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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AKTide-2T TFA

AKTide-2T is an excellent in vitro substrate for AKT and shows competitive inhibition of histone H2B phosphorylation with a Ki of 12 nM. AKTide-2T mimics the optimal phosphorylation sequence of Akt and is an inhibitory peptide with the wildtype AKTide lacking Thr in the S22 position[1].

  • CAS Number: 324029-01-8
  • MF: C74H114N28O20
  • MW: 1715.87000
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 153-156ºC
  • Flash Point: N/A

UCB9608

UCB9608 is a potent, selective and orally active PI4KIIIβ inhibitor, with an IC50 of 11 nM, selective over PI3KC2 α, β, and γ lipid kinases. UCB9608 improves metabolic stability and exhibits excellent pharmacokinetic profile, acts as a potent immunosuppressive agent[1].

  • CAS Number: 1616413-96-7
  • MF: C20H26N8O2
  • MW: 410.47
  • Catalog: PI4K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PX-866

Sonolisib (PX-866), an improved Wortmannin analogue, is an oral, irreversible, and pan-isoform inhibitor of PI3K (IC50=0.1 nM (p110α), 1.0 nM (p120γ), 2.9 nM (p110δ)). Antitumor activity[1][2].

  • CAS Number: 502632-66-8
  • MF: C29H35NO8
  • MW: 525.590
  • Catalog: PI3K
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 651.4±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 347.7±31.5 °C

Copanlisib dihydrochloride

Copanlisib dihydrochloride (BAY 80-6946 dihydrochloride) is a potent, selective and ATP-competitive pan-class I PI3K inhibitor, with IC50s of 0.5 nM, 0.7 nM, 3.7 nM and 6.4 nM for PI3Kα, PI3Kδ, PI3Kβ and PI3Kγ, respectively. Copanlisib dihydrochloride has more than 2,000-fold selectivity against other lipid and protein kinases, except for mTOR. Copanlisib dihydrochloride has superior antitumor activity[1].

  • CAS Number: 1402152-13-9
  • MF: C23H30Cl2N8O4
  • MW: 553.442
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK-3β inhibitor 2

GSK-3β inhibitor 2 (Compound 3) is a potent, selective and orally active GSK-3β inhibitor with an IC50 of 1.1 nM. GSK-3β inhibitor 2 can cross the blood-brain barrier. GSK-3β inhibitor 2 has the potential for Alzheimer's disease[1].

  • CAS Number: 1702428-31-6
  • MF: C14H14N4O3S
  • MW: 318.35
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Doxorubicin hydrochloride

Doxorubicin is a cytotoxic anthracycline antibiotic for the treatment of multiple cancers. The possible mechanisms by which doxorubicin acts in the cancer cell are intercalation into DNA and disruption of topoisomerase-II-mediated DNA repair.

  • CAS Number: 23214-92-8
  • MF: C27H29NO11
  • MW: 543.52
  • Catalog: Bacterial
  • Density: 1.61 g/cm3
  • Boiling Point: N/A
  • Melting Point: 205ºC
  • Flash Point: 443.8ºC

PI3K/AKT-IN-2

PI3K/AKT-IN-2 (Compound 12c) is a PI3K and AKT inhibitor. PI3K/AKT-IN-2 blocks the epithelial-mesenchymal transition (EMT) and induces apoptosis. PI3K/AKT-IN-2 inhibits the polymerization of tubulin[1].

  • CAS Number: 2684412-41-5
  • MF: C32H27BrO10
  • MW: 651.45
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Kihadanin B

Kihadanin B is a citrus limonoid that can be purified from the peels of immature Citrus unshiu. Kihadanin B suppresses adipogenesis through repression of the Akt-FOXO1-PPARγ axis in 3T3-L1 adipocytes[1].

  • CAS Number: 73793-68-7
  • MF: C26H30O9
  • MW: 486.51100
  • Catalog: PPAR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SAR-405

SAR405 is a PIK3C3/Vps34 inhibitor with an IC50 of 1.2 nM. SAR405 prevents autophagy and synergizes with MTOR inhibition in tumor cells.

