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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PI3Kδ-IN-11

PI3Kδ-IN-11 is a highly potent and selective PI3Kδ inhibitor with IC50 value of 27.5 nM. PI3Kδ-IN-11 dose-dependently blocks the activity of PI3K/Akt pathway. PI3Kδ-IN-11 can be used for researching B or T cell-related malignancies[1].

  • CAS Number: 2413257-51-7
  • MF: C27H21N5O
  • MW: 431.49
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

22-(4′-py)-JA

22-(4′-py)-JA is a semisynthetic derivative of junamycin A (JA) that can be isolated from the Thai blue sponge (Xestospongia sp.). 22-(4′-py)-JA has antimetastatic activity and can inhibit AKT/mTOR/p70S6K signaling. 22-(4′-py)-JA inhibits tumor cell invasion and tube formation in human umbilical vein endothelial cells (HUVEC), downregulates metalloproteinases (MMP-2 and MMP-9), hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF). 22-(4′-py)-JA has potent anticancer activity against non-small cell lung cancer (NSCLC)[1].

  • CAS Number: 1178895-15-2
  • MF: C32H30N4O8
  • MW: 598.60
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TIC10

TIC10 is a potent, orally active, and stable TRAIL inducer, also inhibits Akt and ERK activity.

  • CAS Number: 1616632-77-9
  • MF: C24H26N4O
  • MW: 386.489
  • Catalog: TNF Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 559.7±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 292.3±32.9 °C

PI3K-IN-34

PI3K-IN-34 (Compound 6g) is a highly selective PI3K inhibitor with IC50 values of 11.73, 6.09 and 11.18 μM for PI3K-α、PI3K-β and PI3K-δ , respectively. PI3K-IN-34 arrests cell cycle at G2/M phase and induces apoptosis. PI3K-IN-34 can be used in leukemia research[1].

  • CAS Number: 2458163-94-3
  • MF: C23H22N6O3
  • MW: 430.46
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

cis,trans-Germacrone

cis,trans-Germacrone is a isomer of Germacrone (HY-N0440). Germacrone exhibits a wide range of antitumor, antioxidant and anti-inflammatory effects. Germacrone inhibits lung cancer cell proliferation and alters the Akt/MDM2/p53. Germacrone also arrests cell cycle at G1/S phase[1].

  • CAS Number: 32663-51-7
  • MF: C15H22O
  • MW: 218.33500
  • Catalog: MDM-2/p53
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CHMFL-PI4K-127

CHMFL-PI4K-127 (compound 15g) is an orally active, potent and high selective PfPI4K (Plasmodium falciparum PI4K kinase) inhibitor, with an IC50 of 0.9 nM. CHMFL-PI4K-127 exhibits potent activity against 3D7 Plasmodium falciparum, with an EC50 of 25.1 nM. CHMFL-PI4K-127 shows antimalaria efficacy[1].

  • CAS Number: 2377604-81-2
  • MF: C18H15ClN4O3S
  • MW: 402.85
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SB216763

SB 216763 is potent, selective and ATP-competitive GSK-3 inhibitor with IC50s of 34.3 nM for both GSK-3α and GSK-3β.

  • CAS Number: 280744-09-4
  • MF: C19H12Cl2N2O2
  • MW: 371.217
  • Catalog: Autophagy
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 598.1±50.0 °C at 760 mmHg
  • Melting Point: 287-288.6ºC(lit.)
  • Flash Point: 315.5±30.1 °C

TG100713

TG 100713 is an inhibitor of PI3K, with IC50s of 24, 50, 165, and 215 nM for PI3Kδ, γ, α and β isoforms respectively[1].

  • CAS Number: 925705-73-3
  • MF: C12H10N6O
  • MW: 254.247
  • Catalog: PI3K
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 646.4±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 344.8±34.3 °C

RP106

Aloisine RP106 (compound 38) is a potent inhibitor of Cdk1/cyclin B, Cdk5/p25, and GSK3 with IC50s of 0.70µM, 1.5µM, 0.92 µM, respectively[1].

  • CAS Number: 496864-15-4
  • MF: C16H17N3O
  • MW: 267.32600
  • Catalog: CDK
  • Density: 1.155g/cm3
  • Boiling Point: N/A
  • Melting Point: 182-184ºC
  • Flash Point: N/A

PI3K/mTOR Inhibitor-2

PI3K/mTOR Inhibitor-2 is a potent dual pan-PI3K/mTOR inhibitor with IC50s of 3.4/34/16/1 nM for PI3Kα/PI3Kβ/PI3Kδ/PI3Kγ and 4.7 nM for mTOR[1]. Antitumor activity[1].

  • CAS Number: 1848242-58-9
  • MF: C20H13ClF2N4O4S
  • MW: 478.86
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L-Leucine-1-13C,15N

L-Leucine-1-13C,15N is the 13C- and 15N-labeled L-Leucine. L-Leucine is an essential branched-chain amino acid (BCAA), which activates the mTOR signaling pathway[1].

