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-IN-9

AKT-IN-9 is a potent inhibitor of AKT. Protein kinase B (PKB, also known as AKT) is central to PI3K/AKT/mTOR signaling in cells, and its function is important for cell growth, survival, differentiation and metabolism. AKT-IN-9 has the potential for the research of breast and prostate cancer (extracted from patent WO2021185238A1, compound 1)[1].

  • CAS Number: 2709045-53-2
  • MF: C24H29ClN6O
  • MW: 452.98
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Torkinib (PP242)

Torkinib (PP 242) is a selective and ATP-competitive mTOR inhibitor with an IC50 of 8 nM. PP242 inhibits both mTORC1 and mTORC2 with IC50s of 30 nM and 58 nM, respectively.

  • CAS Number: 1092351-67-1
  • MF: C16H16N6O
  • MW: 308.338
  • Catalog: Autophagy
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 642.0±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 342.1±30.1 °C

Coelonin

Coelonin is a dihydrophenanthrene with anti-inflammation activity. Coelonin inhibits LPS-induced PTEN phosphorylation. Coelonin inhibits NF-κB activation and p27Kip1 degradation by regulating the PI3K/AKT pathway negatively. Coelonin can inhibit IκBα phosphorylation and degradation and increases the expression of IκBα protein[1][2].

  • CAS Number: 82344-82-9
  • MF: C15H14O3
  • MW: 242.27000
  • Catalog: Interleukin Related
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BRD3731

BRD3731 is a selective GSK3β inhibitor, with IC50s of 15 nM and 215 nM for GSK3β and GSK3α, respectively. BRD3731 can be used for the research of a mood disorder, post-traumatic stress disorder (PTSD), psychiatric disorder, diabetes, and neurodegenerative disorder[1].

  • CAS Number: 2056262-07-6
  • MF: C24H31N3O
  • MW: 377.52
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NVP-CLR457

NVP-CLR457 (compound 40) is an orally active, potent and balanced pan-class I PI3K inhibitor. NVP-CLR457 shows a clear dose-dependent PK/PD/efficacy relationship. NVP-CLR457 has antitumor activity[1].

  • CAS Number: 1453082-52-4
  • MF: C18H20F3N7O4
  • MW: 455.39
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

A-443654

A-443654 is a potent Akt1/2/3 inhbitor, with a Ki of 160 pM for Akt1.

  • CAS Number: 552325-16-3
  • MF: C24H23N5O
  • MW: 397.472
  • Catalog: Akt
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 722.0±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 390.4±32.9 °C

RGB-286638

RGB-286638 is a CDK inhibitor that inhibits the kinase activity of cyclin T1-CDK9, cyclin B1-CDK1, cyclin E-CDK2, cyclin D1-CDK4, cyclin E-CDK3, and p35-CDK5 with IC50s of 1, 2, 3, 4, 5 and 5 nM, respectively; also inhibits GSK-3β, TAK1, Jak2 and MEK1, with IC50s of 3, 5, 50, and 54 nM.

  • CAS Number: 784210-88-4
  • MF: C29H35N7O4
  • MW: 545.633
  • Catalog: MEK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RMC-4627

RMC-4627 is a selective mTORC1 inhibitor that activates 4EBP1 and inhibits tumor growth.

  • CAS Number: 2250059-52-8
  • MF: C93H141N11O23
  • MW: 1781.17
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ATM Inhibitor-6

ATM inhibitor-6 (A-193) is a selective ATM kinase inhibitor. ATM inhibitor-6 can be used in cancer research[1].

  • CAS Number: 2765544-85-0
  • MF: C28H33FN6O2
  • MW: 504.60
  • Catalog: ATM/ATR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AT-533

AT-533 is a potent Hsp90 and HSV inhibitor. AT-533 suppresses tumor growth and angiogenesis by blocking the HIF-1α/VEGF/VEGFR-2 signaling pathway. AT-533 also inhibits the activation of the downstream pathways, including Akt/mTOR/p70S6K, Erk1/2 and FAK. AT-533 inhibits the tube formation, cell migration, and invasion of human umbilical vein endothelial cells (HUVECs)[1][2][3].

  • CAS Number: 908112-37-8
  • MF: C23H30N4O3
  • MW: 410.51
  • Catalog: HSV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DNA-PK-IN-10

DNA-PK-IN-10 is a DNA-PK inhibitor. DNA-PK-IN-10 can be used for the research of breast cancer and non-small cell lung cancer[1].

