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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IM-12

IM-12 is an inhibitor of GSK-3β, with an IC50 of 53 nM, and also enhances Wnt signalling.

  • CAS Number: 1129669-05-1
  • MF: C22H20FN3O2
  • MW: 377.411
  • Catalog: GSK-3
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 600.2±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 316.8±31.5 °C

GSK621

GSK621 is a specific AMPK activator, with IC50 values of 13-30 μM for AML cells. GSK621 induces autophagy and apoptosis. GSK621 induces eiF2α phosphorylation-a hallmark of UPR activation[1].

  • CAS Number: 1346607-05-3
  • MF: C26H20ClN3O5
  • MW: 489.907
  • Catalog: Apoptosis
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PS48

PS48 is an activator of PDK1 with an AC50 of 8 μM.

  • CAS Number: 1180676-32-7
  • MF: C17H15ClO2
  • MW: 286.753
  • Catalog: PDK-1
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 444.1±24.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 222.4±22.9 °C

PI3K/mTOR Inhibitor-13 sodium

PI3K/mTOR Inhibitor-13 sodium is an orally active dual inhibitor of phosphoinositol 3-kinase (PI3K) and mTOR kinase. PI3K/mTOR Inhibitor-13 sodium has potential applications in sexual diseases, solid tumor and idiopathic pulmonary fibrosis (IPF)[1][2].

  • CAS Number: 2361009-23-4
  • MF: C20H13F2N5NaO3S
  • MW: 464.40
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sennidin B

Sennidin B, a stereoisomer isolated from the leaves of Cassia angustifolia, has lower activity than Sennidin A. Sennidin A inhibits HCV NS3 helicase, with an IC50 of 0.8 μM. Sennidin A induces phosphorylation of Akt and glucose transporter 4 (GLUT4) translocation. Sennidin A stimulates the glucose incorporation [1][2].

  • CAS Number: 517-44-2
  • MF: C30H18O10
  • MW: 538.458
  • Catalog: HCV
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 801.8±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 452.6±30.8 °C

Demethylasterriquinone B1

Demethylasterriquinone B1 is a selective insulin receptor activator. Demethylasterriquinone B1 stimulates tyrosine phosphorylation of the IR β subunit, and the activation of PIK3 and AKT[1].

  • CAS Number: 78860-34-1
  • MF: C32H30N2O4
  • MW: 506.59200
  • Catalog: Akt
  • Density: 1.335g/cm3
  • Boiling Point: 780.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 425.6ºC

PRE-084 hydrochloride

PRE-084 is a highly selective σ1 receptor (S1R) agonist, with an IC50 of 44 nM. PRE-084 exhibits good neuroprotective effects, can improve motor function and motor neuron survival in mice. PRE-084 also can ameliorate myocardial ischemia-reperfusion injury in rats by activating the Akt-eNOS pathway[1][2][3][4].

  • CAS Number: 138847-85-5
  • MF: C19H27NO3
  • MW: 317.42
  • Catalog: Sigma Receptor
  • Density: 1.103g/cm3
  • Boiling Point: 446.6ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 223.9ºC

PI3K/mTOR Inhibitor-7

PI3K/mTOR Inhibitor-7 (Compound 19i) is a potent and dual inhibitor of PI3K/mTOR. PI3K/mTOR Inhibitor-7 shows 4.7-fold higher potency than the positive control gedatolisib (0.3 vs. 1.4 μM, IC50 values). PI3K/mTOR Inhibitor-7 significantly suppresses the PI3K/Akt/mTOR signaling pathway at 10 μM. PI3K/mTOR Inhibitor-7 has the potential for the research of cancer diseases[1].

  • CAS Number: 2456295-65-9
  • MF: C29H33N9O4
  • MW: 571.63
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Akt1&PKA-IN-1

Akt1&PKA-IN-1 is a potent dual Akt/PKA inhibitor with IC50 values of 0.03 , 0.11 μM, and 9.8 μM for PKAa, Akt, and CDK2, respectively. Akt1&PKA-IN-1 is selective for cyclin-dependent kinase 2 (CDK2)[1].

