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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reptoside

Reptoside, an iridoid glucoside, is a DNA damaging active agent. Reptoside has strong interactions with Trp352 and Tyr335 in AKT1[1].

  • CAS Number: 53839-03-5
  • MF: C17H26O10
  • MW: 390.38
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Linolenic acid

α-Linolenic acid, isolated from seed oils, is an essential fatty acid that cannot be synthesized by humans. α-Linolenic acid can affect the process of thrombotic through the modulation of PI3K/Akt signaling. α-Linolenic acid possess the anti-arrhythmic properties and is related to cardiovascular disease and cancer[1].

  • CAS Number: 463-40-1
  • MF: C18H30O2
  • MW: 278.430
  • Catalog: Akt
  • Density: 0.9±0.1 g/cm3
  • Boiling Point: 443.4±0.0 °C at 760 mmHg
  • Melting Point: -11 °C(lit.)
  • Flash Point: 275.7±14.4 °C

PKI-179

PKI-179 is a potent and orally active dual PI3K/mTOR inhibitor, with IC50s of 8 nM, 24 nM, 74 nM, 77 nM, and 0.42 nM for PI3K-α, PI3K-β, PI3K-γ, PI3K-δ and mTOR, respectively. PKI-179 also exhibits activity over E545K and H1047R, with IC50s of 14 nM and 11 nM, respectively. PKI-179 shows anti-tumor activity in vivo[1][2].

  • CAS Number: 1197160-28-3
  • MF: C25H28N8O3
  • MW: 488.54200
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PQR626

mTOR inhibitor-7 is an orally available, and brain-penetrant mTOR inhibitor extracted from patent WO2017198346A1, compound example 44, has an IC50 of 5 nM for mTOR. mTOR inhibitor-7 can be used for the research of neurological disorder[1].

  • CAS Number: 1927857-98-4
  • MF: C20H27F2N7O2
  • MW: 435.47
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Chromeceptin

Chromeceptin is an IGF signaling pathway inhibitor. Chromeceptin suppresses IGF2 at mRNA and protein levels in hepatocyte and HCC cells. Chromeceptin inhibits the Phosphorylation levels of AKT and mTOR[1].

  • CAS Number: 331859-86-0
  • MF: C19H16F3N3O
  • MW: 359.34500
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

YLF-466D

YLF-466D is a newly developed AMPK activator, which inhibits platelet aggregation.

  • CAS Number: 1273323-67-3
  • MF: C29H20ClNO3
  • MW: 465.92700
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI3Kβ and δ inhibitor 20a

PI3K-IN-6 (compound 20a) is an oral active and highly selective phosphoinositide 3-kinase (PI3K) β/δ inhibitor, with IC50 values of 7.8 nM/5.3 nM for PI3K β/δ, respectively. PI3K-IN-6 (compound 20a) has potential top treat phosphatase and tensin homolog (PTEN) feficient tumors[1].

  • CAS Number: 1842380-77-1
  • MF: C17H14Cl2FN9O
  • MW: 450.26
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TCS 21311

TCS 21311 (NIBR3049) is a potent, highly selective JAK3 inhibitor with an IC50 of 8 nM, it displays >100-fold selectivity over JAK1, JAK2 and TYK2. TCS 21311 (NIBR3049) inhibits PKCα, PKCθ, and GSK3β with IC50s of 13, 68, and 3 nM, respectively[1].

  • CAS Number: 1260181-14-3
  • MF: C27H25F3N4O4
  • MW: 526.50700
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Acetyl-Exenatide trifluoroacetate salt

Acetyl-Exenatideyes is an acetylated derivative of Exenatide. Exenatide has the function similar to insulin, which can be used for research of type 2 diabetes. Exenatide can promote Th17 differentiation, inhibits Tregs differentiation, downregulates PI3K/Akt/FoxO1 phosphorylation[1].

  • CAS Number: 305815-28-5
  • MF: C186H284N50O61S
  • MW: 4228.67
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-04802367

A potent, highly selective GSK-3 inhibitor with IC50 of 2.1 nM for human GSK-3β in enzyme assays; shows equal effectivity against GSK-3α and GSK-3β with IC50 of 10.0 and 9.0 nM respectively in mobility shift assays, inhibits phosphorylation of tau with an IC50 of 466 nM in a stable inducible CHO cell line over-expressing GSK-3β and substrate tau; modulates tau phosphorylation in vitro and in vivo.