  • CAS Number: 2919315-89-0
  • MF: C25H28N6O2
  • MW: 444.53
  • Catalog: DNA-PK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Platycodin D

Platycodin D is a saponin isolated from Platycodi Radix, acts as an activator of AMPKα, with anti-obesity property[1].

  • CAS Number: 58479-68-8
  • MF: C57H92O28
  • MW: 1225.324
  • Catalog: AMPK
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BAY 80-6946 (Copanlisib)

Copanlisib (BAY 80-6946) is a selective and ATP-competitive class-I PI3 kinases inhibitor, with IC50s of 0.5, 0.7, 3.7 and 6.4 nM for PI3Kα, PI3Kδ, PI3Kβ and PI3Kγ, respectively.

  • CAS Number: 1032568-63-0
  • MF: C23H28N8O4
  • MW: 480.520
  • Catalog: PI3K
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KDU731

KDU731, an orally active C. parvum PI4K inhibitor with an IC50 value of 25 nM, blocks Cryptosporidium infection in vitro and in vivo[1][2]. KDU731 is a promising drug candidate for the treatment of diarrhea caused by Cryptosporidium and meets a broad range of safety[2].

  • CAS Number: 1610610-48-4
  • MF: C22H16N6O2
  • MW: 396.40
  • Catalog: Parasite
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BX517

BX517 is a potent and selective inhibitor of PDK1 with IC50 of 6 nM.

  • CAS Number: 850717-64-5
  • MF: C15H14N4O2
  • MW: 282.29700
  • Catalog: PDK-1
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Indirubin-5-sulfonate

Indirubin-5-sulfonate is a cyclin-dependent kinase (CDK) inhibitor, with IC50 values of 55 nM, 35 nM, 150 nM, 300 nM and 65 nM for CDK1/cyclin B, CDK2/cyclin A, CDK2/cyclin E, CDK4/cyclin D1, and CDK5/p35, respectively[1]. Indirubin-5-sulfonate also shows inhibitory activity against GSK-3β[2].

  • CAS Number: 244021-67-8
  • MF: C16H10N2O5S
  • MW: 342.33
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Uprosertib

Uprosertib (GSK2141795) is a potent and selective pan-Akt inhibitor with IC50 values of 180/328/38 nM for Akt1/Akt2/Akt3, respectively.

  • CAS Number: 1047634-65-0
  • MF: C18H16Cl2F2N4O2
  • MW: 429.24800
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AKT-IN-10

AKT-IN-10 is a potent inhibitor of AKT. Protein kinase B (PKB, also known as AKT) is central to PI3K/AKT/mTOR signaling in cells, and its function is important for cell growth, survival, differentiation and metabolism. AKT-IN-10 has the potential for the research of breast and prostate cancer (extracted from patent WO2021185238A1, compound 4)[1].

  • CAS Number: 2709045-56-5
  • MF: C26H34ClN5O2
  • MW: 484.03
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ATR-IN-15

ATR-IN-15 (compound 1) is an orally active and potent ATR kinase inhibitor, with an IC50 of 8 nM. ATR-IN-15 also inhibits human colon tumor cells LoVo, DNA-PK and PI3K, with IC50 values of 47, 663 and 5131 nM, respectively[1].

  • CAS Number: 2756665-52-6
  • MF: C19H22N8O
  • MW: 378.43
  • Catalog: ATM/ATR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2-(3,4-Dihydroxy-benzylidene)-benzofuran-3-one,Sphingosine Kinase Inhibitor V

SKI V is a noncompetitive and potent non-lipid sphingosine kinase (SPHK; SK) inhibitor with an IC50 of 2 μM for GST-hSK. SKI V potently inhibits PI3K with an IC50 of 6 μM for hPI3k. SKI V decreases formation of the mitogenic second messenger sphingosine-1-phosphate (S1P). SKI V induces apoptosis and has antitumor activity[1][2].

