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-2

AKT-IN-2 is a potent, selective and orally bioavailable AKT inhibitor with an IC50 of 5 nM for AKT1[1].

  • CAS Number: 1295514-91-8
  • MF: C25H34F3N7O
  • MW: 505.58
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

iMDK

iMDK is a small molecule inhibitor of the growth factor Midkine (MDK) that suppresses the endogenous expression of MDK but not other growth factors such as PTN or VEGF; inhibits the cell growth of MDK-positive H441 lung adenocarcinoma cells that harbor an oncogenic KRAS mutation and H520 squamous cell lung cancer cells, inhibits PI3K pathway and induces apoptosis; significantly inhibits tumor growth in a xenograft mouse model in vivo.

  • CAS Number: 881970-80-5
  • MF: C21H13FN2O2S
  • MW: 376.404
  • Catalog: PI3K
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(32-Carbonyl)-RMC-5552

(32-Carbonyl)-RMC-5552 is a potent mTOR inhibitor. (32-Carbonyl)-RMC-5552 inhibits mTORC1 and mTORC2 substrate (p-P70S6K-(T389), p-4E-BP1-(T37/36), AND p-AKT1/2/3-(S473)) phosphorylation with pIC50s of > 9, >9 and between 8 and 9, respectively (patent WO2019212990A1, example 2)[1].

  • CAS Number: 2382768-55-8
  • MF: C93H134N10O24
  • MW: 1776.11
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Torin 1

Torin 1 is a potent inhibitor of mTOR with an IC50 of 3 nM. Torin 1 inhibits both mTORC1/2 complexes with IC50 values between 2 and 10 nM.

  • CAS Number: 1222998-36-8
  • MF: C35H28F3N5O2
  • MW: 607.624
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 817.2±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 448.0±34.3 °C

TC-G 24

TC-G 24 (Compound 24) is a potent, selective glycogen synthase kinase-3β (GSK-3β) inhibitor with an IC50 of 17.1 nM. TC-G 24 can cross the BBB and can be used for studying many diseases such as type 2 diabetes mellitus, stroke, Alzheimer, and other related diseases[1].

  • CAS Number: 1257256-44-2
  • MF: C15H11ClN4O3
  • MW: 330.73
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Keramamine A

Manzamine A, an orally active beta-carboline alkaloid, inhibits specifically GSK-3β and CDK-5 with IC50s of 10.2 μM and 1.5 μM, respectively. Manzamine A targets vacuolar ATPases and inhibits Autophagy in pancreatic cancer cells. Manzamine A has antimalarial and anticancer activities. Manzamine A also shows potent activity against HSV-1[1][2][3][4].

  • CAS Number: 104196-68-1
  • MF: C36H44N4O
  • MW: 548.76100
  • Catalog: HSV
  • Density: 1.26g/cm3
  • Boiling Point: 756.6ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 411.4ºC

PI3Kγ inhibitor 4

PI3Kγ inhibitor 4 is a potent, selective and orally active inhibitor of PI3Kγ, with an IC50 of 40 nM. PI3Kγ inhibitor 4 shows ∼7, 43, and 18-fold selectivity for PI3Kγ over the α, β, and δ isoforms, respectively. PI3Kγ inhibitor 4 can be used for the research of airway inflammation[1].

  • CAS Number: 1821038-80-5
  • MF: C20H24N4O4S
  • MW: 416.49
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

l-leucine-d7

L-Leucine-d7 is the deuterium labeled L-Leucine. L-Leucine is an essential branched-chain amino acid (BCAA), which activates the mTOR signaling pathway[1].

  • CAS Number: 92751-17-2
  • MF: C6H6D7NO2
  • MW: 138.21600
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: >300ºC(lit.)
  • Flash Point: N/A

P-2281

P-2281 is a mTOR inhibitor with the activity of improving colitis.

