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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α-Linolenic acid-13C18

α-Linolenic acid-13C18 is the 13C labeled α-Linolenic acid. α-Linolenic acid, isolated from seed oils, is an essential fatty acid that cannot be synthesized by humans. α-Linolenic acid can affect the process of thrombotic through the modulation of PI3K/Akt signaling. α-Linolenic acid possess the anti-arrhythmic properties and is related to cardiovascular disease and cancer[1].

  • CAS Number: 287111-28-8
  • MF: 13C18H30O2
  • MW: 296.29700
  • Catalog: Akt
  • Density: 0.971 g/mLat 25 °C
  • Boiling Point: N/A
  • Melting Point: -11 °C
  • Flash Point: 113 °C

S14161

Pichromene (S14161) is an anticancer agent and weak PI3K inhibitor. Pichromene can effectively inhibit tumor growth in leukemia mouse models and can be used in cancer research[1][2].

  • CAS Number: 883046-50-2
  • MF: C17H14FNO4
  • MW: 315.30
  • Catalog: PI3K
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 456.2±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 229.7±28.7 °C

EX-229

EX229, a Benzimidazole derivative, is a potent and allosteric activator of AMP-activated protein kinase (AMPK), with Kds of 0.06 μM, 0.06 μM and 0.51 μM for α1β1γ1, α2β1γ1 and α1β2γ1 in biolayer interferometry, respectively.

  • CAS Number: 1219739-36-2
  • MF: C24H18ClN3O3
  • MW: 431.87
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CGK 733

CGK733 is a potent ATM/ATR inhibitor, used for the research of cancer.

  • CAS Number: 905973-89-9
  • MF: C23H18Cl3FN4O3S
  • MW: 555.836
  • Catalog: ATM/ATR
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Torin 2

Torin 2 is an mTOR inhibitor with EC50 of 0.25 nM for inhibiting cellular mTOR activity, and exhibits 800-fold selectivity over PI3K (EC50: 200 nM). Torin 2 also inhibits DNA-PK with an IC50 of 0.5 nM in the cell free assay. Torin 2 can suppress both mTORC1 and mTORC2.

  • CAS Number: 1223001-51-1
  • MF: C24H15F3N4O
  • MW: 432.397
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 623.7±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 331.0±31.5 °C

PI4KA inhibitor-F1

GSK-F1 (Compound F1) is an orally active PI4KA inhibitor with pIC50 values of 8.0, 5.9, 5.8, 5.9, 5.9 and 6.4 against PI4KA, PI4KB, PI3KA, PI3KB, PI3KG and PI3KD, respectively. GSK-F1 can be used for HCV infection research[1].

  • CAS Number: 1402345-92-9
  • MF: C27H18F5N5O4S
  • MW: 603.52
  • Catalog: PI3K
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 744.3±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 404.0±35.7 °C

SF1670

SF1670 is a potent and specific phosphatase and tensin homolog deleted on chromosome 10 (PTEN) inhibitor.

  • CAS Number: 345630-40-2
  • MF: C19H17NO3
  • MW: 307.343
  • Catalog: Phosphatase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 554.1±29.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 208.0±24.4 °C

Amde-1

AMDE-1 is a potent autophagy inducer. AMDE-1 induces autophagy by the AMPK-mTORC1-ULK1 pathway and at the same time inhibited autophagy-mediated degradation by causing lysosome dysfunction. AMDE-1 can be used in research of cancer[1].

  • CAS Number: 478043-30-0
  • MF: C18H8ClF6N3
  • MW: 415.72
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TAS0612

TAS0612 is an orally novel inhibitor of RSK、AKT and S6K. TAS0612 has broad-spectrum activity against tumor models via inhibiting cell growth[1].

  • CAS Number: 2148902-58-1
  • MF: C27H34F3N9O2
  • MW: 573.61
  • Catalog: Ribosomal S6 Kinase (RSK)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK690693

GSK-690693 is a pan-Akt inhibitor targeting Akt1/2/3 with IC50 of 2/13/9 nM in cell-free assays, also sensitive to the AGC kinase family: PKA, PrkX and PKC isozymes. 

  • CAS Number: 937174-76-0
  • MF: C21H27N7O3
  • MW: 425.484
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 683.8±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 367.3±34.3 °C

TAS-117

TAS-117 is a highly selective, non-ATP competitive pan-Akt inhibitor with IC50 of 4.8/1.6/44 nM for Akt1/Akt2/Akt3 respectively; shows minimal inhibitory activities against others kinases including PI3K, PDK1, and mTOR; inhibits Akt kinase activity but not p-Akt, blocks basal phosphorylation of Akt and downstream p-FKHR/FKHRL1; induces significant cytotoxicity in MM cells associated with inhibition of IL6 secretion; triggers apoptosis and autophagy, induces ER stress response, inhibits human MM cell growth in murine xenograft models. Solid Tumors Phase 1 Clinical

  • CAS Number: 1402602-94-1
  • MF: C26H24N4O2
  • MW: 424.494
  • Catalog: Apoptosis
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 655.8±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 350.4±34.3 °C

ARN25068

ARN25068 is a sub-micromolar inhibitor of the three protein kinases, GSK-3β, FYN and DYRK1A to tackle tau hyperphosphorylation[1].

