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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PARP/PI3K-IN-1

PARP/PI3K-IN-1 (compound 15) is a potent PARP/PI3K inhibitor with pIC50 values of 8.22, 8.44, 8.25, 6.54, 8.13, 6.08 for PARP-1, PARP-2, PI3Kα, PI3Kβ, PI3Kδ, and PI3Kγ, respectively. PARP/PI3K-IN-1 is a highly effective anticancer compound targeted against a wide range of oncologic diseases[1].

  • CAS Number: 2337386-47-5
  • MF: C33H28F4N8O3
  • MW: 660.62
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI 828

PI-828 is a dual PI3K and casein kinase 2 (CK2) inhibitor with IC50s of 173 nM, 149 nM, and 1127 nM for p110α, CK2, and CK2α2 in lipid kinase assay, respectively[1].

  • CAS Number: 942289-87-4
  • MF: C19H18N2O3
  • MW: 322.35800
  • Catalog: PI3K
  • Density: 1.316g/cm3
  • Boiling Point: 534.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 276.9ºC

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

NIBR-17

NIBR-17 is a pan-class I PI3K inhibitor with suitable pharmacokinetic properties and inhibits tumor growth[1].

  • CAS Number: 944396-88-7
  • MF: C18H20N8O2
  • MW: 380.40
  • Catalog: PI3K
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 718.3±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 388.2±35.7 °C

UCL-TRO-1938

UCL-TRO-1938 is a potent allosteric activator of PI3Kα with an EC50 value of approximately 60 μM. UCL-TRO-1938 can induce cell proliferation and has cardioprotective and neural regeneration effects[1].

  • CAS Number: 2919575-27-0
  • MF: C27H32N6O
  • MW: 456.58
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

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

PI3K-IN-31

PI3K-IN-31 (Compound 6b) is a potent PI3K inhibitor with IC50s of 3.7 nM, 74 nM, 14.6 nM, and 9.9 nM for PI3Kα, PI3Kβ, PI3Kγ, and PI3Kδ, respectively. PI3K-IN-31 has anticancer effects[1].

  • CAS Number: 1359956-12-9
  • MF: C19H23F2N7O3
  • MW: 435.43
  • Catalog: PI3K
  • 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

OSI-027

OSI-027 is an ATP-competitive mTOR kinase activity inhibitor with an IC50 of 4 nM. OSI-027 targets both mTORC1 and mTORC2 with IC50s of 22 nM and 65 nM, respectively.

  • CAS Number: 936890-98-1
  • MF: C21H22N6O3
  • MW: 406.438
  • Catalog: Autophagy
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 591.4±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 311.5±32.9 °C

RLY-2608

RLY-2608 is a first-in-class allosteric mutant-selective inhibitor of PI3Ka[1].

  • CAS Number: 2733573-94-7
  • MF: C29H14ClF5N6O2
  • MW: 608.91
  • Catalog: PI3K
  • Density: N/A
  • 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

PI3K-IN-36

PI3K-IN-36 (compound A36) is a potent PI3K inhibitor. PI3K-IN-36 can be used in research of follicular lymphoma (FL)[1].

  • CAS Number: 1401436-93-8
  • MF: C30H36F2N8O
  • MW: 562.66
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Guggulsterone E&Z

Guggulsterone is a plant sterol derived from the gum resin of the tree Commiphora wightii. Guggulsterone inhibits the growth of a wide variety of tumor cells and induces apoptosis through down regulation of antiapoptotic gene products (IAP1, xIAP, Bfl-1/A1, Bcl-2, cFLIP and survivin), modulation of cell cycle proteins (cyclin D1 and c-Myc), activation of caspases and JNK, inhibition of Akt[1]. Guggulsterone, a farnesoid X receptor (FXR) antagonist, decreases CDCA-induced FXR activation with IC50s of 17 and 15 μM for Z- and E-Guggulsterone, respectively[2].

  • CAS Number: 95975-55-6
  • MF: C21H28O2
  • MW: 312.446
  • Catalog: Apoptosis
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 463.3±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 172.3±25.7 °C

ATR-IN-24

ATR-IN-24 (Compound 1) is a ATR inhibitor. ATR-IN-24 has anticancer activity[1].

  • CAS Number: 2370889-43-1
  • MF: C23H26N6O2
  • MW: 418.49
  • Catalog: ATM/ATR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

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

MIPS-21335

MIPS-21335 is an PI3KC2α inhibitor (IC50: 7 nM). MIPS-21335 also inhibits PI3KC2β, p110α, p110β and p110δ (IC50: 0.043, 0.140, 0.386, 0.742 μM). MIPS-21335 has antithrombotic effect[1].

  • CAS Number: 2569296-51-9
  • MF: C24H21N7O5
  • MW: 487.47
  • Catalog: PI4K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BGT226 free base

BGT226 (NVP-BGT226) is a PI3K (with IC50s of 4 nM, 63 nM and 38 nM for PI3Kα, PI3Kβ and PI3Kγ)/mTOR dual inhibitor which displays potent growth-inhibitory activity against human head and neck cancer cells[1][2].

  • CAS Number: 915020-55-2
  • MF: C28H25F3N6O2
  • MW: 534.53
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 713.3±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 385.2±35.7 °C

Bikinin

Bikinin is a non-steroidal, ATP-competitive inhibitor of plant GSK-3/Shaggy-like kinases and activates BR (brassinosteroids) signaling.

  • CAS Number: 188011-69-0
  • MF: C9H9BrN2O3
  • MW: 273.083
  • Catalog: GSK-3
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 521.6±45.0 °C at 760 mmHg
  • Melting Point: 144°C(lit.)
  • Flash Point: 269.2±28.7 °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

CGS 15943

CGS 15943 is an adenosine A2 receptor antagonist and reduces stroke injury in the Mongolian gerbil[1]. CGS 15943 is a selectively p110γ inhibitor with an IC50 of 1.1 μM, shows inhibitory effect on p110δ (IC50=8.47 μM), has an anti-carcinogenic effect on HCC and PDAC cells[2].

  • CAS Number: 104615-18-1
  • MF: C13H8ClN5O
  • MW: 285.68900
  • Catalog: Adenosine Receptor
  • Density: 1.72 g/cm3
  • Boiling Point: 566.6ºC at 760 mmHg
  • Melting Point: 278-279 °C
  • Flash Point: 296.5ºC

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

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

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

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