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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ATM Inhibitor-1

ATM Inhibitor-1 is a highly potent, selective and orally active ATM inhibitor, with an IC50 of 0.7 nM, shows weak activity against mTOR (IC50, 21 μM), DNAPK (IC50, 2.8 μM), PI3Kα (IC50, 3.8 μM), PI3Kβ (IC50, 10.3 μM), PI3Kγ (IC50, 3 μM) and PI3Kδ (IC50, 0.73 μM). ATM Inhibitor-1 exhibits anti-tumor activity[1].

  • CAS Number: 2135639-94-8
  • MF: C27H36N6O3
  • MW: 492.61
  • Catalog: ATM/ATR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK-3 inhibitor 3

GSK-3 inhibitor 3 is a selective, orally active and brain-penetrant inhibitor of GSK-3, with IC50s of 0.35 nM and 0.25 nM for GSK-3α and GSK-3β, respectively. GSK-3 inhibitor 3 lowers levels of tau protein phosphorylation at S396 in a triple-transgenic mouse Alzheimer’s disease model, with IC50 of 10 nM. GSK-3 inhibitor 3 can be used for neurological disease research[1].

  • CAS Number: 2227279-84-5
  • MF: C23H15FN6O
  • MW: 410.40
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pyridine, 4-[5-[[(3-phenyl-1,2,4-oxadiazol-5-yl)methyl]thio]-1,3,4-oxadiazol-2-yl]

GS87 is a highly specific and potent GSK3 inhibitor with IC50s of 415nM and 521nM for GSK3α and GSK3β, respectively. GS87 induces differentiation of acute myeloid leukemia (AML) cell lines by effectively activating GSK3-dependent signaling components including MAPK signaling. GS87 modulates key GSK3 target proteins involved in cell proliferation and differentiation more effectively than Lithium and SB415285 (SB). GS87 has the potential for acting as a differentiation agent for non-promyelocytic AML research[1].

  • CAS Number: 919936-70-2
  • MF: C16H11N5O2S
  • MW: 337.35600
  • Catalog: GSK-3
  • Density: 1.47±0.1 g/cm3 (20 °C, 760 mmHg)
  • Boiling Point: 572.5±60.0 °C (760 mmHg)
  • Melting Point: N/A
  • Flash Point: N/A

6-O-Isobutyrylbritannilactone

6-O-Isobutyrylbritannilactone is a natural melanogenesis inhibitor. 6-O-Isobutyrylbritannilactone, a sesquiterpene, can be isolated from the flowers of Inula britannica. 6-O-Isobutyrylbritannilactone inhibits IBMX (HY-12318)-induced melanin production in B16F10 cells. 6-O-Isobutyrylbritannilactone also regulates ERK, PI3K/AKT, and CREB, shows antimelanogenic activity in zebrafish embryos models[1].

  • CAS Number: 1259933-02-2
  • MF: C19H28O5
  • MW: 336.42
  • Catalog: Epigenetic Reader Domain
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AKT-IN-12

AKT-IN-12 (compound 3e) is a potent Akt kinase inhibitor with an IC50 value of 0.55 μM. AKT-IN-12 induces G0/G1 cell cycle arrest and apoptosis. AKT-IN-12 also inhibits p-AKT, p-ERK, and activates p-JNK, JNK. AKT-IN-12 can be used for researching leukemia[1].

  • CAS Number: 2396718-52-6
  • MF: C42H46N2O7S
  • MW: 722.89
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Alpelisib (BYL719)

Alpelisib (BYL-719) is a potent and selective PI3Kα inhibitor with an IC50 of 5 nM.

  • CAS Number: 1217486-61-7
  • MF: C19H22F3N5O2S
  • MW: 441.470
  • Catalog: PI3K
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

niloticin

Niloticin, tetracyclic triterpenoid compound, is a osteoclastogenesis inhibitor. Niloticin shows anti-viral, antioxidative, and mosquitocidal activities. Niloticin inhibits osteoclastogenesis by blocking RANKL-RANK interaction and suppressing the AKT, MAPK, and NF-κB signaling pathways[1].

  • CAS Number: 115404-57-4
  • MF: C30H48O3
  • MW: 456.70
  • Catalog: Akt
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 538.5±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 165.4±22.2 °C

TDZD-8

TDZD-8 is an inhibitor of GSK-3β, with an IC50 of 2 μM; TDZD-8 shows less potent activities against Cdk-1/cyclin B, CK-II, PKA, and PKC, with all IC50s of >100 μM.

  • CAS Number: 327036-89-5
  • MF: C10H10N2O2S
  • MW: 222.264
  • Catalog: GSK-3
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 335.5±35.0 °C at 760 mmHg
  • Melting Point: 63-64.4ºC
  • Flash Point: 156.7±25.9 °C

L-Leucine-18O2

L-Leucine-18O2 is the 18O-labeled L-Leucine. L-Leucine is an essential branched-chain amino acid (BCAA), which activates the mTOR signaling pathway[1].

