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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Everolimus (RAD001)

Everolimus (RAD001) is a potent mTOR inhibitor that binds to FKBP-12 to generate an immunosuppressive complex.

  • CAS Number: 159351-69-6
  • MF: C53H83NO14
  • MW: 958.224
  • Catalog: mTOR
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 998.7±75.0 °C at 760 mmHg
  • Melting Point: NA
  • Flash Point: 557.8±37.1 °C

YU238259

YU238259 is an inhibitor of homology-dependent DNA repair (HDR), used for cancer research.

  • CAS Number: 1943733-16-1
  • MF: C22H22ClN3O4S
  • MW: 459.9525
  • Catalog: DNA-PK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

STX-478

STX-478 (compound 80) is an oral CNS-penetrant allosteric mutant-selective PI3Kα inhibitor. STX-478 STX-478 shows robust and durable tumor regression and can be used in cancer research[1].

  • CAS Number: 2883540-92-7
  • MF: C16H12F5N5O2
  • MW: 401.29
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

mTOR Inhibitor 1

mTOR Inhibitor 1 is a highlt potent, selective and oral mTOR inhibitor with an IC50 of 7 nM. mTOR Inhibitor 1 inhibits cellular phosphorylation of mTORC1 (pS6 and p4E-BP1) and mTORC2 (pAKT (S473)) substrates[1].

  • CAS Number: 2219323-96-1
  • MF: C23H21N7O
  • MW: 411.46
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Yuanhuadin

Yuanhuadin, extracted from Genkwa Flos Daphne genkwa, has antitumor activity through inhibiting Akt/mTOR and EGFR pathways, induce cell-cycle arrest and abortion[1].

  • CAS Number: 76402-66-9
  • MF: C32H42O10
  • MW: 586.67000
  • Catalog: EGFR
  • Density: 1.34g/cm3
  • Boiling Point: 704.4ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 222.4ºC

PI3K/mTOR Inhibitor-5

PI3K/mTOR Inhibitor-5 (compound 19a) is a potent and dual PI3K and mTOR inhibitor, with IC50 values of 86.9 nM and 14.6 nM, respectively[1].

  • CAS Number: 2456295-60-4
  • MF: C32H40N10O3
  • MW: 612.73
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1-(2-hydroxy-4-morpholin-4-ylphenyl)ethanone

IC 86621 is a potent DNA-dependent protein kinase (DNA-PK) inhibitor, with an IC50 of 120 nM. IC 86621 also acts as a selective and reversible ATP-competitive inhibitor.IC 86621 inhibits DNA-PK mediated cellular DNA double-strand break (DSB) repair (EC50=68 µM). IC 86621 increases DSB-induced antitumor activity without cytotoxic effects. IC 86621 can protects rheumatoid arthritis (RA) T cells from apoptosis[1][2].

  • CAS Number: 404009-40-1
  • MF: C12H15NO3
  • MW: 221.252
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 425.5±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 211.1±28.7 °C

Quercetin D5

Quercetin D5 is a deuterium labeled Quercetin. Quercetin, a natural flavonoid, is a stimulator of recombinant SIRT1 and also a PI3K inhibitor with IC50 of 2.4 μM, 3.0 μM and 5.4 μM for PI3K γ, PI3K δ and PI3K β, respectively[1].

  • CAS Number: 263711-78-0
  • MF: C15H5D5O7
  • MW: 307.27
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

WYE 687 dihydrochloride

WYE-687 dihydrochloride is an ATP-competitive mTOR inhibitor with an IC50 of 7 nM[1]. WYE-687 dihydrochloride concurrently inhibits activation of mTORC1 and mTORC2[2]. WYE-687 also inhibits PI3Kα and PI3Kγ with IC50s of 81 nM and 3.11 μM, respectively[1].

  • CAS Number: 1702364-87-1
  • MF: C28H34Cl2N8O3
  • MW: 601.53
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TD52

TD52, an Erlotinib (HY-50896) derivative, is an orally active, potent cancerous inhibitor of protein phosphatase 2A (CIP2A) inhibitor. TD52 mediates the apoptotic effect in triple-negative breast cancer (TNBC) cells via regulating the CIP2A/PP2A/p-Akt signalling pathway. TD52 indirectly reduced CIP2A by disturbing Elk1 binding to the CIP2A promoter. TD52 has less p-EGFR inhibition and has potent anti-cancer activity[1].