  • CAS Number: 2649882-80-2
  • MF: C19H18N6S
  • MW: 362.45
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TCS 2002

GSK-3β inhibitor 9 (Compound 9b) is a highly selective, orally bioavailable and potent GSK-3β inhibitor with the IC50 of 35 nM. GSK-3β inhibitor 9 shows good pharmacokinetic profiles including favorable BBB penetration. GSK-3β inhibitor 9 can be used for the research of Alzheimer’s disease[1].

  • CAS Number: 1005201-24-0
  • MF: C18H14N2O3S
  • MW: 338.38000
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK3 Inhibitor XIII

GSK-3 Inhibitor XIII is a potent and ATP-competitive GSK-3 inhibitor with a Ki of 24 nM[1][1][2].

  • CAS Number: 404828-08-6
  • MF: C18H15N5
  • MW: 301.34500
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FD2056

FD2056 is a potent and orally active PI3K inhibitor. FD2056 inhibits PI3Kα/PI3Kβ/PI3Kγ/PI3Kδ with IC50s of 0.30, 0.80, 1.10, 0.42 nM. FD2056 also inhibits CDK2-CyclinA2 and CDK4-CyclinD3 with IC50 of 115.95 and 2782.15 nM. FD2056 inhibits breast cancer cell proliferation with IC50s of 1.06, 0.04, 1.40 μM for MDA-MB-231, MDA-MB-468, MCF-7 cells. FD2056 also induces cancer apoptosis and inhibits tumor growth[1].

  • CAS Number: 2685870-87-3
  • MF: C23H17ClN6O2S
  • MW: 476.94
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CCT 365623 hydrochloride

CCT 365623 (CCT365623) hydrochloride is a potent, orally active small molecule inhibitor of lysyl oxidase (LOX) with IC50 of 0.89 uM; inhibits LOX actvity in living cell system (MDCK cysts) at 5 uM, reduces EGFR retention at the cell surface, suppresses EGFR and AKT phosphorylation driven by EGF, also activates SMAD2 and downregulates MATN2; delays the growth of primary and metastatic tumour cells in vivo.

  • CAS Number: 2126136-98-7
  • MF: C18H18ClNO4S3
  • MW: 443.975
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Chrysomycin A

Chrysomycin A (Chr-A), an antibiotic, can be obtained from Streptomyces. Chrysomycin A exhibits antitumor and anti-tuberculous and MRSA activities. As for glioblastoma, Chrysomycin A inhibits the proliferation, migration, and invasion of cancer cells through the Akt/GSK-3β/β-catenin signaling pathway[1].

  • CAS Number: 82196-88-1
  • MF: C28H28O9
  • MW: 508.517
  • Catalog: Bacterial
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 799.7±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 269.6±26.4 °C

MEK/PI3K-IN-2

MEK/PI3K-IN-2 (compound 6s) is a potent MEK/PI3K inhibitor, with IC50 values of 352 nM (MEK1), 107 nM (PI3Kα), and 137 nM (PI3Kδ), respectively. MEK/PI3K-IN-2 suppresses pAKT and pERK1/2 levels. MEK/PI3K-IN-2 shows anti-proliferative activity against tumor cell lines[1].

  • CAS Number: 2281803-33-4
  • MF: C38H41F5IN9O7
  • MW: 957.68
  • Catalog: PERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MCX 28

MCX 28, a triple PI3K/mTOR/PIM inhibitor, displays low nanomolar activity.

  • CAS Number: 1414453-58-9
  • MF: C25H19N5O4S3
  • MW: 549.64
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Akt Inhibitor IV

Akt inhibitor-IV (AKTIV) acts as a PI3K-Akt inhibitor at the E isomer (HY-14971), with potent cytotoxicity[1].

  • CAS Number: 681281-88-9
  • MF: C31H27IN4S
  • MW: 614.54
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

D-α-Hydroxyglutaric acid

D-α-Hydroxyglutaric acid ((R)-2-Hydroxypentanedioic acid) is the principal metabolite accumulating in neurometabolic disease D-2-hydroxyglutaric aciduria. D-α-Hydroxyglutaric acid is a weak competitive antagonist of α-ketoglutarate (α-KG) and inhibits multiple α-KG-dependent dioxygenases with a Ki of 10.87 mM. D-α-Hydroxyglutaric acid increases reactive oxygen species (ROS) production. D-α-Hydroxyglutaric acid binds and inhibits ATP synthase and inhibits mTOR signaling[1][2][3][4][5].

