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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Akt Inhibitor IV

Akt inhibitor-IV (AKTIV) acts as a PI3K-Akt inhibitor at the E isomer (HY-14971), with potent cytotoxicity[1].

  • CAS Number: 681281-88-9
  • MF: C31H27IN4S
  • MW: 614.54
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Alpelisib hydrochloride

Alpelisib hydrochloride (BYL-719 hydrochloride) is a potent and selective PI3Kα inhibitor with IC50s of 5 nM, 250 nM, 290 nM and 1200 nM for p110α, p110γ, p110δ, and p110β, respectively[1].

  • CAS Number: 1584128-91-5
  • MF: C19H23ClF3N5O2S
  • MW: 477.93
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ATR-IN-16

ATR-IN-16 (compound 46) is a potent ATR kinase inhibitor. ATR-IN-16 shows good anticancer activity in LoVo cells, with an IC50 of 410 nM[1].

  • CAS Number: 2756589-62-3
  • MF: C19H25N7O
  • MW: 367.45
  • Catalog: ATM/ATR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

D-α-Hydroxyglutaric acid

D-α-Hydroxyglutaric acid ((R)-2-Hydroxypentanedioic acid) is the principal metabolite accumulating in neurometabolic disease D-2-hydroxyglutaric aciduria. D-α-Hydroxyglutaric acid is a weak competitive antagonist of α-ketoglutarate (α-KG) and inhibits multiple α-KG-dependent dioxygenases with a Ki of 10.87 mM. D-α-Hydroxyglutaric acid increases reactive oxygen species (ROS) production. D-α-Hydroxyglutaric acid binds and inhibits ATP synthase and inhibits mTOR signaling[1][2][3][4][5].

  • CAS Number: 13095-47-1
  • MF: C5H8O5
  • MW: 148.11400
  • Catalog: ATP Synthase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TMBIM6 antagonist-1

TMBIM6 antagonist-1, a potential TMBIM6 antagonist, prevents TMBIM6 binding to mTORC2, decreases mTORC2 activity, and also regulates TMBIM6-leaky Ca2+[1].

  • CAS Number: 123134-61-2
  • MF: C15H12N2O3
  • MW: 268.267383575439
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI3K/mTOR Inhibitor-13 sodium

PI3K/mTOR Inhibitor-13 sodium is an orally active dual inhibitor of phosphoinositol 3-kinase (PI3K) and mTOR kinase. PI3K/mTOR Inhibitor-13 sodium has potential applications in sexual diseases, solid tumor and idiopathic pulmonary fibrosis (IPF)[1][2].

  • CAS Number: 2361009-23-4
  • MF: C20H13F2N5NaO3S
  • MW: 464.40
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sennidin B

Sennidin B, a stereoisomer isolated from the leaves of Cassia angustifolia, has lower activity than Sennidin A. Sennidin A inhibits HCV NS3 helicase, with an IC50 of 0.8 μM. Sennidin A induces phosphorylation of Akt and glucose transporter 4 (GLUT4) translocation. Sennidin A stimulates the glucose incorporation [1][2].

  • CAS Number: 517-44-2
  • MF: C30H18O10
  • MW: 538.458
  • Catalog: HCV
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 801.8±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 452.6±30.8 °C

AMPK activator 11

AMPK activator 11 is an AMP-activated protein kinase (AMPK) activator with nanomolelevel antiproliferation activities against several CRCs. AMPK activator 11 selectively inhibits the RKO xenograft growth along by activating AMPK and upregulating oxidative phosphorylation (OXPHOS) ( mitochondrial metabolism ) and can be used for anti-tumor and metabolic disease research[1].

  • CAS Number: 2948304-00-3
  • MF: C25H20N4O2
  • MW: 408.45
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

12-Hydroxyabieta-8,12-diene-11,14-dione

Royleanone, a diterpenoid isolated from plants, inhibits the proliferation of cancer cells by inducing cell cycle arrest and mitochondria-mediated apoptosis, also inhibits cell migration potential, inhibits mTOR/PI3/AKT signaling pathway in LNCaP prostate cancer cells[1].

  • CAS Number: 6812-87-9
  • MF: C20H28O3
  • MW: 316.43
  • Catalog: Akt
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 426.4±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 225.8±25.2 °C

AZD-0156

AZD0156 is an oral, potent and selective ATM inhibitor with an IC50 of 0.58 nM.

