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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AMPK activator 10

AMPK activator 10 is an orally active, potent AMPK activator with EC150 of 44.3 nM by cell-ELISA. AMPK activator 10 increases the phosphorylation levels of ACC. AMPK activator 10 exhibits a glucose lowering effect[1].

  • CAS Number: 1914176-03-6
  • MF: C24H26ClFN4O6
  • MW: 520.94
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AMPK activator 2

AMPK activator 2 (compound 7a), a fluorine-containing proguanil derivative, up-regulates AMPK signal pathway and downregulates mTOR/4EBP1/p70S6K. AMPK activator 2 inhibits proliferation and migration of human cancer cell lines (UMUC3, T24, A549)[1].

  • CAS Number: 2410961-69-0
  • MF: C13H18F3N5
  • MW: 301.31
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Crebanine

Crebanine, an alkaloid from Stephania venosa, induces G1 arrest and apoptosis in human cancer cells. Crebanine exhibits anti-inflammatory activity via suppressing MAPKs and Akt signaling. Crebanine also possesses antiarrhythmic effect[1][2].

  • CAS Number: 25127-29-1
  • MF: C20H21NO4
  • MW: 339.385
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 488.2±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 145.4±25.9 °C

TCL1(10-24)

TCL1(10-24) is a encompassing the betaA strand of human TCL1. TCL1(10-24) is a Akt inhibitor. TCL1(10-24) interacts with the Akt PH domain prevented phosphoinositide binding and hence inhibits membrane translocation and activation of Akt. TCL1(10-24) inhibits cellular proliferation and anti-apoptosis. TCL1(10-24) has tumor growth in vivo[1].

  • CAS Number: 835655-37-3
  • MF: C88H123N23O23
  • MW: 1871.06
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dactolisib (BEZ235)

BEZ235 is a dual pan-class I PI3K and mTOR kinase inhibitor with IC50s of 4 nM/5 nM/7 nM/75 nM, and 20.7 nM for p110α/p110γ/p110δ/p110β and mTOR, respectively. BEZ235 inhibits both mTORC1 and mTORC2.

  • CAS Number: 915019-65-7
  • MF: C30H23N5O
  • MW: 469.54
  • Catalog: Autophagy
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 701.0±70.0 °C at 760 mmHg
  • Melting Point: 288-289°C
  • Flash Point: 377.8±35.7 °C

Xanthoangelol

Xanthoangelol, extracted from Angelica keiskei, suppresses obesity-induced inflammatory responses. Xanthoangelol possesses antibacterial activity[1][2]. Xanthoangelol and inhibits monoamine oxidases[3]. Xanthoangelol induces apoptosis in neuroblastoma and leukemia cells[4].

  • CAS Number: 62949-76-2
  • MF: C25H28O4
  • MW: 392.48700
  • Catalog: Bacterial
  • Density: 1.165g/cm3
  • Boiling Point: 605.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 334.2ºC

Usnic acid

(+)-Usnic acid is isolated from isolated from lichens, binds at the ATP-binding pocket of mTOR, and inhibits mTORC1/2 activity. (+)-Usnic acid inhibits the phosphorylation of mTOR downstream effectors: Akt (Ser473), 4EBP1, S6K, induces autophay, with anti-cancer activity[1].

  • CAS Number: 7562-61-0
  • MF: C18H16O7
  • MW: 344.315
  • Catalog: mTOR
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 638.2±55.0 °C at 760 mmHg
  • Melting Point: 201-203 °C(lit.)
  • Flash Point: 236.0±25.0 °C

(E/Z)-BIO-acetoxime

(E/Z)-BIO-acetoxime (GSK-3 Inhibitor X) is a potent and selective GSK-3α/β inhibitor, with an IC50 of 10 nM. (E/Z)-BIO-acetoxime shows more than 200-flod selectivity over CDK5/p25, CDK2/cyclin A and CDK1/cyclin B (IC50=2.4, 4.3, 63 μM)[1].

  • CAS Number: 740841-15-0
  • MF: C18H12BrN3O3
  • MW: 398.21000
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Chonglou Saponin VII

Paris saponin VII (Chonglou Saponin VII) is a steroidal saponin isolated from the roots and rhizomes of Trillium tschonoskii Maxim. Paris saponin VII-induced apoptosis in K562/ADR cells is associated with Akt/MAPK and the inhibition of P-gp. Paris saponin VII attenuates mitochondrial membrane potential, increases the expression of apoptosis-related proteins, such as Bax and cytochrome c, and decreases the protein expression levels of Bcl-2, caspase-9, caspase-3, PARP-1, and p-Akt. Paris saponin VII induces a robust autophagy in K562/ADR cells and provides a biochemical basis in the treatment of leukemia[1].