  • CAS Number: 73579-45-0
  • MF: C6H13N18O2
  • MW:
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ATR-IN-18

ATR-IN-18 (compound 2) is an orally active and potent ATR kinase inhibitor, with an IC50 of 0.69 nM. ATR-IN-18 shows antiproliferative activity in LoVo cells, with an IC50 of 37.34 nM. ATR-IN-18 has anti-tumor activity[1].

  • CAS Number: 2766407-55-8
  • MF: C19H22F3N7O5S
  • MW: 517.48
  • Catalog: ATM/ATR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Musk ketone

Musk ketone (MK) is a widely used artificial fragrance. Musk ketone shows mutagenic and comutagenic effects in Hep G2 cells and induces neural stem cell proliferation and differentiation in cerebral ischemia via activation of the PI3K/Akt signaling pathway. In the brain, musk ketone is neuroprotective against stroke injury through inhibition of cell apoptosis[1][2][3].

  • CAS Number: 81-14-1
  • MF: C14H18N2O5
  • MW: 294.30
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 369.0±42.0 °C at 760 mmHg
  • Melting Point: 135-139 °C(lit.)
  • Flash Point: 153.2±20.7 °C

AZ31

AZ31 is a a potent, highly selective, and orally active ATM inhibitor with an IC50 of <1.2 nM for ATM enzyme, and an IC50 of 46 nM for ATM in cell. AZ31 shows excellent selectivity over ATR (>500-fold) and excellent PIKK-family selectivity and pan-kinase selectivity. AZ31 is a potent radiosensitizer in vitro, it can be used for the research of cancer[1].

  • CAS Number: 2088113-98-6
  • MF: C24H28N4O3
  • MW: 420.50412
  • Catalog: ATM/ATR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK-3β inhibitor 12

GSK-3β inhibitor 12 (compound 15) is an inhibitor of GSK-3β. GSK-3β inhibitor 12 inhibits 49.11% and 37.11% activity of 25 μM and 50 μM GSK-3β, respectively. GSK-3β inhibitor 12 can be used for the research of neurodegenerative diseases[1].

  • CAS Number: 784170-07-6
  • MF: C14H13N3OS
  • MW: 271.34
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI3Kδ/γ-IN-2

PI3Kδ/γ-IN-2 is a potent PI3Kδ and PI3Kγ dual inhibitor with IC50s of 1 nM and 4.3 nM, respectively. PI3Kδ/γ-IN-2 has favorable oral bioavailability. PI3Kδ/γ-IN-2 has potential for battling B-cell malignancies[1].

  • CAS Number: 2412195-89-0
  • MF: C25H21ClN8O
  • MW: 484.94
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AMPK activator 8

AMPK activator 8 (Compound 2) is an AMP-activated protein kinase (AMPK) activator with EC50s of 11, 27, 4, 2, and 4 nM for rAMPK α1β1γ1, rAMPK α2β1γ1, rAMPK α1β2γ1, rAMPK α2β2γ1, rAMPK α2β2γ3, respectively. AMPK activator 8 can be used for the research of type 2 diabetes[1].

  • CAS Number: 1852451-96-7
  • MF: C25H21ClN2O6
  • MW: 480.90
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PIK-90

PIK-90 is a DNA-PK and PI3K inhibitor, which inhibits p110α, p110γ and DNA-PK with IC50s of 11, 18 and 13 nM, respectively.

  • CAS Number: 677338-12-4
  • MF: C18H17N5O3
  • MW: 351.36
  • Catalog: DNA-PK
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 817.3±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 448.1±34.3 °C

Phospho-Glycogen Synthase Peptide-2(substrate) TFA

Phospho-Glycogen Synthase Peptide-2 (substrate) is peptide substrate for glycogen synthase kinase-3 (GSK-3) and can be used for affinity purification of protein-serine kinases[1].

  • CAS Number: 851366-97-7
  • MF: C122H193N40O48P
  • MW: 3019.05
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PIK-293

PIK-293, an analog of IC87114, is a PI3K inhibitor, with IC50 values of 0.24 μM, 10 μM, 25 μM and 100 μM for p110δ, p110β, p110γ and p110α, respectively[1].

  • CAS Number: 900185-01-5
  • MF: C22H19N7O
  • MW: 397.433
  • Catalog: PI3K
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 657.3±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 351.3±34.3 °C

IMM-H007

IMM-H007 is a potent TGFβ1 (transforming growth factor β1) antagonist. IMM-H007 has protective effects in cardiovascular diseases via activation of AMPK (AMP-activated protein kinase). IMM-H007 negatively regulates endothelium inflammation through inactivating NF-κB and JNK/AP1 signaling. IMM-H007 inhibits ABCA1 degradation. IMM-H007 resolves hepatic steatosis in HFD-fed hamsters by the regulation of lipid metabolism. IMM-H007 can be used for the research of nonalcoholic fatty liver disease (NAFLD) and inflammatory atherosclerosis[1][2][3].