  • CAS Number: 1798328-24-1
  • MF: C24H16N4
  • MW: 360.41
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AZD1080

AZD1080 is a potent and selective GSK3 inhibitor. AZD1080 inhibits recombinant human GSK3α and GSK3β with pKi (IC50) of 8.2 (6.9 nM) and 7.5 (31 nM), respectively.

  • CAS Number: 612487-72-6
  • MF: C19H18N4O2
  • MW: 334.372
  • Catalog: GSK-3
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 594.0±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 313.0±30.1 °C

CC-115

CC-115 is a potent and dual DNA-PK and mTOR kinase inhibitor with IC50s of 13 nM and 21 nM, respectively. CC-115 blocks both mTORC1 and mTORC2 signaling.

  • CAS Number: 1228013-15-7
  • MF: C16H16N8O
  • MW: 336.35100
  • Catalog: DNA-PK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A
  • CAS Number: 1043881-55-5
  • MF: C66H110N15O20P
  • MW: 1464.665
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

peruvoside

Peruvoside is a potent inhibitor of Src, PI3K, JNK, STAT, and EGFR. Peruvoside induces apoptosis and autophagy and possesses a broad spectrum of anticancer activity in breast, lung, liver cancers and leukemia. Peruvoside is a broad-spectrum and potent antiviral activity against positive-sense RNA viruses. Peruvoside sensitizes Gefitinib (HY-50895)-resistant tumour cells (A549, PC9/gef and H1975) to Gefitinib[1][2][3][4].

  • CAS Number: 1182-87-2
  • MF: C30H44O9
  • MW: 548.66
  • Catalog: Apoptosis
  • Density: 1.31g/cm3
  • Boiling Point: 731.6ºC at 760 mmHg
  • Melting Point: 161-164ºC
  • Flash Point: 236.2ºC

Boc-L-Cyclobutylglycine

Boc-L-cyclobutylglycine is a glycine derivative that can be used for PI3K inhibitor synthesis[1].

  • CAS Number: 155905-77-4
  • MF: C11H19NO4
  • MW: 229.273
  • Catalog: PI3K
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 379.1±25.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 183.1±23.2 °C

MT6378

MT 63-78 is a specific and potent direct AMPK activator with an EC50 of 25 μM. MT 63–78 also induces cell mitotic arrest and apoptosis. MT 63-78 blocks prostate cancer growth by inhibiting the lipogenesis and mTORC1 pathways. MT 63-78 has antitumor effects[1].

  • CAS Number: 1179347-65-9
  • MF: C21H14N2O2
  • MW: 326.35
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AQX-016A

AQX-016A is an orally active and potent SHIP1 agonist. AQX-016A can activate recombinant SHIP1 enzyme in vitro and stimulate SHIP1 activity. AQX-016A also can inhibit the PI3K pathway and TNFa production, can be useful for various inflammatory diseases research[1][2].

  • CAS Number: 849669-54-1
  • MF: C22H32O2
  • MW: 328.49
  • Catalog: Phosphatase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Euscaphic acid

Euscaphic acid, a DNA polymerase inhibitor, is a triterpene from the root of the R. alceaefolius Poir. Euscaphic inhibits calf DNA polymerase α (pol α) and rat DNA polymerase β (pol β) with IC50 values of 61 and 108 μM[1]. Euscaphic acid induces apoptosis[2].

  • CAS Number: 53155-25-2
  • MF: C30H48O5
  • MW: 488.699
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 602.7±55.0 °C at 760 mmHg
  • Melting Point: 262-264℃
  • Flash Point: 332.3±28.0 °C

PI3Kδ-IN-10

PI3Kδ-IN-10 is a highly potent and orally active PI3Kδ inhibitor with IC50 of 2 nM. PI3Kδ-IN-10 robustly suppresses the downstream AKT pathway to induce subsequent apoptosis in hepatocellular carcinoma models[1].

  • CAS Number: 2409725-49-9
  • MF: C19H16ClN9
  • MW: 405.84
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

9-ING-41

9-ING-41 is a potent glycogen synthase kinase-3 (GSK-3) inhibitor[1]. 9-ING-41 induces apoptosis and cell cycle arrest at prophase by targeting centrosomes and microtubule-bound GSK-3β. 9-ING-41 has anticancer activity[2].

  • CAS Number: 1034895-42-5
  • MF: C22H13FN2O5
  • MW: 404.34700
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cenisertib

Cenisertib (AS-703569) is a multi-kinase inhibitor that blocks the activity of Aurora-kinase-A/B, ABL1, AKT, STAT5 and FLT3. Cenisertib induces major growth-inhibitory effects by blocking the activity of several different molecular targets in neoplastic mast cells (MC)[1]. Cenisertib inhibits tumor growth in xenograft models of pancreatic, breast, colon, ovarian, and lung tumors and leukemia[2].

