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.


Anti-infection >
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Antibody-drug Conjugate >
ADC Cytotoxin ADC Linker Drug-Linker Conjugates for ADC PROTAC-linker Conjugate for PAC
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JAK/STAT Signaling >
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Metabolic Enzyme/Protease >
15-PGDH 5 alpha Reductase 5-Lipoxygenase Acetyl-CoA Carboxylase Acyltransferase Adenosine Deaminase Adenosine Kinase Aldehyde Dehydrogenase (ALDH) Aldose Reductase Aminopeptidase Angiotensin-converting Enzyme (ACE) ATGL ATP Citrate Lyase Carbonic Anhydrase Carboxypeptidase Cathepsin CETP COMT Cytochrome P450 Dipeptidyl Peptidase Dopamine β-hydroxylase E1/E2/E3 Enzyme Elastase Enolase FAAH FABP Factor Xa Farnesyl Transferase Fatty Acid Synthase (FAS) FXR Glucokinase GSNOR Gutathione S-transferase HCV Protease Hexokinase HIF/HIF Prolyl-Hydroxylase HIV Integrase HIV Protease HMG-CoA Reductase (HMGCR) HSP Indoleamine 2,3-Dioxygenase (IDO) Isocitrate Dehydrogenase (IDH) Lactate Dehydrogenase LXR MAGL Mineralocorticoid Receptor Mitochondrial Metabolism MMP Nampt NEDD8-activating Enzyme Neprilysin PAI-1 PDHK PGC-1α Phosphatase Phosphodiesterase (PDE) Phospholipase Procollagen C Proteinase Proteasome Pyruvate Kinase RAR/RXR Renin ROR Ser/Thr Protease SGK Stearoyl-CoA Desaturase (SCD) Thrombin Tryptophan Hydroxylase Tyrosinase Xanthine Oxidase
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NF-κB >
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PI3K/Akt/mTOR >
Akt AMPK ATM/ATR DNA-PK GSK-3 MELK mTOR PDK-1 PI3K PI4K PIKfyve PTEN
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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

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

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

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

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

MPT0E028

MPT0E028 is an orally active and selective HDAC inhibitor with IC50s of 53.0 nM, 106.2 nM, 29.5 nM for HDAC1, HDAC2 and HDAC6, respectively[1]. MPT0E028 reduces the viability of B-cell lymphomas by inducing apoptosis and possesses potent direct Akt targeting ability and reduces Akt phosphorylation in B-cell lymphoma. MPT0E028 has good anticancer activity[2].

  • CAS Number: 1338320-94-7
  • MF: C17H16N2O4S
  • MW: 344.38500
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Perifosine (KRX-0401)

Perifosine is an oral Akt inhibitor. All cells are sensitive to the antiproliferative properties of Perifosine with an IC50 of ~0.6-8.9 μM.

  • CAS Number: 157716-52-4
  • MF: C25H52NO4P
  • MW: 461.658
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 271-272° (dec)
  • Flash Point: N/A

PI3K-IN-9

PI3K-IN-9 (compound 1-14) is a potent and selective PI3Kδ inhibitor with an IC50 of 8.9 nM[1].

  • CAS Number: 2360875-63-2
  • MF: C19H23N7O
  • MW: 365.43
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI3K/mTOR Inhibitor-14

PI3K/mTOR Inhibitor-14 (compound Y-2) is a potent PI3K and mTOR dual inhibitor with IC50s of 171.4 nM and 10.1 nM, respectively. PI3K/mTOR Inhibitor-14 has antitumor activities[1].

  • CAS Number: 2919684-77-6
  • MF: C28H30N8O3S
  • MW: 558.65
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MK-2206 2HCl

MK 2206 is an orally active allosteric Akt inhibitor with IC50s of 5, 12 and 65 nM for Akt1, Akt2 and Akt3, respectively.

  • CAS Number: 1032350-13-2
  • MF: C25H23Cl2N5O
  • MW: 480.389
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L-Leucine-13C6

L-Leucine-13C6 is the 13C labeled L-Leucine[1]. L-Leucine is an essential branched-chain amino acid (BCAA), which activates the mTOR signaling pathway[2].