  • CAS Number: 1221412-23-2
  • MF: C22H23N5O8
  • MW: 485.45
  • Catalog: AMPK
  • Density: 1.54±0.1 g/cm3
  • Boiling Point: 684.6±65.0 °C
  • Melting Point: N/A
  • Flash Point: N/A

PI3K-IN-33

PI3K-IN-33 (Compound 6e) 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-33 arrests cell cycle at G2/M phase and induces apoptosis. PI3K-IN-33 can be used in leukemia research[1].

  • CAS Number: 2458163-92-1
  • MF: C23H21BrN6O2
  • MW: 493.36
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Actein

Actein is a triterpene glycoside isolated from the rhizomes of Cimicifuga foetida. Actein suppresses cell proliferation, induces autophagy and apoptosis through promoting ROS/JNK activation, and blunting AKT pathway in human bladder cancer. Actein has little toxicity in vivo[1][2].

  • CAS Number: 18642-44-9
  • MF: C37H56O11
  • MW: 676.834
  • Catalog: Apoptosis
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 246-250ºC
  • Flash Point: N/A

L-Leucine-d3

L-Leucine-d3 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: 87828-86-2
  • MF: C6H10D3NO2
  • MW: 134.191
  • Catalog: mTOR
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 225.8±23.0 °C at 760 mmHg
  • Melting Point: >300ºC(lit.)
  • Flash Point: 90.3±22.6 °C

1H-Indazole

Indazole, also called isoindazole, a heterocyclic aromatic organic compound. Its derivatives display a broad variety of biological activities including anti-inflammatory, antibacterial, anti-HIV, antiarrhythmic, antifungal and antitumour properties. Indazole and its derivatives can be used for research of cancer, neurological disorders, cardiovascular diseases, gastrointestinal diseases[1][2][3][4][5].

  • CAS Number: 271-44-3
  • MF: C7H6N2
  • MW: 118.136
  • Catalog: LRRK2
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 270.0±9.0 °C at 760 mmHg
  • Melting Point: 145-148 °C(lit.)
  • Flash Point: 128.5±11.7 °C

CC-115 hydrochloride

CC-115 hydrochloride is a potent and dual DNA-PK and mTOR kinase inhibitor with IC50s of 13 nM and 21 nM, respectively. CC-115 blocks both mTORC1 and mTORC2 signaling.

  • CAS Number: 1300118-55-1
  • MF: C16H17ClN8O
  • MW: 372.812
  • Catalog: DNA-PK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Coronarin A

Coronarin A is an orally active natural compound that inhibits mTORC1 and S6K1 to increase IRS1 activity. Coronarin A shows anti-inflammatory activity and can also be used for type 2 diabetes mellitus research[1].

  • CAS Number: 119188-33-9
  • MF: C20H28O2
  • MW: 300.435
  • Catalog: Ribosomal S6 Kinase (RSK)
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 401.1±40.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 196.4±27.3 °C

l-leucine-2-d1

L-Leucine-d1 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: 89836-93-1
  • MF: C6H12DNO2
  • MW: 132.17900
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: >300 °C(lit.)
  • Flash Point: N/A

AZD8154

AZD8154 is a novel inhaled selective PI3Kγδ dual inhibitor targeting airway inflammatory disease.

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

WNY1613

WNY1613 is a potent and selective PI3Kδ inhibitor with piperazinone-containing purine scaffold. WNY1613 induces cancer cell apoptosis and inhibits the phosphorylation of PI3K downstream components in NHL cell lines. WNY1613 exhibits anti-NHL activity in vitro and in vivo[1].

  • CAS Number: 2650546-39-5
  • MF: C29H35N9O3
  • MW: 557.65
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KU-0060648

KU-0060648 is a dual inhibitor of PI3K and DNA-PK with IC50s of 4 nM, 0.5 nM, 0.1 nM, 0.594 nM and 8.6 nM for PI3Kα, PI3Kβ, PI3Kγ, PI3Kδ and DNA-PK, respectively[1].

  • CAS Number: 881375-00-4
  • MF: C33H34N4O4S
  • MW: 582.713
  • Catalog: DNA-PK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 819.9±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 449.7±34.3 °C

PI3Kγ inhibitor 5

PI3Kγ inhibitor 5 is an inhibitor of phosphoinositide 3-kinase γ (PI3Kγ) with an IC50 value of 34 nM.

  • CAS Number: 2566569-31-9
  • MF: C28H32F2N6O4
  • MW: 554.59
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A