  • CAS Number: 1334107-58-2
  • MF: C20H17Cl2N3O
  • MW: 386.27
  • Catalog: CDK
  • Density: N/A
  • 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

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

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

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

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

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

Ack1 inhibitor 1

Ack1 inhibitor 1 is a potent, selective, and orally active inhibitor of ACK1 kinase with an IC50 value of 2.1 nM. Ack1 inhibitor 1 inhibits the phosphorylation of ACK1 and activation of downstream AKT. Ack1 inhibitor 1 has anti-tumor activity[1].

  • CAS Number: 2924415-92-7
  • MF: C39H40F3N7O4
  • MW: 727.77
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

[7,7'-Bi-4aH-xanthene]-4a,4'a-dicarboxylicacid,2,2',3,3',4,4',9,9'-octahydro-1,1',4,4',8,8'-hexahydroxy-3,3'-dimethyl-9,9'-dioxo-,4a,4'a-dimethyl ester, (3S,3'S,4R,4'R,4aR,4'aR)-

Secalonic acid D is a toxic compound against tumor cells. Secalonic acid D can be isolated from the metabolites of Aspergillus aculeatus. Secalonic acid D activates GSK3-β, and degrades β-catenin. Thus, Secalonic acid D down-regulates c-Myc expression, arrests cell cycle at G1 phase, induces cell apoptosis[1][2].

  • CAS Number: 35287-69-5
  • MF: C32H30O14
  • MW: 638.57200
  • Catalog: Apoptosis
  • Density: 1.67g/cm3
  • Boiling Point: 846ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 273.7ºC

Amarogentin

Amarogentin is a secoiridoid glycoside that is mainly extracted from Swertia and Gentiana roots. Amarogentin exhibits many biological effects, including anti-oxidative, anti-tumour, and anti-diabetic activities. Amarogentin exerts hepatoprotective and immunomodulatory effects. Amarogentin promotes apoptosis, arrests G2/M cell cycle and downregulates of PI3K/Akt/mTOR signalling pathways. Amarogentin exerts beneficial vasculo-metabolic effect by activating AMPK[1][2][3].

  • CAS Number: 21018-84-8
  • MF: C29H30O13
  • MW: 586.541
  • Catalog: Apoptosis
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 928.5±65.0 °C at 760 mmHg
  • Melting Point: 229-230ºC
  • Flash Point: 306.9±27.8 °C

GSK2269557

Nemiralisib hydrochloride (GSK2269557) is a potent and highly selective PI3Kδ inhibitor with a pKi of 9.9.

  • CAS Number: 1254036-77-5
  • MF: C26H29ClN6O
  • MW: 477.00
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Compound L

STL127705 (Compound L) is a Ku 70/80 heterodimer protein inhibitor, inhibits Ku70/80-DNA interaction, with an IC50 of 3.5 μM. STL127705 also inhibits Ku-dependent activation of DNA-PKCS kinase (IC50, 2.5 μM)[1].

  • CAS Number: 1326852-06-5
  • MF: C22H20FN5O4
  • MW: 437.42
  • Catalog: DNA-PK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Anticancer agent 164

CML-IN-1 (compound 7) is a potent anticancer agent. CML-IN-1 displays very good induced-apoptosis effect for human chronic myeloid leukemia (CML) cell line K562. CML-IN-1 exerts its effect via a significantly reduced protein phosphorylation of PI3K/Akt signal pathway. CML-IN-1 (compound 4) also inhibits cell proliferation by suppressing the MEK/ERK signaling pathway in colorectal cancer[1][2].

  • CAS Number: 2235393-30-1
  • MF: C21H23F3N8O2S2
  • MW: 540.58
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SAR-260301

SAR-260301 is a selective PI3Kβ inhibitor with an IC50 of 23 nM.