  • CAS Number: 80134-83-4
  • MF: C513CH1315NO2
  • MW: 133.15900
  • Catalog: mTOR
  • Density: 1.035 g/cm3
  • Boiling Point: N/A
  • Melting Point: >300ºC(lit.)
  • Flash Point: N/A

SRX3177

SRX3177 is a potent, triple BRD4/PI3K/CDK4/6 inhibitor with nanomolar potency against PI3Kα (IC50=79 nM), BRD4 bromodomains (BD1 and BD2) (IC50=33 nM and 89 nM, respectively), and CDK4/6 (IC50=2.5/3.3 nM).SRX3177 is capable of targeting BRD4, PI3K and CDK4/6 simultaneously, induces apoptosis and cell cycle arrest and has in vitro efficacy in mantle cell lymphoma, hepatocellular carcinoma and neuroblastoma models.SRX3177 has antitumor efficacy in in vivo xenograft models and is less toxic than the combination of agents that inhibit individual targets.

  • CAS Number: 2241237-51-2
  • MF: C31H32N6O4S
  • MW: 584.695
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI3Kδ-IN-13

PI3Kδ-IN-13 (compound 89) is a PI3Kδ inhibitor (IC50=2.6 nM). PI3Kδ-IN-13 can be used in the research of cell proliferation diseases such as cancer, infection, inflammation and autoimmune diseases[1].

  • CAS Number: 1686137-02-9
  • MF: C27H39N7O4S2
  • MW: 589.77
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cazpaullone

Cazpaullone is a glycogen synthase kinase-3 (GSK-3) inhibitor. Cazpaullone can activate pancreatic beta cell protection and replication. Cazpaullone can be used for the research of diabetes[1].

  • CAS Number: 914088-64-5
  • MF: C16H10N4O
  • MW: 274.27700
  • Catalog: GSK-3
  • Density: 1.49±0.1 g/cm3 (20 °C, 760 mmHg)
  • Boiling Point: 680.7±50.0 °C (760 mmHg)
  • Melting Point: N/A
  • Flash Point: N/A

Insulin Detemir

Insulin Detemir is an artificial insulin, shows effect on controlling blood sugar levels. Insulin Detemir stimulates GLP-1 secretion as a consequence of enhanced Gcg expression by a mechanism involving activation of Akt- and/or extracellular signal-regulated kinase (ERK)-dependent-cat and CREB signaling pathways. Insulin Detemir can be used for type 2 diabetes research[1][2].

  • CAS Number: 169148-63-4
  • MF: C267H402N64O76S6
  • MW: 5916.82198
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK2292767

GSK2292767 is a potent and selective inhibitor of PI3Kδ, with a pIC50 of 10.1. GSK2292767 showing greater than 500-fold selective over the other PI3K isoforms. GSK2292767 can be used for the research of respiratory disease[1].

  • CAS Number: 1254036-66-2
  • MF: C24H28N6O5S
  • MW: 512.58100
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

taxamairin B

Taxamairin B is a potent anti-inflammatory agent. Taxamairin B decreases proinflammatory cytokines (TNF-α, IL-1β and IL-6) expression and the production of NO and ROS in LPS-induced RAW264.7 cells. Taxamairin B exhibits significantprotective effects in LPS-induced acute lung injury in mice[1][2].

  • CAS Number: 110300-77-1
  • MF: C22H24O4
  • MW: 352.42400
  • Catalog: Interleukin Related
  • Density: 1.17g/cm3
  • Boiling Point: 577.4ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 252.7ºC

CP-466722

CP-466722 is a rapidly reversible inhibitor of ATM, with an IC50 of 4.1 μM, and has no effects on PI3K or closely related PI3K-like protein kinase (PIKK) family members.

  • CAS Number: 1080622-86-1
  • MF: C17H15N7O2
  • MW: 349.347
  • Catalog: ATM/ATR
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 642.3±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 342.2±34.3 °C

Heterophyllin B

Heterophyllin B is an active cyclic peptide isolated from Pseudostellaria heterophylla. Heterophyllin B provides a novel strategy for the treatment of esophageal cancer[1].

  • CAS Number: 145459-19-4
  • MF: C40H58N8O8
  • MW: 778.937
  • Catalog: PI3K
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 1159.7±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 655.1±34.3 °C

GS-9901

GS-9901 is a highly selective and orally active PI3Kδ inhibitor, with an IC50 of 1 nM. Has potential to treat rheumatoid arthritis[1].

  • CAS Number: 1640247-87-5
  • MF: C22H17ClFN9O
  • MW: 477.88
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Borussertib

Borussertib is a covalent-allosteric and first-in-class inhibitor of protein kinase Akt, with an IC50 of 0.8 nM and a Ki of 2.2 nM for Aktwt[1].