  • CAS Number: 201740-84-3
  • MF: 13C6H13NO2
  • MW: 137.129
  • Catalog: mTOR
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Kazinol B

Kazinol B, a prenylated flavan with a dimethyl pyrane ring, is an inhibitor of nitric oxide (NO) production. Kazinol B improves insulin sensitivity by enhancing glucose uptake via the insulin-Akt signaling pathway and AMPK activation. Kazinol B has the potential for diabetes mellitus research[1][2].

  • CAS Number: 99624-27-8
  • MF: C25H28O4
  • MW: 392.487
  • Catalog: AMPK
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 556.6±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 290.4±30.1 °C

Demethyleneberberine

Demethyleneberberine is a natural mitochondria-targeted antioxidant. Demethyleneberberine alleviates mice colitis and inhibits the inflammatory responses by inhibiting NF-κB pathway and regulating the balance of Th cells. Demethyleneberberine could serve as a AMPK activator for treating non-alcoholic fatty liver disease (NAFLD)[1][2][3].

  • CAS Number: 25459-91-0
  • MF: C19H18NO4+
  • MW: 323.34300
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Etilefrin

Etilefrine (3-[2-(ethylamino)-1-hydroxyethyl]phenol) is an α adrenergic agonist[2]. Etilefrine also is an AMPK activator[1]. Etilefrine can be used for the research of postural hypotension[3].

  • CAS Number: 709-55-7
  • MF: C10H15NO2
  • MW: 181.23200
  • Catalog: AMPK
  • Density: 1.127 g/cm3
  • Boiling Point: 351.7ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 155.5ºC

Methyl cinnamate

Methyl cinnamate (Methyl 3-phenylpropenoate), an active component of Zanthoxylum armatum, is a widely used natural flavor compound. Methyl cinnamate (Methyl 3-phenylpropenoate) possesses antimicrobial activity and is a tyrosinase inhibitor that can prevent food browning. Methyl cinnamate (Methyl 3-phenylpropenoate) has antiadipogenic activity through mechanisms mediated, in part, by the CaMKK2-AMPK signaling pathway[1].

  • CAS Number: 103-26-4
  • MF: C10H10O2
  • MW: 162.185
  • Catalog: Bacterial
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 261.9±0.0 °C at 760 mmHg
  • Melting Point: 34-38 °C(lit.)
  • Flash Point: 141.3±9.9 °C

GSK-3β inhibitor 11

GSK-3β inhibitor 11 (compound 21) is a glycogen synthase kinase-3β (GSK-3β) inhibitor (IC50=10.02 μM). GSK-3β inhibitor 11 can be used in neurodegenerative disease research[1].

  • CAS Number: 536731-65-4
  • MF: C20H15N3O4S
  • MW: 393.416
  • Catalog: GSK-3
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Salidroside

Salidroside is a prolyl endopeptidase Inhibitor. Salidroside alleviates cachexia symptoms in mouse models of cancer cachexia via activating mTOR signalling.

  • CAS Number: 10338-51-9
  • MF: C14H20O7
  • MW: 300.304
  • Catalog: mTOR
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 549.5±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 286.2±30.1 °C

Marein

Marein has the neuroprotective effect due to a reduction of damage to mitochondria function and activation of the AMPK signal pathway. Marein improves insulin resistance induced by high glucose in HepG2 cells through CaMKK/AMPK/GLUT1 to promote glucose uptake, through IRS/Akt/GSK-3β to increase glycogen synthesis, and through Akt/FoxO1 to decrease gluconeogenesis. Marein is a HDAC inhibitor with an IC50 of 100 µM. Marein has beneficial antioxidative, antihypertensive, antihyperlipidemic and antidiabetic effects[1][2][3].

  • CAS Number: 535-96-6
  • MF: C21H22O11
  • MW: 450.393
  • Catalog: HDAC
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 835.4±65.0 °C at 760 mmHg
  • Melting Point: 197-202ºC
  • Flash Point: 293.5±27.8 °C

BIP-135

BIP-135 is a potent and selective ATP-competitive GSK-3 inhibitor, with IC50s of 16 nM and 21 nM for GSK-3α and GSK-3β, respectively. BIP 135 exhibits neuroprotective effect[1].