  • CAS Number: 1962178-27-3
  • MF: C16H16ClN5O3
  • MW: 361.786
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ATR-IN-10

ATR-IN-10 is a potent and highly selective inhibitor of ataxia telangiectasia mutated and Rad3-Related (ATR) kinase with an IC50 value of 2.978 μM.

  • CAS Number: 2713577-93-4
  • MF: C27H24N4O
  • MW: 420.51
  • Catalog: ATM/ATR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CHIR-98014

CHIR-98014 is a potent, cell-permeable GSK-3 inhibitor with IC50s of 0.65 and 0.58 nM for GSK-3α and GSK-3β, respectively; it shows less potent activities against cdc2 and erk2.

  • CAS Number: 252935-94-7
  • 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

Isoprocurcumenol

Isoprocurcumenol is a guaiane type sesquiterpene, that can be isolated from Curcuma comosa. Isoprocurcumenol can activate EGFR signaling. Isoprocurcumenol increases the phosphorylation of ERK and Akt. Isoprocurcumenol promotes the proliferation of keratinocytes[1][2][3].

  • CAS Number: 102130-90-5
  • MF: C15H22O2
  • MW: 234.334
  • Catalog: EGFR
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 360.3±41.0 °C at 760 mmHg
  • Melting Point: 99.5-100.5 ºC (hexane )
  • Flash Point: 153.7±20.2 °C

Recilisib sodium

Recilisib sodium (ON 01210) is a radioprotectant, which can activate AKT, PI3K activities in cells[1].

  • CAS Number: 922139-31-9
  • MF: C16H12ClNaO4S
  • MW: 358.77
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CC214-2

CC214-2 is a potent and dual inhibitor of mTORC1/mTORC2. Mycobacterium tuberculosis modulates mammalian target of rapamycin (mTOR) signaling to impede autophagy. CC214-2 has the potential to shorten the duration of TB[1].

  • CAS Number: 1228012-18-7
  • MF: C20H25N5O3
  • MW: 383.44
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AChE/GSK-3β-IN-1

AChE/GSK-3β-IN-1 (compound GT15) is a potent, dual AChE/GSK-3β inhibitor with IC50 values of 1.2, 149.8 and 22.4 nM for hAChE , hBChE and hGSK-3β, respectively. AChE/GSK-3β-IN-1 penetrates the blood-brain barrier (BBB). AChE/GSK-3β-IN-1 has high kinase selectivity profiles for the CMGC kinase family. AChE/GSK-3β-IN-1 occupies the ATP binding site of DYRK1A. AChE/GSK-3β-IN-1 inhibits ROS expression and reduces oxidative stress. AChE/GSK-3β-IN-1 can be used for Alzheimer’s disease research[1].

  • CAS Number: 2412364-73-7
  • MF: C31H35N7O3S
  • MW: 585.72
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY-294,002 hydrochloride

LY294002 hydrochloride is a potent and broad-spectrum PI3K inhibitor, with IC50 values of 0.5, 0.57, and 0.97 μM for P110α, P110δ and P110β, respectively. LY294002 hydrochloride also inhibits CK2 with an IC50 of 98 nM. LY294002 hydrochloride can be used for pancreatic cancer research[1][2][3].

  • CAS Number: 934389-88-5
  • MF: C19H18ClNO3
  • MW: 343.80400
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Rapamycin (Sirolimus)

Rapamycin (Sirolimus) is a potent and specific mTOR inhibitor with an IC50 of 0.1 nM.

  • CAS Number: 53123-88-9
  • MF: C51H79NO13
  • MW: 914.172
  • Catalog: Autophagy
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 973.0±75.0 °C at 760 mmHg
  • Melting Point: 183-185°C
  • Flash Point: 542.3±37.1 °C

PI3Kδ-IN-7n

PI3Kδ-IN-5 (compound 7n) is a highly potent and selective inhibitor of PI3Kδ with an IC50 of 0.9 nM[1].

  • CAS Number: 2088525-31-7
  • MF: C23H20FN7O
  • MW: 429.45
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Db07107

DB07107 is a potent drug resistant T315I mutant Bcr-Abl tyrosine kinase inhibitor. DB07107 is also a potent Akt1 inhibitor with an IC50 value of 360 nM[1][2].

  • CAS Number: 552332-71-5
  • MF: C23H22N4O
  • MW: 370.45
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI3Kα-IN-7

PI3Kα-IN-7 (Compound A12) is a potent PI3Kα inhibitor. PI3Kα-IN-7 also inhibits PI3Kβ. PI3Kα-IN-7 decreases cancer cells mitochondrial membrane potential and induces apoptosis[1].