  • CAS Number: 1821428-35-6
  • MF: C26H31N5O3
  • MW: 461.556
  • Catalog: ATM/ATR
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 628.3±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 333.8±31.5 °C

PI3K/mTOR Inhibitor-1

PI3K/mTOR Inhibitor-1 is a potent, orally bioavailable dual PI3K/mTOR inhibitor with IC50s of 20/376/204/46 nM and 186 nM for PI3Kα/PI3Kβ/PI3Kγ/PI3Kδ and mTOR, respectively[1]. Antitumor activity[1].

  • CAS Number: 1949802-49-6
  • MF: C18H22FN5O3S
  • MW: 407.46
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

YH-306

YH-306 is a candidate drug in preventing growth and metastasis of colorectal cancer by modulating FAK signalling pathway.

  • CAS Number: 1373764-75-0
  • MF: C19H18N2O2
  • MW: 306.36
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HL-8

HL-8 is a PROTAC molecule targeting PI3K kinase. HL-8 has a significant and complete degradation effect on PI3K kinase at a concentration of 10 μM within 8 h. HL-8 has the potential for the research of cancer diseases[1].

  • CAS Number: 2766352-64-9
  • MF: C57H59F2N11O9S2
  • MW: 1144.27
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Demethylasterriquinone B1

Demethylasterriquinone B1 is a selective insulin receptor activator. Demethylasterriquinone B1 stimulates tyrosine phosphorylation of the IR β subunit, and the activation of PIK3 and AKT[1].

  • CAS Number: 78860-34-1
  • MF: C32H30N2O4
  • MW: 506.59200
  • Catalog: Akt
  • Density: 1.335g/cm3
  • Boiling Point: 780.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 425.6ºC

7-Methoxyisoflavone

7-Methoxyisoflavone is an isoflavone derivative and also an activator of adenosine monophosphate-activated protein kinase (AMPK).

  • CAS Number: 1621-56-3
  • MF: C16H12O3
  • MW: 252.26500
  • Catalog: AMPK
  • Density: 1.24g/cm3
  • Boiling Point: 421.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 200.3ºC

Aschantin

Aschantin, a bisepoxylignan, can be isolated from Magnolia biondii. Aschantin has antiplasmodial, Ca2+-antagonistic, platelet activating factor-antagonistic, and chemopreventive activities. Aschantin is a mTOR kinase inhibitor. Aschantin is also an inhibitor of Cytochrome P450 and UGT enzyme[1][2].

  • CAS Number: 13060-15-6
  • MF: C22H24O7
  • MW: 400.42
  • Catalog: Cytochrome P450
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 525.8±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 214.7±30.0 °C

Akt-I-1,2 HCl

AKT-IN-20 is an AKT inhibitor, and can be used for research of cancer[1]

  • CAS Number: 473382-50-2
  • MF: C23H22ClN3
  • MW: 375.89400
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CAY10404

CAY10404 is a potent and highly selective cyclooxygenase-2 (COX-2) inhibitor with an IC50 of 1 nM. CAY10404 exhibits no inhibition of COX-1 (IC50>500 µM)[1]. CAY10404 is a potent inhibitor of PKB/Akt and MAPK signaling pathways and induces apoptosis in NSCLC cells. CAY10404, a diarylisoxazole, has good analgesic, anti-inflammatory, and anti-cancer activities[2][3].

  • CAS Number: 340267-36-9
  • MF: C17H12F3NO3S
  • MW: 367.342
  • Catalog: Apoptosis
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 498.6±45.0 °C at 760 mmHg
  • Melting Point: 196.47 °C(Predicted)
  • Flash Point: 255.3±28.7 °C

PI3Kα-IN-13

PI3Kα-IN-13 (Compound 18a) is a PI3Kα inhibitor (IC50: 2.5 nM). PI3Kα-IN-13 induces tumor cell apoptosis. PI3Kα-IN-13 inhibits cancer cell proliferation with IC50s of 0.75 μM (MCF-7), 3.79 μM (HCT-116), 13.71 μM (MDA-MB-231), 9.85 μM (SW620), respectively. PI3Kα-IN-13 inhibits tumor cell colony formation, migration and invasion[1].

  • CAS Number: 2955529-67-4
  • MF: C21H19N5O3
  • MW: 389.41
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Exisulind

Sulindac sulfone is an mTORC1 pathway inhibitor and a metabolite of Sulindac. Sulindac sulfone inhibits colon cancer cell growth and induces cell cycle arrest. Sulindac sulfone is used in cancer research[1].

  • CAS Number: 59973-80-7
  • MF: C20H17FO4S
  • MW: 372.41
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 248-250ºC
  • Flash Point: N/A

OTSSP167 hydrochloride

OTSSP167 (hydrochloride) is a highly potent MELK inhibitor with IC50 value of 0.41 nM.