  • CAS Number: 1112994-35-0
  • MF: C9H8ClN3O
  • MW: 209.63
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3-Methylthienyl-carbonyl-JNJ-7706621

3-Methylthienyl-carbonyl-JNJ-7706621 is a potent and selective inhibitor of cyclin-dependent kinase (CDK), with IC50s of 6.4 nM and 2 nM for CDK1/cyclin B and CDK2/cyclin A, respectively. 3-Methylthienyl-carbonyl-JNJ-7706621 also shows potent inhibition of GSK-3 (IC50=0.041 μM) and modest potency against CDK4, VEGF-R2, and FGF-R2 (IC50=0.11, 0.13, 0.22 μM, respectively). 3-Methylthienyl-carbonyl-JNJ-7706621 can be used for the research of cancer[1].

  • CAS Number: 443798-09-2
  • MF: C14H14N6O3S2
  • MW: 378.43
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CHIR 98014

CHIR 98024 (Compound L) is a glycogen synthase kinase 3 (GSK3) inhibitor with an EC50 of 0.2566 μM[1].

  • CAS Number: 556813-39-9
  • MF: C20H17Cl2N9O2
  • MW: 486.314
  • Catalog: GSK-3
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 839.0±75.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 461.2±37.1 °C

VPS34 inhibitor 1 (Compound 19, PIK-III analogue)

Vps34-IN-4 (compound 19) is a potent, selective, and orally active inhibitor of VPS34. Vps34-IN-4 inhibits the autophagy in vivo. Autophagy is a dynamic process that regulates lysosomal-dependent degradation of cellular components[1].

  • CAS Number: 1383716-46-8
  • MF: C21H25N7O
  • MW: 391.47
  • Catalog: Autophagy
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 676.1±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 362.7±34.3 °C

MMP-9-IN-5

MMP-9-IN-5 is a MMP-9 inhibitor (IC50: 4.49 nM) that forms hydrogen bond with MMP-9. MMP-9-IN-5 also inhibits AKT activity (IC50: 1.34 nM). MMP-9-IN-5 shows cell cytotoxicity and induces cell apoptosis. MMP-9-IN-5 can be used in the research of cancers[1].

  • CAS Number: 2581824-80-6
  • MF: C27H20IN3O4
  • MW: 577.37
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PKD-IN-1 dihydrochloride

PKD-IN-1 dihydrochloride (compound 32), an aminoethylamino-aryl (AEAA) compound, acts as PKD-1 inhibitor. PKD-IN-1 can be used for protein kinase D (PKD)-mediated diseases research[1].

  • CAS Number: 2308510-39-4
  • MF: C18H21N4OCl3
  • MW: 415.74
  • Catalog: PDK-1
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

eCF-309

eCF309 is a potent and highly selective mTOR inhibitor with remarkably low off-target activities (IC50 = 10-15 nM, both in vitro and in cells)[1].

  • CAS Number: 2001571-40-8
  • MF: C18H21N7O3
  • MW: 383.404
  • Catalog: mTOR
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 642.5±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 342.4±34.3 °C

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

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

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

MS170

MS170 is a potent and selective PROTAC AKT degrader. MS170 depletes cellular total AKT (T-AKT) with the DC50 value of 32 nM. MS170 binds to AKT1, AKT2, and AKT3 with Kds of 1.3 nM, 77 nM, and 6.5 nM, respectively[1].

  • CAS Number: 2376136-61-5
  • MF: C45H56ClN9O7
  • MW: 870.44
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Metformin D6 hydrochloride

Metformin D6 hydrochloride is a deuterium labeled Metformin hydrochloride. Metformin hydrochloride inhibits the mitochondrial respiratory chain in the liver, leading to activation of AMPK, enhancing insulin sensitivity for type 2 diabetes research. Metformin hydrochloride triggers autophagy[1].

  • CAS Number: 1185166-01-1
  • MF: C4H6D6ClN5
  • MW: 171.662
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 215-218°C
  • Flash Point: N/A

PIMPC

PIMPC is a compound with antioxidant and metal-chelating properties. PIMPC is a novel inhibitor of glycogen synthase kinase 3 (GSK-3). PIMPC has potential anti-Alzheimer's disease effect[1].