  • CAS Number: 13095-47-1
  • MF: C5H8O5
  • MW: 148.11400
  • Catalog: ATP Synthase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

12-Hydroxyabieta-8,12-diene-11,14-dione

Royleanone, a diterpenoid isolated from plants, inhibits the proliferation of cancer cells by inducing cell cycle arrest and mitochondria-mediated apoptosis, also inhibits cell migration potential, inhibits mTOR/PI3/AKT signaling pathway in LNCaP prostate cancer cells[1].

  • CAS Number: 6812-87-9
  • MF: C20H28O3
  • MW: 316.43
  • Catalog: Akt
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 426.4±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 225.8±25.2 °C

Aschantin

Aschantin, a bisepoxylignan, can be isolated from Magnolia biondii. Aschantin has antiplasmodial, Ca2+-antagonistic, platelet activating factor-antagonistic, and chemopreventive activities. Aschantin is a mTOR kinase inhibitor. Aschantin is also an inhibitor of Cytochrome P450 and UGT enzyme[1][2].

  • CAS Number: 13060-15-6
  • MF: C22H24O7
  • MW: 400.42
  • Catalog: Cytochrome P450
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 525.8±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 214.7±30.0 °C

Akt-I-1,2 HCl

AKT-IN-20 is an AKT inhibitor, and can be used for research of cancer[1]

  • CAS Number: 473382-50-2
  • MF: C23H22ClN3
  • MW: 375.89400
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI3Kα-IN-13

PI3Kα-IN-13 (Compound 18a) is a PI3Kα inhibitor (IC50: 2.5 nM). PI3Kα-IN-13 induces tumor cell apoptosis. PI3Kα-IN-13 inhibits cancer cell proliferation with IC50s of 0.75 μM (MCF-7), 3.79 μM (HCT-116), 13.71 μM (MDA-MB-231), 9.85 μM (SW620), respectively. PI3Kα-IN-13 inhibits tumor cell colony formation, migration and invasion[1].

  • CAS Number: 2955529-67-4
  • MF: C21H19N5O3
  • MW: 389.41
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

rac-AZD 6482

rac-AZD 6482 (rac-KIN-193) is a less active racemate of AZD 6482. AZD 6482 is a potent and selective p110β inhibitor with an IC50 of 0.69 nM.

  • CAS Number: 663620-70-0
  • MF: C22H24N4O4
  • MW: 408.45000
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY2090314

LY2090314 is a potent inhibitor of glycogen synthase kinase-3 (GSK-3) with IC50 values of 1.5 nM and 0.9 nM for GSK-3α and GSK-3β, respectively.

  • CAS Number: 603288-22-8
  • MF: C28H25FN6O3
  • MW: 512.535
  • Catalog: GSK-3
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(2α,3β)-2,3-Dihydroxylup-20(29)-en-28-oic acid

Alphitolic acid (Aophitolic acid) is an anti-inflammatory triterpene could found in quercus aliena. Alphitolic acid blocks Akt–NF-κB signaling to induce apoptosis. Alphitolic acid induces autophagy. Alphitolic acid has anti-inflammatory activity and down-regulates the NO and TNF-α production. Alphitolic acid can be used for cancer and inflammation research[1][2][3].

  • CAS Number: 19533-92-7
  • MF: C30H48O4
  • MW: 472.700
  • Catalog: Apoptosis
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 566.4±30.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 310.4±21.1 °C

L-Leucine-2-13C,15N

L-Leucine-2-13C,15N is the 13C- and 15N-labeled L-Leucine. L-Leucine is an essential branched-chain amino acid (BCAA), which activates the mTOR signaling pathway[1].

  • CAS Number: 285977-88-0
  • MF: C513CH1315NO2
  • MW: 133.16
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3-(pyridin-2-ylmethylidene)-1H-indol-2-one

(E/Z)-GSK-3β inhibitor 1 is a racemic compound of (E)-GSK-3β inhibitor 1 and (Z)-GSK-3β inhibitor 1 isomers. GSK-3β inhibitor 1 (compound 3a) is a glycogen synthase kinase 3β (GSK-3β) inhibitor and demonstrates high antidiabetic efficacy, with an IC50 of 4.9 nM[1].

  • CAS Number: 3367-88-2
  • MF: C14H10N2O
  • MW: 222.24200
  • Catalog: GSK-3
  • Density: 1.291g/cm3
  • Boiling Point: 457.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 230.3ºC