  • CAS Number: 2417098-53-2
  • MF: C17H22N8O2S
  • MW: 402.47
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

O-304

O-304 is a small molecule AMPK activator.

  • CAS Number: 1261289-04-6
  • MF: C16H11Cl2N3O2S
  • MW: 380.25
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Galegine hydrochloride

Galegine hydrochloride, a guanidine derivative, contributes to weight loss in mice. Guanidine hydrochloride is the compound derived from G. officinalis, which gave rise to the biguanides, metformin and phenformin. Galegine hydrochloride activates AMPK in 3T3-L1 adipocytes and L6 myotubes, as well as in the H4IIE rat hepatoma and HEK293 human kidney cell lines. Galegine hydrochloride has antibacterial activity, with minimum inhibitory concentration of 4 mg/L against Staphylococcus aureus strains[1][2].

  • CAS Number: 2368870-39-5
  • MF: C6H14ClN3
  • MW: 163.65
  • Catalog: Bacterial
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NV-5138

NV-5138, a leucine analog, is the first selective and orally active brain mTORC1 activator, binding to Sestrin2. NV-5138 possesses rapid antidepressant effects[1][2].

  • CAS Number: 2095886-80-7
  • MF: C7H13F2NO2
  • MW: 181.18
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-04691502

PF-04691502 is a potent and selective inhibitor of PI3K and mTOR. PF-04691502 binds to human PI3Kα, β, δ, γ and mTOR with Kis of 1.8, 2.1, 1.6, 1.9 and 16 nM, respectively.

  • CAS Number: 1013101-36-4
  • MF: C22H27N5O4
  • MW: 425.481
  • Catalog: mTOR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 682.5±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 366.5±34.3 °C

CDK8-IN-12

CDK8-IN-12 is an orally active, potent CDK8 inhibitor with a Ki of 14 nM. CDK8-IN-12 has off-target kinase inhibition on GSK-3α, GSK-3β, PCK-θ with Kis of 13 nM, 4 nM, 109 nM, respectively. CDK8-IN-12 shows potent anti-proliferative effects selectively on MV4-11 cell. CDK8-IN-12 is an anti-cancer agent[1].

  • CAS Number: 2613307-67-6
  • MF: C21H20ClN3O2
  • MW: 381.86
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Karanjin

Karanjin is a major active furanoflavonol constituent of Fordia cauliflora. Karanjin induces GLUT4 translocation in skeletal muscle cells by increasing AMPK activity. Karanjin can induce cancer cell death through cell cycle arrest and enhance apoptosis[1][2].

  • CAS Number: 521-88-0
  • MF: C18H12O4
  • MW: 292.285
  • Catalog: Apoptosis
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 463.0±45.0 °C at 760 mmHg
  • Melting Point: 156ºC
  • Flash Point: 233.8±28.7 °C

Artemisiane E

Artemisiane E (Compound 8) is a potent PI3K/AKT pathway inhibitor with an IC50 of 8.9 μM[1].

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

NTQ1062

NTQ1062 (compound 22b) is a potent and orally active Akt inhibitor with IC50s of 0.4 nM, 6.3 nM and 0.1 nM for Akt1, Akt2 and Akt3, respectively. NTQ1062 induces cell apoptosis and arrests the cell cycle at G0/G1 phase. NTQ1062 exhibits antiproliferation activity against various cancer cells. NTQ1062 exhibits potent antitumor efficacy in LNCap xenograft mouse model[1].

  • CAS Number: 2459489-66-6
  • MF: C25H31ClN6O2
  • MW: 483.01
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ro 90-7501

Ro 90-7501 is an amyloid β42 (Aβ42) fibril assembly inhibitor that reduces Aβ42-induced cytotoxicity (EC50 of 2 μM). Ro 90-7501 inhibits ATM phosphorylation and DNA repair. RO 90-7501 selectively enhances toll-like receptor 3 (TLR3) and RIG-I-like receptor (RLR) ligand-induced IFN-β gene expression and antiviral response[2]. Ro 90-7501 also inhibits protein phosphatase 5 (PP5) in a TPR-dependent manner[3]. Ro 90-7501 has significant radiosensitizing effects on cervical cancer cells[4].

  • CAS Number: 293762-45-5
  • MF: C20H16N6
  • MW: 340.38100
  • Catalog: Apoptosis
  • Density: 1.443g/cm3
  • Boiling Point: 751.035ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 449.122ºC