  • CAS Number: 1431698-10-0
  • MF: C25H29Cl3N4O2
  • MW: 523.882
  • Catalog: MELK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PfGSK3/PfPK6-IN-2

PfGSK3/PfPK6-IN-2 is a potent dual PfGSK3/PfPK6 (Plasmodium falciparum GSK3/PK6) inhibitor (IC50: 172 nM and 11 nM respectively). PfGSK3/PfPK6-IN-2 can be used in the research of Malaria[1].

  • CAS Number: 2797225-47-7
  • MF: C24H25Cl2N5OS
  • MW: 502.46
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

rac-AZD 6482

rac-AZD 6482 (rac-KIN-193) is a less active racemate of AZD 6482. AZD 6482 is a potent and selective p110β inhibitor with an IC50 of 0.69 nM.

  • CAS Number: 663620-70-0
  • MF: C22H24N4O4
  • MW: 408.45000
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PRE-084 hydrochloride

PRE-084 is a highly selective σ1 receptor (S1R) agonist, with an IC50 of 44 nM. PRE-084 exhibits good neuroprotective effects, can improve motor function and motor neuron survival in mice. PRE-084 also can ameliorate myocardial ischemia-reperfusion injury in rats by activating the Akt-eNOS pathway[1][2][3][4].

  • CAS Number: 138847-85-5
  • MF: C19H27NO3
  • MW: 317.42
  • Catalog: Sigma Receptor
  • Density: 1.103g/cm3
  • Boiling Point: 446.6ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 223.9ºC

PI3K/mTOR Inhibitor-7

PI3K/mTOR Inhibitor-7 (Compound 19i) is a potent and dual inhibitor of PI3K/mTOR. PI3K/mTOR Inhibitor-7 shows 4.7-fold higher potency than the positive control gedatolisib (0.3 vs. 1.4 μM, IC50 values). PI3K/mTOR Inhibitor-7 significantly suppresses the PI3K/Akt/mTOR signaling pathway at 10 μM. PI3K/mTOR Inhibitor-7 has the potential for the research of cancer diseases[1].

  • CAS Number: 2456295-65-9
  • MF: C29H33N9O4
  • MW: 571.63
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI3Kγ inhibitor 6

PI3Kγ inhibitor 6 (compound 9) is a PI3Kγ inhibitor. PI3Kγ inhibitor 6 can be used for the research of inflammatory and autoimmune diseases[1].

  • CAS Number: 900515-01-7
  • MF: C16H11NO5S
  • MW: 329.32724
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CHMFL-PI3KD-317

CHMFL-PI3KD-317 is a highly potent, selective and orally active PI3Kδ inhibitor, with an IC50s of 6 nM, and exhibits over 10-1500 fold selectivity over other class I, II and III PIKK family isoforms, such as PI3Kα (IC50, 62.6 nM), PI3Kβ (IC50, 284 nM), PI3Kγ (IC50, 202.7 nM), PIK3C2A (IC50, >10000 nM), PIK3C2B (IC50, 882.3 nM), VPS34 (IC50, 1801.7 nM), PI4KIIIA (IC50, 574.1 nM) and PI4KIIIB (IC50, 300.2 nM). CHMFL-PI3KD-317 inhibits PI3Kδ-mediated Akt T308 phosphorylation in Raji cells, with an EC50 of 4.3 nM. CHMFL-PI3KD-317 has antiproliferative effects on cancer cells[1].

  • CAS Number: 2244992-76-3
  • MF: C21H24ClN5O3S2
  • MW: 494.03
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI3K/mTOR Inhibitor-8

PI3K/mTOR Inhibitor-8 (Compound 18b) is a PI3K and mTOR dual inhibitor with IC50 values of 0.46 nM and 12 nM against PI3Kα and mTOR, respectively. PI3K/mTOR Inhibitor-8 induces HCT-116 cells apoptosis and arrests cell cycle at the G1/S phase[1].

  • CAS Number: 2492376-85-7
  • MF: C23H22N8O4S
  • MW: 506.54
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TAT-TCL1-Akt-in

TAT-TCL1-Akt-in is an Akt inhibitor[1].

  • CAS Number: 1073630-46-2
  • MF: C152H239N55O36
  • MW: 3412.87
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Akt1&PKA-IN-1

Akt1&PKA-IN-1 is a potent dual Akt/PKA inhibitor with IC50 values of 0.03 , 0.11 μM, and 9.8 μM for PKAa, Akt, and CDK2, respectively. Akt1&PKA-IN-1 is selective for cyclin-dependent kinase 2 (CDK2)[1].

  • CAS Number: 1334107-58-2
  • MF: C20H17Cl2N3O
  • MW: 386.27
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A