of 98 nM.

  • CAS Number: 154447-36-6
  • MF: C19H17NO3
  • MW: 307.343
  • Catalog: Autophagy
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 494.6±45.0 °C at 760 mmHg
  • Melting Point: 182-184ºC
  • Flash Point: 253.0±28.7 °C

AMPK activator 9

AMPK activator 9 (ZM-6) is a potent AMPK (α2β1γ1) activator with an EC50 value of 1.1 µM. AMPK activator 9 has the potential for the research of type 2 diabetes[1].

  • CAS Number: 1858204-23-5
  • MF: C31H28F4N4O4
  • MW: 596.57
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Methyllucidone

Methyllucidone is a neuroprotective agent and an antioxidant that can be isolated from Lindera erythrocarpa Makino. Methyllucidone inhibits the ROS production, and activates antioxidant signaling pathways that include Nrf-2 and PI3K[1].

  • CAS Number: 19956-54-8
  • MF: C16H14O4
  • MW: 270.280
  • Catalog: Keap1-Nrf2
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 514.0±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 231.0±30.2 °C

3α-Hydroxymogrol

3α-Hydroxymogrol is a triterpenoid isolated from Siraitia grosvenorii Swingle, acts as a potent AMPK activator, and enhances AMPK phosphorylation[1].

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Eudebeiolide B

Eudebeiolide B is a compound that can be isolated from Salvia plebeia R. Br. Eudebeiolide B inhibits osteoclastogenesis by regulating RANKL-induced NF-κB, c-Fos and calcium signaling. Eudebeiolide B can be used for osteoclast-related diseases research[1].

  • CAS Number: 1934299-51-0
  • MF: C15H18O4
  • MW: 262.30
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Larixol

Larixol is an fMLP inhibitor and also inhibits Src kinase, ERK1/2, p38 and AKT phosphorylation signals in immune regulation. Larixol can interfere with the interaction between the βγ subunit of the fMLP receptor Gi protein and its downstream molecules, thereby inhibiting fMLP-induced respiratory burst. Larixol inhibits fMLP (0.1 μM)-induced superoxide anion production (IC50: 1.98 μM), cathepsin G release (IC50: 2.76 μM), and chemotaxis. Larixol improves neutrophil hyperactivation and reduces inflammation or tissue damage. A series of Larixol derivatives were found to have inhibitory effects on FSGS-related TRPC6 functional mutants[1][2].

  • CAS Number: 1438-66-0
  • MF: C24H38O4
  • MW: 390.55600
  • Catalog: ERK
  • Density: 1.01g/cm3
  • Boiling Point: 440.5ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 205.3ºC

FD274

FD274 is a highly potent PI3K/mTOR dual inhibitor with IC50s of 0.65 nM, 1.57 nM, 0.65 nM, 0.42 nM, and 2.03 nM against PI3Kα/β/γ/δ and mTOR, respectively. FD274 exhibits significant anti-proliferation of AML cell lines (HL-60 and MOLM-16). FD274 demonstrates dose-dependent inhibition of tumor growth in the HL-60 xenograft model. FD274 has the potential for acute myeloid leukemia research[1].

  • CAS Number: 2641899-38-7
  • MF: C22H14ClFN6O2S
  • MW: 480.90
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ABC 1183

ABC1183 is a potent, selective, orally active GSK3α/β and CDK9 inhibitor with IC50 of 327/657 nM and 321 nM (CDK9/cyclin T1), shows growth inhibitory activity against a broad panel of cancer cell lines; decreases cell survival through G2/M arrest and modulates oncogenic signaling through changes in GSK3, GS and β-catenin phosphorylation and MCL1 expression; suppresses tumor growth and inflammation-driven gastrointestinal disease symptoms without organ or hematological toxicity in vivo.

  • CAS Number: 1042735-18-1
  • MF: C18H14N4OS
  • MW: 334.397
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3,7,7-Trimethyl-4-(pyridin-3-yl)-2,4,6,7,8,9-hexahydro-5H-pyrazolo[3,4-b]quinolin-5-one

GSK3-IN-4 (compound 0715) is a potent GSK3 inhibitor. GSK3-IN-4 can be used for psychiatric disorder research[1].

  • CAS Number: 748145-19-9
  • MF: C18H20N4O
  • MW: 308.38
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A