  • CAS Number: 871357-89-0
  • MF: C24H30FN7O
  • MW: 451.540
  • Catalog: Aurora Kinase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 708.3±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 382.2±35.7 °C

PI3K/Akt/CREB activator 1

PI3K/Akt/CREB activator 1 (compound AE-18) is a potent, orally active PI3K/Akt/CREB activator. PI3K/Akt/CREB activator 1 promotes neuronal proliferation, induced differentiation of Neuro-2a cells into a neuron-like morphology, and accelerated the establishment of axon-dendrite polarization of primary hippocampal neurons through upregulating brain-derived neurotrophic factor via the PI3K/Akt/CREB pathway. PI3K/Akt/CREB activator 1 can be used in research of vascular dementia (VaD)[1].

  • CAS Number: 2708177-73-3
  • MF: C19H15F4NO3
  • MW: 381.32
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AZ20

AZ20 is a potent and selective inhibitor of ATR with an IC50 of 5 nM, and has 8-fold selectivity against mTOR (IC50=38 nM).

  • CAS Number: 1233339-22-4
  • MF: C21H24N4O3S
  • MW: 412.505
  • Catalog: ATM/ATR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 634.6±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 337.6±31.5 °C

PIK-75

PIK-75 is a reversible DNA-PK and p110α-selective inhibitor, which inhibits DNA-PK, p110α and p110γ with IC50s of 2, 5.8 and 76 nM, respectively. PIK-75 inhibits p110α >200-fold more potently than p110β (IC50=1.3 μM)[1][2]. PIK-75 induces apoptosis[3].

  • CAS Number: 372196-67-3
  • MF: C16H14BrN5O4S
  • MW: 452.283
  • Catalog: Apoptosis
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI3K/Akt/mTOR-IN-2

PI3K/Akt/mTOR-IN-2 is a PI3K/AKT/mTOR pathway inhibitor. PI3K/Akt/mTOR-IN-2 possess anti-cancer effects and selectivity against MDA-MB-231 cells with IC50 value of 2.29 μM. PI3K/Akt/mTOR-IN-2 can induce cancer cell cycle arrest and apoptosis[1].

  • CAS Number: 2757804-89-8
  • MF: C17H13F2NO
  • MW: 285.29
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(3β,5α,6β)-Androstane-3,5,6-triol

5α-Androstane-3β,5,6β-triol is a neuroprotectant. 5α-Androstane-3β,5,6β-triol can remarkably reverse intracellular acidification and alleviate neuronal injury through the inhibition of AMPK signaling. 5α-Androstane-3β,5,6β-triol remarkably reduced the infarct volume and attenuated neurologic impairment in acute ischemic stroke models of middle cerebral artery occlusion in vivo[1].

  • CAS Number: 4725-51-3
  • MF: C19H32O3
  • MW: 308.456
  • Catalog: AMPK
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 430.1±35.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 193.1±20.5 °C

Rutundic acid

Rotundic acid, a triterpenoid obtained from I. rotunda, induces DNA damage and cell apoptosis in hepatocellular carcinoma through AKT/mTOR and MAPK Pathways. Rotundic acid possesses anti-inflammatory and cardio-protective abilities[1].

  • CAS Number: 20137-37-5
  • MF: C30H48O5
  • MW: 488.699
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 622.8±55.0 °C at 760 mmHg
  • Melting Point: 272-274℃
  • Flash Point: 344.5±28.0 °C

Thioether-cyclized helix B peptide, CHBP

Thioether-cyclized helix B peptide, CHBP can improve metabolic stability and renoprotective effect through inducing autophagy via inhibition of mTORC1 and activation of mTORC2[1].

  • CAS Number: 1453840-35-1
  • MF: C56H93N19O22S
  • MW: 1416.52
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ATM Inhibitor-5

ATM Inhibitor-5 [formula (1)] is a potent inhibitor of serine/threonine protein kinase ATM (extracted from patent WO2022058351A1)[1].

  • CAS Number: 2495096-26-7
  • MF: C23H21FN6O3
  • MW: 448.45
  • Catalog: ATM/ATR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KP-23172

KP-23172 is a PI3-K/Akt pathway inhibitor extracted from patent US7196083[1].

  • CAS Number: 331253-86-2
  • MF: C10H4N6O
  • MW: 224.17800
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A