  • CAS Number: 1523406-39-4
  • MF: C19H21ClF3N5O2
  • MW: 443.850
  • Catalog: Autophagy
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 526.5±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 272.2±32.9 °C

ZL-2201

ZL-2201 is a potent DNA-PK inhibitor with an IC50 of 1 nM (WO2021104277A1, compound 5)[1].

  • CAS Number: 2865115-39-3
  • MF: C20H25N9O5S
  • MW: 503.53
  • Catalog: DNA-PK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

mTOR inhibitor-13

mTOR inhibitor-13 (compound 9g), an aryl ureido compound, is a potent and selective mTOR inhibitor with an IC50 of 0.29 nM. mTOR inhibitor-13 also inhibits PI3K-α with an IC50 of 119 nM[1].

  • CAS Number: 1144075-44-4
  • MF: C24H22N6O2S
  • MW: 458.54
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CHIR 99021 trihydrochloride

CHIR-99021 trihydrochloride is a GSK-3α/β inhibitor with IC50 of 10 nM/6.7 nM; > 500-fold selectivity for GSK-3 versus its closest homologs CDC2 and ERK2, as well as other protein kinases.

  • CAS Number: 1782235-14-6
  • MF: C22H21Cl5N8
  • MW: 574.721
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Compound 401

Compound 401 is a synthetic inhibitor of DNA-PK (IC50 = 0.28 μM) that also targets mTOR but not PI3K in vitro.

  • CAS Number: 168425-64-7
  • MF: C16H15N3O2
  • MW: 281.309
  • Catalog: DNA-PK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 456.9±55.0 °C at 760 mmHg
  • Melting Point: 214 °C
  • Flash Point: 230.1±31.5 °C

PF-06885249

PF-249 is a potent, selective AMPK β1-containing complexes activator; increases the phosphorylation of the AMPK substrate ACC at S79 with EC50 of 296 nM, potently inhibits de novo lipogenesis (IC50=15 nM) in primary rat hepatocytes.

  • CAS Number: 1467059-70-6
  • MF: C17H16ClN3O3
  • MW: 345.783
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HL271

HL271, a chemical derivative of metformin (HY-B0627), is a potent AMPK activator that increases AMPK phosphorylation. HL271 attenuates aging-associated cognitive impairment[1][2].

  • CAS Number: 1422365-52-3
  • MF: C13H17ClF3N5O
  • MW: 351.76
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TWS119

TWS119 is a specific inhibitor of GSK-3β, with an IC50 of 30 nM, and activates the wnt/β-catenin pathway.

  • CAS Number: 601514-19-6
  • MF: C18H14N4O2
  • MW: 318.329
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 646.0±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 344.5±31.5 °C

BX-320

BX-320 is a selective, ATP-competitive, orally acitive, and direct PDK1 inhibitor with an IC50 of 30 nM in a direct kinase assay format. BX-320 also induces apoptosis. Anticancer effect[1].

  • CAS Number: 702676-93-5
  • MF: C23H31BrN8O3
  • MW: 547.44800
  • Catalog: PDK-1
  • Density: 1.484g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK3β inhibitor II

GSK3β inhibitor II is an inhibitor of GSK3β. GSK3β inhibitor II can be used for research of Alzheimer’s disease (AD)[1].

  • CAS Number: 478482-75-6
  • MF: C14H10IN3OS
  • MW: 395.21800
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SY-LB-35

SY-LB-35 is a potent bone morphogenetic protein (BMP) receptor agonist. SY-LB-35 can stimulate significant increases in cell number and cell viability in the C2C12 myoblast cell line, and causes shifts towards the S and G2/M phases of the cell cycle. SY-LB-35 stimulates canonical Smad and non-canonical PI3K/Akt, ERK, p38 and JNK intracellular signaling pathways[1].

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

AZD 3147

AZD3147 is a potent, orally active, selective dual inhibitor of mTORC1 and mTORC2 with an IC50 value of 1.5 nM. AZD3147 also has a selective effect on PI3K[1].

  • CAS Number: 1101810-02-9
  • MF: C24H31N5O4S2
  • MW: 517.664
  • Catalog: mTOR
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 696.7±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 375.2±34.3 °C

Hu7691 free base

Hu7691 free base is an orally active, selective Akt inhibitor with IC50s of 4.0 nM, 97.5 nM, 28 nM for Akt1, Akt2 and Akt3, respectively. Hu7691 free base inhibits tumor growth and enables decrease of cutaneous toxicity in mice[1].

