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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LY2090314

LY2090314 is a potent inhibitor of glycogen synthase kinase-3 (GSK-3) with IC50 values of 1.5 nM and 0.9 nM for GSK-3α and GSK-3β, respectively.

  • CAS Number: 603288-22-8
  • MF: C28H25FN6O3
  • MW: 512.535
  • Catalog: GSK-3
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MK-2206 free base

MK-2206 free base 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 free base. MK-2206 free base has anticancer activities[1][2].

  • CAS Number: 1032349-93-1
  • MF: C25H21N5O
  • MW: 407.46700
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(2α,3β)-2,3-Dihydroxylup-20(29)-en-28-oic acid

Alphitolic acid (Aophitolic acid) is an anti-inflammatory triterpene could found in quercus aliena. Alphitolic acid blocks Akt–NF-κB signaling to induce apoptosis. Alphitolic acid induces autophagy. Alphitolic acid has anti-inflammatory activity and down-regulates the NO and TNF-α production. Alphitolic acid can be used for cancer and inflammation research[1][2][3].

  • CAS Number: 19533-92-7
  • MF: C30H48O4
  • MW: 472.700
  • Catalog: Apoptosis
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 566.4±30.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 310.4±21.1 °C

VE-821

VE-821 is a potent ATP-competitive inhibitor of ATR with Ki/IC50 of 13 nM/26 nM.

  • CAS Number: 1232410-49-9
  • MF: C18H16N4O3S
  • MW: 368.410
  • Catalog: ATM/ATR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 568.4±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 297.6±30.1 °C

Hederacolchiside A1

Hederacolchiside A1, isolated from Pulsatilla chinensis, suppresses proliferation of tumor cells by inducing apoptosis through modulating PI3K/Akt/mTOR signaling pathway[1]. Hederacolchiside A1 has antischistosomal activity, affecting parasite viability both in vivo and in vitro[2].

  • CAS Number: 106577-39-3
  • MF: C47H76O16
  • MW: 897.097
  • Catalog: Apoptosis
  • Density: 1.36±0.1 g/cm3 (20 ºC 760 Torr)
  • Boiling Point: 967.2±65.0 °C at 760 mmHg
  • Melting Point: 253-255℃ (methanol , water )
  • Flash Point: 276.2±27.8 °C

ETP-45658

ETP-45658 is a potent PI3K inhibitor, with IC50s of 22.0 nM, 39.8 nM, 129.0 nM and 717.3 nM for PI3Kα, PI3Kδ, PI3Kβ and PI3Kγ, respectively. ETP-45658 also can inhibit DNA-PK (IC50=70.6 nM) and mTOR (IC50=152.0 nM). ETP-45658 can be used for the research of cancer[1][2].

  • CAS Number: 1198357-79-7
  • MF: C16H17N5O2
  • MW: 311.34
  • Catalog: DNA-PK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L-Leucine-2-13C,15N

L-Leucine-2-13C,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: 285977-88-0
  • MF: C513CH1315NO2
  • MW: 133.16
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Vevorisertib trihydrochloride

Vevorisertib (ARQ 751) (trihydrochloride) is an orally active, potent and selective pan-AKT serine/threonine kinase inhibitor against AKT1 (IC50=0.55 nM), AKT2 (IC50=0.81 nM), and AKT3 (IC50=1.31 nM). Vevorisertib (trihydrochloride), as a single agent or in combination with other anti-cancer agents, can be used for the research of solid tumors with PIK3CA / AKT / PTEN mutations[1][2][3][4].

  • CAS Number: 1416775-08-0
  • MF: C35H41Cl3N8O
  • MW: 696.11
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI3KC2α-IN-2

PI3KC2α-IN-2 is a potent and selective PI3KC2α inhibitor (IC50: 121 nM). PI3KC2α-IN-2 interacts with the ATP-binding site of PI3KC2α.. PI3KC2α-IN-2 can be used in the research of thrombosis, diabetes and cancers[1].