  • CAS Number: 1260612-13-2
  • MF: C19H22N4O3
  • MW: 354.403
  • Catalog: PI3K
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

bpV(HOpic)

BpV(HOpic) is a potent and selective inhibitor of PTEN with an IC50 of 14 nM. Nanocarrier-BpV(HOpic) has neuroprotective activity[1][2].

  • CAS Number: 722494-26-0
  • MF: C6H4K2NO8V
  • MW: 347.23600
  • Catalog: PTEN
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Idelalisib (CAL-101)

Idelalisib (CAL-101) is a highly selective and potent p110δ inhibitor with an IC50 of 2.5 nM, showing 40- to 300-fold selectivity for p110δ over other PI3K class I enzymes.

  • CAS Number: 870281-82-6
  • MF: C22H18FN7O
  • MW: 415.423
  • Catalog: Autophagy
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

8-Chloroadenosine

8-Chloroadenosine (8-Cl-Ado), a unique ribonucleoside analog, depletes endogenous ATP that subsequently induces the phosphorylation and activation of AMPK. 8-Chloroadenosine induces autophagic cell death. 8-Chloroadenosine effectively inhibited in vivo tumor growth in mice[1].

  • CAS Number: 34408-14-5
  • MF: C10H12ClN5O4
  • MW: 301.69
  • Catalog: Autophagy
  • Density: 2.2±0.1 g/cm3
  • Boiling Point: 707.4±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 381.6±35.7 °C

Rutin hydrate

Rutin hydrate is a flavonol glycoside, able to cross the blood-brain barrier, and acts by inhibiting JNK and ERK1/2 activation and activating mTOR signalling.

  • CAS Number: 207671-50-9
  • MF: C27H3O16.xH2O
  • MW: 664.56300
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 195°C dec. (Lit.)
  • Flash Point: N/A

1-Deoxynojirimycin hydrochloride

1-Deoxynojirimycin hydrochloride (Duvoglustat hydrochloride) is a potent and orally active α-glucosidase inhibitor. 1-Deoxynojirimycin hydrochloride suppresses postprandial blood glucose and is widely used for diabetes mellitus. 1-Deoxynojirimycin hydrochloride possesses antihyperglycemic, anti-obesity, and antiviral features[1][2].

  • CAS Number: 73285-50-4
  • MF: C6H14ClNO4
  • MW: 199.633
  • Catalog: PI3K
  • Density: 1.456 g/cm3
  • Boiling Point: 361.1ºC at 760 mmHg
  • Melting Point: 195-196ºC
  • Flash Point: 197.3ºC

CMX-2043

CMX-2043 is a novel analogue of α-Lipoic Acid (HY-N0492). CMX-2043 is effective in antioxidant effect, activation of insulin receptor kinase, soluble tyrosine kinase, and Akt phosphorylation. CMX-2043 shows protection against ischemia-reperfusion injury (IRI) in rat model[1][2].

  • CAS Number: 910627-26-8
  • MF: C16H26N2O6S2
  • MW: 406.52
  • Catalog: Tyrosinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PIK-93

PIK-93 is the first potent, synthetic PI4K (PI4KIIIβ) inhibitor with IC50 of 19 nM, and also inhibits PI3Kγ and PI3Kα with IC50 of 16 nM and 39 nM, respectively.

  • CAS Number: 593960-11-3
  • MF: C14H16ClN3O4S2
  • MW: 389.87800
  • Catalog: PI4K
  • Density: 1.48 g/cm3
  • Boiling Point: 611.8ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 323.8ºC

ZDWX-25

ZDWX-25 is a highly potent GSK-3β and DYRK1A dual inhibitor with an IC50 value of 71 nM for GSK-3β. ZDWX-25 possesses significant cytotoxic activities against SH-SY5Y and HL-7702 cells. ZDWX-25 can be used for researching alzheimer's disease[1].

  • CAS Number: 2668297-70-7
  • MF: C17H15N3O3
  • MW: 309.32
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A