  • CAS Number: 2241232-43-7
  • MF: C22H21F3N4O
  • MW: 414.42
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GNE-490

GNE-490, a (thienopyrimidin-2-yl)aminopyrimidine, is a potent pan-PI3K inhibitor with IC50s of 3.5 nM, 25 nM, 5.2 nM, 15 nM for  PI3Kα, PI3Kβ, PI3Kδ and PI3Kγ, respectively. GNE-490 has >200 fold selectivity for mTOR (IC50=750 nM). GNE-490 shows potent suppression efficacy profile against MCF7.1 breast cancer xenograft model[1].

  • CAS Number: 1033739-92-2
  • MF: C18H22N6O2S
  • MW: 386.47
  • Catalog: mTOR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 595.3±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 313.9±32.9 °C

FPA 124

FPA-124, a cell-permeable copper complex, is a selective Akt inhibitor with an IC50 of 0.1 μM. FPA-124 interacts with both the pleckstrin homology (PH) and the kinase domains of Akt. FPA-124 induces apoptosis[1][2].

  • CAS Number: 902779-59-3
  • MF: C11H9Cl2CuN3O2S
  • MW: 381.72500
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5-Iodo-indirubin-3'-monoxime

5-Iodo-indirubin-3'-monoxime is a potent GSK-3β, CDK5/P25 and CDK1/cyclin B inhibitor, competing with ATP for binding to the catalytic site of the kinase, with IC50s of 9, 20 and 25 nM, respectively[1].

  • CAS Number: 331467-03-9
  • MF: C16H10IN3O2
  • MW: 403.17
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SB203580

SB 203580 is a widely used p38 MAPK inhibitor with an IC50 of 0.3-0.5 μM. It shows more than 100-fold selectivity over PKB, LCK, and GSK-3β.

  • CAS Number: 152121-47-6
  • MF: C21H16FN3OS
  • MW: 377.435
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 615.6±55.0 °C at 760 mmHg
  • Melting Point: 249 - 250ºC
  • Flash Point: 326.1±31.5 °C

Batatasin III

Batatasin III, a stilbenoid, inhibits cancer migration and invasion by suppressing epithelial to mesenchymal transition (EMT) and FAK-AKT Signals. Batatasin III has anti-cancer activities[1].

  • CAS Number: 56684-87-8
  • MF: C16H18O3
  • MW: 258.31200
  • Catalog: Akt
  • Density: 1.126g/cm3
  • Boiling Point: 406.1ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 199.4ºC

β-Glycerol phosphate disodium salt pentahydrate

β-Glycerol phosphate disodium salt pentahydrate is a Phosphatase and tensin homolog (PTEN) inhibitor extracted from patent US 20110002877 A1.

  • CAS Number: 13408-09-8
  • MF: C3H19Na2O11P
  • MW: 308.13
  • Catalog: PTEN
  • Density: N/A
  • Boiling Point: 488.2ºC at 760mmHg
  • Melting Point: >300ºC
  • Flash Point: 249.1ºC

GNE-293

GNE-293 is a potent and selective PI3Kδ inhibitor with Ki of 0.47 nM, displays 256, 420, 219-fold selectivity over PI3Kα, PI3Kβ, PI3Kγ, respectively; exhibits excellent potency in human whole blood (HWB) assay (CD69 HWB IC50=4.38 nM); possesses favorable pharmacokinetic properties and orally bioavailable.

  • CAS Number: 1354955-67-1
  • MF: C28H36N8O4S
  • MW: 580.702
  • Catalog: PI3K
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 853.5±75.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 470.0±37.1 °C

Eganelisib(IPI-549)

IPI549 is a potent and selective PI3Kγ inhibitor with an IC50 of 16 nM.

  • CAS Number: 1693758-51-8
  • MF: C30H24N8O2
  • MW: 528.576
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pi3kd/v-in-01

PI3KD/V-IN-01 is a potent ATP-competitive PI3Kδ/Vps34 dual inhibitor.

  • CAS Number: 1807551-44-5
  • MF: C21H24ClN5O3S2
  • MW: 494.03
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A