  • CAS Number: 2250244-44-9
  • MF: C21H19N5O
  • MW: 357.41
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sophocarpine

Sophocarpine is one of the significant alkaloid extracted from the traditional herb medicine Sophora flavescens which has many pharmacological properties such as anti-virus, anti-tumor, anti-inflammatory. Sophocarpine significantly inhibits the growth of gastric cancer (GC) cells through multiple mechanisms such as induction of autophagy, activation of cell apoptosis and down-regulation of cell survival PI3K/AKT signaling pathway. Sophocarpine has been demonstrated to have anti-tumor activity in various cancer cells, including hepatocellular carcinoma, prostate cancer and colorectal cancer[1].

  • CAS Number: 6483-15-4
  • MF: C15H22N2O
  • MW: 246.348
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 425.4±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 194.0±21.1 °C

PI3Kδ-IN-1

PI3Kδ-IN-1 is a potent, selective, and efficacious PI3Kδ inhibitor with an IC50 of 1.7 nM.

  • CAS Number: 1911564-39-0
  • MF: C22H20F3N7O2
  • MW: 471.44
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SB 203580 hydrochloride

SB 203580 hydrochloride is a widely used p38 MAPK inhibitor with an IC50 of 0.3-0.5 μM. It shows more than 100-fold selectivity over PKB, LCK, and GSK-3β.

  • CAS Number: 869185-85-3
  • MF: C21H17ClFN3OS
  • MW: 413.896
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

A-769662

A-769662 is a potent, reversible AMPK activator with EC50 of 0.8 μM.

  • CAS Number: 844499-71-4
  • MF: C20H12N2O3S
  • MW: 360.386
  • Catalog: AMPK
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 630.1±55.0 °C at 760 mmHg
  • Melting Point: 268.39° C
  • Flash Point: 334.9±31.5 °C

AKTide-2T TFA

AKTide-2T is an excellent in vitro substrate for AKT and shows competitive inhibition of histone H2B phosphorylation with a Ki of 12 nM. AKTide-2T mimics the optimal phosphorylation sequence of Akt and is an inhibitory peptide with the wildtype AKTide lacking Thr in the S22 position[1].

  • CAS Number: 324029-01-8
  • MF: C74H114N28O20
  • MW: 1715.87000
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 153-156ºC
  • Flash Point: N/A

Copanlisib dihydrochloride

Copanlisib dihydrochloride (BAY 80-6946 dihydrochloride) is a potent, selective and ATP-competitive pan-class I PI3K inhibitor, with IC50s of 0.5 nM, 0.7 nM, 3.7 nM and 6.4 nM for PI3Kα, PI3Kδ, PI3Kβ and PI3Kγ, respectively. Copanlisib dihydrochloride has more than 2,000-fold selectivity against other lipid and protein kinases, except for mTOR. Copanlisib dihydrochloride has superior antitumor activity[1].

  • CAS Number: 1402152-13-9
  • MF: C23H30Cl2N8O4
  • MW: 553.442
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Kihadanin B

Kihadanin B is a citrus limonoid that can be purified from the peels of immature Citrus unshiu. Kihadanin B suppresses adipogenesis through repression of the Akt-FOXO1-PPARγ axis in 3T3-L1 adipocytes[1].

  • CAS Number: 73793-68-7
  • MF: C26H30O9
  • MW: 486.51100
  • Catalog: PPAR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-06885249

PF-249 is a potent, selective AMPK β1-containing complexes activator; increases the phosphorylation of the AMPK substrate ACC at S79 with EC50 of 296 nM, potently inhibits de novo lipogenesis (IC50=15 nM) in primary rat hepatocytes.

  • CAS Number: 1467059-70-6
  • MF: C17H16ClN3O3
  • MW: 345.783
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HL271

HL271, a chemical derivative of metformin (HY-B0627), is a potent AMPK activator that increases AMPK phosphorylation. HL271 attenuates aging-associated cognitive impairment[1][2].

  • CAS Number: 1422365-52-3
  • MF: C13H17ClF3N5O
  • MW: 351.76
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A