  • CAS Number: 2397679-77-3
  • MF: C25H20N6O3S2
  • MW: 516.59
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3-(pyridin-2-ylmethylidene)-1H-indol-2-one

(E/Z)-GSK-3β inhibitor 1 is a racemic compound of (E)-GSK-3β inhibitor 1 and (Z)-GSK-3β inhibitor 1 isomers. GSK-3β inhibitor 1 (compound 3a) is a glycogen synthase kinase 3β (GSK-3β) inhibitor and demonstrates high antidiabetic efficacy, with an IC50 of 4.9 nM[1].

  • CAS Number: 3367-88-2
  • MF: C14H10N2O
  • MW: 222.24200
  • Catalog: GSK-3
  • Density: 1.291g/cm3
  • Boiling Point: 457.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 230.3ºC

GSK3-IN-2

GSK3-IN-2 (compound 8) is a potent GSK3 inhibitor[1].

  • CAS Number: 380450-97-5
  • MF: C17H19N3OS
  • MW: 313.41726
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Garcinone C

Garcinone C, a xanthone derivative, is a natural compound extracted from Garcinia oblongifolia Champ that is used as an anti-inflammatory, analgesia, astringency and granulation-promoting medicine, and has potential cytotoxic effects on certain cancers. Garcinone C stimulates the expression levels of ATR and 4E-BP1, while efficiently inhibiting the expression levels of cyclin B1, cyclin D1, cyclin E2, cdc2, Stat3 and CDK7. Garcinone C significantly inhibits cell viability of the human Nasopharyngeal carcinoma (NPC) cell lines CNE1, CNE2, HK1 and HONE1 in a time‑ and dose‑dependent manner[1].

  • CAS Number: 76996-27-5
  • MF: C23H26O7
  • MW: 414.448
  • Catalog: ATM/ATR
  • Density: 1.367
  • Boiling Point: 689.0±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 239.7±25.0 °C

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

mTOR inhibitor-1

mTOR inhibitor-1 is a novel mTOR pathway inhibitor which can suppress cells proliferation and inducing autophagy.

  • CAS Number: 468747-17-3
  • MF: C16H15BrN2O3
  • MW: 363.21
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 262 °C
  • Flash Point: N/A

LRRK2-IN-8

LRRK2-IN-8 is a LRRK2 inhibitor. LRRK2-IN-8 inhibits LRRK2 (wt) and LRRK2 (G2019) with IC50s lower than 10 nM, and inhibits TYK2 and NUAK1 with IC50s of 10-100 nM[1].

  • CAS Number: 2770269-44-6
  • MF: C16H12F2N6
  • MW: 326.30
  • Catalog: LRRK2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI3Kδ-IN-16

PI3Kδ-IN-16 is a potent and selective inhibitor of PI3Kδ. PI3Kδ-IN-16 has a strong anti-proliferative effect on cells, causing cell cycle arrest and inducing apoptosis[1].

  • CAS Number: 2766437-35-6
  • MF: C22H26N6O2
  • MW: 406.48
  • 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

NVS-PI3-4

NVS-PI3-4 is a specific PI3Kγ inhibitor. NVS-PI3-4 can be used for the research of allergies, inflammatory and cancer diseases[1][2].

  • CAS Number: 941580-60-5
  • MF: C20H26N4O3S
  • MW: 402.51
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

bpV(phen) trihydrate

bpV(phen) trihydrate, a insulin-mimetic agent, is a potent protein tyrosine phosphatase (PTP) and PTEN inhibitor with IC50s of 38 nM, 343 nM and 920 nM for PTEN, PTP-β and PTP-1B, respectively. bpV(phen) trihydrate inhibits proliferation of the protozoan parasite Leishmania in vitro. bpV(phen) trihydrate strongly induces the secretion of a large number of chemokines and pro-inflammatory cytokines, and it activates a Th1-type pathway (IL-12, IFNγ). bpV(phen) trihydrate can also induce cell apoptosis, and has anti-angiogenic and anti-tumor activity[1][2][3][4][5].