  • CAS Number: 24418-86-8
  • MF: C15H10O4
  • MW: 254.24
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(1r,4r)-4-(((6-(1-(Cyclopropylmethyl)-2-oxo-1,2-dihydropyridin-4-yl)benzo[d]thiazol-2-yl)amino)methyl)cyclohexane-1-carboxylicacid

PI4K-IN-1 (compound 44) is a potent PI4KIII inhibitor, with pIC50 values of 9.0 and 6.6 for PI4KIIIα and PI4KIIIβ, respectively. PI4K-IN-1 also inhibits PI3Kα/β/γ/δ, with pIC50 values of 4.0/<3.7/5.0/<4.1, respectively[1].

  • CAS Number: 1800017-49-5
  • MF: C24H27N3O3S
  • MW: 437.55
  • Catalog: PI3K
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 690.9±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 371.6±34.3 °C

VO-OHpic

VO-OHPic is a reversible, noncompetitive and selective PTEN inhibitor with an IC50 of 46 nM. VO-OHPic attenuates apoptosis, adverse cardiac remodeling, and pro-inflammatory M1 macrophages in doxorubicin-induced cardiomyopathy. VO-OHPic inhibits autophagy[1][2][3].

  • CAS Number: 675848-25-6
  • MF: C12H10N2O8V
  • MW: 361.16
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MSC2360844

MSC2360844 is a potent, orally active and selective PI3Kδ inhibitor, with an IC50 of 145 nM. MSC2360844 shows highly selective against a panel of 278 additional kinases[1].

  • CAS Number: 1305267-37-1
  • MF: C26H27FN4O5S
  • MW: 526.58
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NSC45586 free base

NSC45586 free base (NCS 45586, NCI45586) is a potent, specific PHLPP2 inhibitor with IC50 of 4 uM, targets the PHLPP2 PP2C domain, suppresses MYC and triggers cell death.

  • CAS Number: 739301-85-0
  • MF: C20H18N6O3
  • MW: 390.403
  • Catalog: Ser/Thr Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Monomethyl lithospermate

Monomethyl lithospermate activates the PI3K/AKT pathway, which plays a protective role in nerve injury. Monomethyl lithospermate can improve the survival ability of SHSY-5Y cells, inhibit the breakdown of mitochondrial membrane potential (MMOP) and inhibit cell apoptosis. Monomethyl lithospermate also reduced the level of oxidative stress in the brain tissue of rats with middle artery occlusion (MCAO) and improved nerve damage in rats with ischemic stroke (IS)[1].

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

6-Gingerol

[6]-Gingerol is an active compound isolated from Ginger (Zingiber officinale Rosc), exhibits a variety of biological activities including anticancer, anti-inflammation, and anti-oxidation.

  • CAS Number: 23513-14-6
  • MF: C17H26O4
  • MW: 294.386
  • Catalog: Apoptosis
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 453.0±35.0 °C at 760 mmHg
  • Melting Point: 30 - 32ºC
  • Flash Point: 159.0±19.4 °C

Indirubin-3'-monoxime-5-sulphonic acid

Indirubin-3'-monoxime-5-sulphonic acid is a potent and selective inhibitor of CDK1, CDK5, and GSK-3β with IC50s of 5 nM, 7 nM, and 80 nM, respectively[1].

  • CAS Number: 331467-05-1
  • MF: C16H11N3O5S
  • MW: 357.34
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AKT-IN-8

AKT-IN-8 is a potent AKT inhibitor with IC50s of 4.46, 2.44, and 9.47 nM for AKT1, AKT2, and AKT3, respectively[1].

  • CAS Number: 2654026-13-6
  • MF: C22H25ClN6O3
  • MW: 456.93
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI3K-IN-28

PI3K-IN-28 (Compound 6c) is a potent inhibitor of PI3K. PI3K-IN-28 displays the most potent activity with lower toxic effects on MCF-10a. PI3K-IN-28 displays half-maximal inhibitory concentration (IC50, μM) values of 5.8, 2.3, and 7.9. PI3K-IN-28 is the most potent one with a selectivity index (SI) of 39 and is considered as a latent lead for further optimization of anticancer agents[1].

  • CAS Number: 2747100-02-1
  • MF: C26H16F9N3O3S2
  • MW: 653.54
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tideglusib

Tideglusib is an irreversible GSK-3 inhibitor with IC50s of 5 nM and 60 nM for GSK-3βWT (1 h preincubation) and GSK-3βC199A (1 h preincubation), respectively.

  • CAS Number: 865854-05-3
  • MF: C19H14N2O2S
  • MW: 334.392
  • Catalog: GSK-3
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 511.3±43.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 263.0±28.2 °C