  • CAS Number: 68124-04-9
  • MF: C51H82O21
  • MW: 1031.184
  • Catalog: Bcl-2 Family
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ALK-IN-26

ALK-IN-26 is an ALK inhibitor with IC50 value of 7.0 μM for ALK tyrosine kinase. ALK-IN-26 has good pharmacokinetic properties and blood-brain barrier (BBB) permeability. ALK-IN-26 can induce apoptosis, autophagy and necrosis. ALK-IN-26 can be used in glioblastoma studies[1].

  • CAS Number: 2447607-85-2
  • MF: C24H23NO3S
  • MW: 405.51
  • Catalog: Caspase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(Rac)-Nedisertib

Rac-Nedisertib (Rac-M3814) is a racemate of Nedisertib, a potent DNA-PK inhibitor, with an IC50 of <3 nM[1].

  • CAS Number: 1637542-34-7
  • MF: C24H21ClFN5O3
  • MW: 481.91
  • Catalog: DNA-PK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PIK-inhibitors

PI3K-IN-32 (compound 35) is a potent PI3K p110α inhibitor with an pIC50 of 6.85[1].

  • CAS Number: 371934-59-7
  • MF: C19H17N5O2
  • MW: 347.371
  • Catalog: PI3K
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 526.1±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 272.0±30.1 °C

PI3Kα-IN-6

PI3Kα-IN-6 (Compound 5b) is a PI3Kα inhibitor. PI3Kα-IN-6 exhibits anticancer potential and no toxicity in normal cells. PI3Kα-IN-6 increases generation of ROS, reduces mitochondrial membrane potential (MMP) and induces apoptosis[1].

  • CAS Number: 2272894-14-9
  • MF: C16H15IN2OS
  • MW: 410.27
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CC214-1

CC214-1 is a potentially efficacious mTOR inhibitor that induces autophagy [1],with an IC50 is 0.002 μM. CC214-1 proved to be useful as an in vitro tool compound for the exploration of mTOR kinase biology. CC214-1 can be used for Glioblastoma study[2].

  • CAS Number: 1021920-32-0
  • MF: C20H21N7O2
  • MW: 391.43
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CCT128930 hydrochloride

CCT128930 hydrochloride is a potent and selective inhibitor of AKT (IC50=6 nM). CCT128930 hydrochloride has 28-fold selectivity over the closely related PKA kinase (IC50=168 nM) through the targeting of Met282 of AKT (Met173 of PKA-AKT chimera), as well as 20-fold selectivity over p70S6K (IC50=120 nM). CCT128930 hydrochloride induces cell cycle arrest, DNA damage, and autophagy. Antitumor activity[1][2].

  • CAS Number: 2453324-32-6
  • MF: C18H21Cl2N5
  • MW: 378.30
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L-Leucine-13C6,15N

L-Leucine-13C6,15N 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: 202406-52-8
  • MF: 13C6H1315NO2
  • MW: 138.122
  • Catalog: mTOR
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI-273

PI-273 is a first reversibly and specific phosphatidylinositol 4-kinase (PI4KIIα) inhibitor with an IC50 of 0.47 μM. PI-273 can inhibit breast cancer cell proliferation, block the cell cycle and induce cell apoptosis[1].

  • CAS Number: 925069-34-7
  • MF: C16H16ClN3O2S2
  • MW: 381.90
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

M3814

M3814 is a potent and selective inhibitor of DNA-dependent Protein Kinase (DNA-PK).

  • CAS Number: 1637542-33-6
  • MF: C24H21ClFN5O3
  • MW: 481.91
  • Catalog: DNA-PK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(24E)-3,7-Dioxolanosta-8,24-dien-26-oic acid

Ganoderic acid DM, a natural triterpenoid isolated from Ganoderma lucidum, induces DNA damage, G1 cell cycle arrest and apoptosis in human breast cancer cells. Ganoderic acid DM as a specific inhibitor of osteoclastogenesis[1][2].

  • CAS Number: 173075-45-1
  • MF: C30H44O4
  • MW: 468.668
  • Catalog: Apoptosis
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 602.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 332.0±28.0 °C

OSU-03012 (AR-12)

OSU-03012 is a PDK-1 inhibitor with an IC50 of 5 μM.

  • CAS Number: 742112-33-0
  • MF: C26H19F3N4O
  • MW: 460.451
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 683.0±55.0 °C at 760 mmHg
  • Melting Point: 177-180 °C
  • Flash Point: 366.9±31.5 °C

BF 738735

BF738735 is a phosphatidylinositol 4-kinase III beta (PI4KIIIβ) inhibitor with an IC50 of 5.7 nM.