  • CAS Number: 171202-16-7
  • MF: C12H14KN2O8V++
  • MW: 404.28800
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI4KIIIbeta-IN-11

PI4KIIIbeta-IN-11 is an inhibitor of PI4KIIIβ, with a mean pIC50 value of at least 9.1. PI4KIIIβ plays a key role in diseases research of RNA viruses and Plasmodium falciparum[1][2].

  • CAS Number: 2365241-79-6
  • MF: C33H39N7O3
  • MW: 581.71
  • Catalog: PI4K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MMP-9-IN-3

MMP-9-IN-3 is a MMP-9 inhibitor (IC50: 5.56 nM) that forms hydrogen bond with MMP-9. MMP-9-IN-3 also inhibits AKT activity (IC50: 2.11 nM). MMP-9-IN-3 shows cell cytotoxicity and induces cell apoptosis. MMP-9-IN-3 can be used in the research of cancers[1].

  • CAS Number: 2581824-48-6
  • MF: C29H25N3O4
  • MW: 479.53
  • Catalog: Apoptosis
  • 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

KU55933 (ATM Kinase Inhibitor)

KU-55933 is a potent ATM inhibitor with an IC50 and Ki of 12.9 and 2.2 nM, respectively, and is highly selective for ATM as compared to DNA-PK, PI3K/PI4K, ATR and mTOR.

  • CAS Number: 587871-26-9
  • MF: C21H17NO3S2
  • MW: 395.495
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 628.0±55.0 °C at 760 mmHg
  • Melting Point: 229.98° C
  • Flash Point: 333.6±31.5 °C

IM156

IM156 (HL156A), a chemical derivative of metformin (HY-B0627), is a potent AMPK activator that increases AMPK phosphorylation. IM156 attenuates aging-associated cognitive impairment in animal model[1][2].

  • CAS Number: 1422365-94-3
  • MF: C15H20F3N5O3
  • MW: 375.35
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Akt-l-1

AKT-I-1 is a selective inhibitor of Akt1, with an IC50 of 4.6 µM[1].

  • CAS Number: 473382-39-7
  • MF: C22H30N6
  • MW: 378.514
  • Catalog: Akt
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L-leucine

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

  • CAS Number: 61-90-5
  • MF: C6H13NO2
  • MW: 131.173
  • Catalog: mTOR
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 225.8±23.0 °C at 760 mmHg
  • Melting Point: 286-288 ºC
  • Flash Point: 90.3±22.6 °C

VP3.15

VP3.15 is a potent, orally bioavailable and CNS-penetrant dual phosphodiesterase (PDE)7- glycogen synthase kinase (GSK)3 inhibitor, with IC50s of 1.59 μM and 0.88 μM for PDE7 and GSK-3, respectively. VP3.15 has neuroprotective and neuroreparative activities, thus as potential combined anti-inflammatory and pro-remyelinating therapies for multiple sclerosis (MS)[1].

  • CAS Number: 1281681-54-6
  • MF: C20H22N4OS
  • MW: 366.48
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-739

A novel potent, pan-AMPK activator with similar potency for all AMPK heterotrimers; increases the phosphorylation of the AMPK substrate ACC at S79 with EC50 of 121 nM, potently inhibits de novo lipogenesis (IC50=25 nM) in primary rat hepatocytes; increases PGC1a transcription and mitochondrial content, effectively activats AMPK in hepatocytes and in skeletal muscle; caused a rapid lowering of plasma glucose levels with no impact on hepatic glucose production in diabetic mice.

  • CAS Number: 1852452-14-2
  • MF: C23H23ClN2O5
  • MW: 442.896
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LTURM 34

LTURM34 is a specific DNA-PK inhibitor with an IC50 of 0.034 μM.

  • CAS Number: 1879887-96-3
  • MF: C24H18N2O3S
  • MW: 414.476
  • Catalog: DNA-PK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 657.8±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 351.6±34.3 °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