  • CAS Number: 941575-71-9
  • MF: C21H13BrN2O3
  • MW: 421.24400
  • Catalog: GSK-3
  • Density: 1.64±0.1 g/cm3 (20 °C, 760 mmHg)
  • Boiling Point: 643.5±55.0 °C (760 mmHg)
  • Melting Point: N/A
  • Flash Point: N/A

Cbz-B3A

Cbz-B3A is a potent and selective inhibitor of mTORC1 signaling that appear to bind to ubiquilins 1, 2, and 4, and Cbz-B3A inhibits the phosphorylation of eIF4E-binding protein 1 (4EBP1).

  • CAS Number: 1884710-81-9
  • MF: C35H58N6O9
  • MW: 706.87
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AMG 511

AMG 511 is a potent and orally available pan inhibitor of class I PI3Ks, with Kis of 4 nM, 6 nM, 2 nM and 1 nM for PI3Kα, β, δ and γ, respectively. AMG 511 significantly suppresses PI3K signaling that is indicated by p-Akt (Ser473) decrease. AMG 511 exhibits anti-tumor activity in mouse glioblastoma xenograft model[1].

  • CAS Number: 1253573-53-3
  • MF: C22H28FN9O3S
  • MW: 517.58000
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ATR-IN-17

ATR-IN-17 (compound 88) is a potent ATR kinase inhibitor. ATR-IN-17 shows good anticancer activity in LoVo cells, with an IC50 of 1 nM[1].

  • CAS Number: 2761194-15-2
  • MF: C22H28N6O2S
  • MW: 440.56
  • Catalog: ATM/ATR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ATR-IN-7

ATR-IN-7 is a potent inhibitor of ATR. ATR is a class of protein kinases involved in genome stability and DNA damage repair, and is a member of the PIKK family. ATR-IN-7 has the potential for the research of ATR kinase-mediated diseases such as proliferative diseases and cancer (extracted from patent WO2021238999A1, compound 1)[1].

  • CAS Number: 2741917-74-6
  • MF: C21H22FN7O
  • MW: 407.44
  • Catalog: ATM/ATR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI3Kδ-IN-15

PI3Kδ-IN-15 (compound 6b) is a selective PI3Kδ inhibitor with an IC50 of 0.5 nM for p110δ. PI3Kδ-IN-15 inhibits PI3Kδ with >30-fold higher potency than PI3Kγ, PI3Kβ, and PI3Kα[1].

  • CAS Number: 870281-17-7
  • MF: C21H16FN7O
  • MW: 401.40
  • Catalog: PI3K
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MS143

MS143 is a potent AKT degrader (DC50=46 nM and GI50=0.8 µM in PC3 cells). MS143 induces rapid and robust AKT degradation in a concentration- and time-dependent manner via hijacking the ubiquitin-proteasome system. MS143 can suppress cancer cell growth[1].

  • CAS Number: 2376137-41-4
  • MF: C59H81ClN12O6S
  • MW: 1121.87
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ULK1-IN-2

ULK1-IN-2 (compound 3s) is a potent ULK1 inhibitor. ULK1-IN-2 shows highest cytotoxic effect against cancer cell lines, with IC50 of 1.94 μM in A549. ULK1-IN-2 can induce apoptosis and simultaneously block autophagy, and can be used to study NSCLC (Non-small cell lung cancer)[1].

  • CAS Number: 2497409-01-3
  • MF: C19H16BrFN4O6
  • MW: 495.26
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI4KIIIbeta-IN-10

PI4KIIIbeta-IN-10 is a potent PI4KIIIβ inhibitor with an IC50 of 3.6 nM.

  • CAS Number: 1881233-39-1
  • MF: C22H25N3O5S2
  • MW: 475.581
  • Catalog: PI4K
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI3K-IN-37

PI3K-IN-37 (Example 84.1) is a PI3K α/β/δ inhibitor with IC50s of 6, 8, 4 nM, respectively. PI3K-IN-37 can also inhibit mTOR (IC50=4 nM)[1].

  • CAS Number: 1257547-40-2
  • MF: C25H26N6O2
  • MW: 442.51
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A