  • CAS Number: 1436383-95-7
  • MF: C21H19FN4O3S
  • MW: 426.464
  • Catalog: PI4K
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

M4076

M4076 is a higly potent, selective, ATP-competitive inhibitor of ATM kinase with IC50 of 0.2 nM.M4076 sensitizes tumor cell lines to radiation therapy in vitro and strongly enhances the anti-tumor activity of ionizing radiation in vivo.

  • CAS Number: 2020089-41-0
  • MF: C23H21FN6O3
  • MW: 448.458
  • Catalog: ATM/ATR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(R)-Nedisertib

(R)-Nedisertib ((R)-M3814) is a less active R-enantiomer of Nedisertib, with an IC50 in the range of 7-30 nM for DNA-PK[1].

  • CAS Number: 1637542-32-5
  • MF: C24H21ClFN5O3
  • MW: 481.91
  • Catalog: DNA-PK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Charantin

Charantin is a steroidal saponin isolated from Momordica charantia, and has insulin-like activity, by increasing the release of insulin and slowing down gluconeogenesis. Charantin can against GSK-3[1].

  • CAS Number: 57126-62-2
  • MF: C105H178O18
  • MW: 822.92
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 266-268℃
  • Flash Point: N/A

Afzelin

Afzelin (Kaempferol-3-O-rhamnoside) is is a flavonol glycoside found in Houttuynia cordata Thunberg and is widely used in the preparation of antibacterial and antipyretic agents, detoxicants and for the treatment of inflammation. Afzelin attenuates the mitochondrial damage, enhances mitochondrial biogenesis and decreases the level of mitophagy-related proteins, parkin and PTEN-induced putative kinase 1. Afzelin improves the survival rate and reduces the serum levels of alanine aminotransferase and pro-inflammatory cytokines in D-galactosamine (GalN)/LPS -treated mice[1].

  • CAS Number: 482-39-3
  • MF: C21H20O10
  • MW: 432.378
  • Catalog: Mitochondrial Metabolism
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 765.6±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 272.4±26.4 °C

PI3K/mTOR Inhibitor-3

PI3K/mTOR Inhibitor-3 (compound 12), an imidazoline, is a potent PI3K and mTOR dual inhibitor. PI3K/mTOR Inhibitor-3 has anti-cancer activity[1].

  • CAS Number: 1363338-53-7
  • MF: C22H23N5O
  • MW: 373.45
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KU 60019

KU-60019 is an improved ATM kinase-specific inhibitor with IC50 of 6.3 nM.

  • CAS Number: 925701-46-8
  • MF: C30H33N3O5S
  • MW: 547.665
  • Catalog: ATM/ATR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 786.6±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 429.5±32.9 °C

Hematein

Hematein is a oxidation product of hematoxylin acted as a dye[1]. Hematein is an allosteric casein kinase II inhibitor with an IC50 of 0.74 μM. Hematein inhibits Akt/PKB Ser129 phosphorylation, the Wnt/TCF pathway and increases apoptosis in lung cancer cells[2].

  • CAS Number: 475-25-2
  • MF: C16H12O6
  • MW: 300.26300
  • Catalog: Apoptosis
  • Density: 1.77g/cm3
  • Boiling Point: 753.1ºC at 760mmHg
  • Melting Point: 180ºC
  • Flash Point: 289ºC

AMPK-α1β1γ1 activator 1

AMPK-α1β1γ1 activator 1 (M1) is an acyl glucuronide metabolite of Indole-3-carboxylic Acid-based AMPK activator. AMPK-α1β1γ1 activator 1 can selectively activated human β1 isoforms with an EC50 value of 38.1nM. AMPK-α1β1γ1 activator 1 can direct binding with human AMPK α1β1γ1 isoform. AMPK-α1β1γ1 activator 1 can be used for the research of diabetic nephropathy[1].

  • CAS Number: 1943510-86-8
  • MF: C25H24ClNO9
  • MW: 517.91
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Coelonin

Coelonin is a dihydrophenanthrene with anti-inflammation activity. Coelonin inhibits LPS-induced PTEN phosphorylation. Coelonin inhibits NF-κB activation and p27Kip1 degradation by regulating the PI3K/AKT pathway negatively. Coelonin can inhibit IκBα phosphorylation and degradation and increases the expression of IκBα protein[1][2].

  • CAS Number: 82344-82-9
  • MF: C15H14O3
  • MW: 242.27000
  • Catalog: Interleukin Related
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A