  • CAS Number: 1800070-77-2
  • MF: C36H32N6O3
  • MW: 596.68
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

[1S-(1alpha,2alpha,11balpha)]-1,7,8,11b-tetrahydro-1-hydroxy-2-methoxy-11b-methylcyclopenta[7,8]phenanthro[10,1-bc]furan-3,6,9(2H)-trione

Viridin is a secondary metabolite and naturally occurring furanosteroid. Viridin is potent inhibitor of the lipid kinase PI3K[1][2].

  • CAS Number: 3306-52-3
  • MF: C20H16O6
  • MW: 352.33700
  • Catalog: PI3K
  • Density: 1.51g/cm3
  • Boiling Point: 611.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 323.5ºC

Efortil

Etilefrine hydrochloride is an orally active α adrenergic agonist. Etilefrine hydrochloride is also an AMPK activator. Etilefrine hydrochloride can be used for the research of postural hypotension[1][2][3][4].

  • CAS Number: 943-17-9
  • MF: C10H16ClNO2
  • MW: 217.69
  • Catalog: AMPK
  • Density: 1.127g/cm3
  • Boiling Point: 351.7ºC at 760 mmHg
  • Melting Point: 122ºC
  • Flash Point: 155.5ºC

Aloisine A

Aloisine A (RP107) is a a potent cyclin-dependent kinase (CDK) inhibitor with IC50s of 0.15 μM, 0.12 μM, 0.4 μM, 0.16 μM for CDK1/cyclin B, CDK2/cyclin A, CDK2/cyclin E, CDK5/p35, respectively. Aloisine A ininhibits GSK-3α (IC50=0.5 µM) and GSK-3β (IC50=1.5 µM). Aloisine A stimulates wild-type CFTR and mutated CFTR, with submicromolar affinity by a cAMP-independent mechanism. Aloisine A has the potential for CFTR-related diseases, including cystic fibrosis research[1][2].

  • CAS Number: 496864-16-5
  • MF: C16H17N3O
  • MW: 267.32600
  • Catalog: CDK
  • Density: 1.227g/cm3
  • Boiling Point: N/A
  • Melting Point: 281-283ºC
  • Flash Point: N/A

(R,S)-CHPG

CHPG is a selective mGluR5 agonist, and attenuates SO2-induced oxidative stress and inflammation through TSG-6/NF-κB pathway in BV2 microglial cells[1]. CHPG protects against traumatic brain injury (TBI) in vitro and in vivo by activation of the ERK and Akt signaling pathways[2].

  • CAS Number: 170846-74-9
  • MF: C8H8ClNO3
  • MW: 201.60700
  • Catalog: mGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK-3β inhibitor 14

GSK-3β inhibitor 14 (Compound 6i), benzothiazepinone derivative, is a weak GSK-3β inhibitor (IC50 >100 μM)[1].

  • CAS Number: 863004-48-2
  • MF: C17H17NOS
  • MW: 283.39
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MK-2206

MK-2206 is an orally active, highly potent and selective allosteric Akt inhibitor, with IC50s of 8, 12, and 65 nM for Akt1, Akt2, and Akt3, respectively. Many breast cancer cell lines, and PIK3CA-mutant and cell lines with PTEN loss are sensitive to MK-2206. Anticancer activities[1][2].

  • CAS Number: 1032349-77-1
  • MF: C25H22ClN5O
  • MW: 443.92800
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

2-Chlorophenoxazine

2-Chlorophenoxazine is a Akt inhibitor with an IC50 value of 2-5 μM for in vitro. 2-Chlorophenoxazine can induce apoptosis.2-Chlorophenoxazine can be used for cancer diseases research[1].

  • CAS Number: 56821-03-5
  • MF: C12H8ClNO
  • MW: 217.65
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Chamaejasmine

Chamaejasmine is a biflavonoid that can be isolated from the roots of Stellera chamaejasme L. Chamaejasmine has antitumor activity. Chamaejasmine induces cell Apoptosis, Autophagy and ROS production, and activates the activity of AMPK/mTOR signal pathway[1].

  • CAS Number: 69618-96-8
  • MF: C30H22O10
  • MW: 542.49000
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DNA-PK-IN-2

DNA-PK-IN-2 is a potent inhibitor of DNA-PK. DNA-dependent protein kinase (DNA-PK) is a DNA-PK enzyme complex composed of Ku70/Ku80 heterodimer and DNA-dependent protein kinase catalytic subunit (DNA-PKcs). DNA-PK-IN-2 has the potential for the research of cancer diseases (extracted from patent WO2021136462A1, compound 1)[1].

  • CAS Number: 2665720-22-7
  • MF: C20H23N5O3
  • MW: 381.43
  • Catalog: DNA-PK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A