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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CYH33

CYH33 (CYH-33) is a novel potent, PI3Kα-selective inhibitor with IC50 of 5.9 nM/598 nM/ 78.7 nM/225 nM aginst class I PI3K isoform α/β/δ/γ, respectively; also displays little to no activity against more than 300 kinases; inhibits PI3K/AKT/mTOR signaling in glioblastoma U87MG and rhabdomyosarcoma Rh30 cells, shows potent anti-proliferative activity in against cell proliferation in a panel cancer cell lines originated from breast, lung, ovary and colon, prostate etc.; shows significant efficacy to inhibit the growth of SKOV-3 xenograft. Solid Tumors Phase 1 Clinical

  • CAS Number: 1494684-28-4
  • MF: C24H29F3N8O5S
  • MW: 598.602
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AKT inhibitor VIII

AKT inhibitor VIII is a cell-permeable quinoxaline compound that has been shown to potently, selectively, allosterically, and reversibly inhibit Akt1, Akt2, and Akt3 activity with IC50s of 58 nM, 210 nM, and 2119 nM, respectively.

  • CAS Number: 612847-09-3
  • MF: C34H29N7O
  • MW: 551.640
  • Catalog: Akt
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 242-245ºC (dec.)
  • Flash Point: N/A

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

BBD130

NVP-BBD130 is a potent, stable, ATP-competitive and orally active dual PI3K and mTOR inhibitor[1].

  • CAS Number: 853910-61-9
  • MF: C28H21N5O
  • MW: 443.499
  • Catalog: mTOR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 693.7±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 373.3±34.3 °C

Quercetin

Quercetin is a natural flavonoid which activates or inhibits the activities of a number of proteins. Quercetin can activate SIRT1 and inhibit PI3K with IC50s of 2.4 μM, 3.0 μM, 5.4 μM for PI3K γ, PI3K δ and PI3K β, respecti

  • CAS Number: 117-39-5
  • MF: C15H10O7
  • MW: 302.236
  • Catalog: Apoptosis
  • Density: 1.8±0.1 g/cm3
  • Boiling Point: 642.4±55.0 °C at 760 mmHg
  • Melting Point: 314-317°C
  • Flash Point: 248.1±25.0 °C

1-Azakenpaullone

1-Azakenpaullone (1-Akp) is a highly selective and ATP-competitive inhibitor of glycogen synthase kinase-3 β (GSK-3β), with an IC50 value of 18 nM[1].

  • CAS Number: 676596-65-9
  • MF: C15H10BrN3O
  • MW: 328.163
  • Catalog: GSK-3
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 648.8±50.0 °C at 760 mmHg
  • Melting Point: >290ºC (dec.)
  • Flash Point: 346.2±30.1 °C

Triciribine

Triciribine is a DNA synthesis inhibitor, also inhibits Akt and HIV-1/2 with IC50 of 130 nM, and 0.02-0.46 μM, respectively.

  • CAS Number: 35943-35-2
  • MF: C13H16N6O4
  • MW: 320.304
  • Catalog: HIV
  • Density: 2.0±0.1 g/cm3
  • Boiling Point: 718.5±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 388.3±35.7 °C

Malvidin-3-O-arabinoside chloride

Malvidin-3-O-arabinoside chloride ameliorates ethyl carbamate-induced oxidative damage by stimulating AMPK-mediated autophagy[1].

  • CAS Number: 28500-04-1
  • MF: C22H23O11.Cl
  • MW: 498.864
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

mTOR inhibitor WYE-28

mTOR inhibitor WYE-28 (compound 28) is a selective inhibitor of mTOR>/b< (IC50)=0.08 nM. mTOR inhibitor WYE-28 inhibits PI3Kα with an IC50 value of 6 nM. mTOR inhibitor WYE-28 shows a metabolic time (T1/2) in nude mouse microsomes of 13 min[1].

  • CAS Number: 1062172-60-4
  • MF: C30H34N8O5
  • MW: 586.64
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

cis,trans-Germacrone

cis,trans-Germacrone is a isomer of Germacrone (HY-N0440). Germacrone exhibits a wide range of antitumor, antioxidant and anti-inflammatory effects. Germacrone inhibits lung cancer cell proliferation and alters the Akt/MDM2/p53. Germacrone also arrests cell cycle at G1/S phase[1].

  • CAS Number: 32663-51-7
  • MF: C15H22O
  • MW: 218.33500
  • Catalog: MDM-2/p53
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CHMFL-PI4K-127

CHMFL-PI4K-127 (compound 15g) is an orally active, potent and high selective PfPI4K (Plasmodium falciparum PI4K kinase) inhibitor, with an IC50 of 0.9 nM. CHMFL-PI4K-127 exhibits potent activity against 3D7 Plasmodium falciparum, with an EC50 of 25.1 nM. CHMFL-PI4K-127 shows antimalaria efficacy[1].

  • CAS Number: 2377604-81-2
  • MF: C18H15ClN4O3S
  • MW: 402.85
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ROCK-IN-5

ROCK-IN-5 (compound I-B-37) is a potent inhibitor of ROCK, ERK, GSK, and AGC protein kinases. ROCK-IN-5 has the potential for proliferative, cardiac and neurodegenerative diseases research[1].

  • CAS Number: 692870-25-0
  • MF: C16H11ClFN3OS
  • MW: 347.79
  • Catalog: ROCK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SB216763

SB 216763 is potent, selective and ATP-competitive GSK-3 inhibitor with IC50s of 34.3 nM for both GSK-3α and GSK-3β.

  • CAS Number: 280744-09-4
  • MF: C19H12Cl2N2O2
  • MW: 371.217
  • Catalog: Autophagy
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 598.1±50.0 °C at 760 mmHg
  • Melting Point: 287-288.6ºC(lit.)
  • Flash Point: 315.5±30.1 °C

[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

4'-Hydroxywogonin

4′-Hydroxywogonin (8-Methoxyapigenin), a flavonoid, could be isolated from a variety of plants including Scutellaria barbata and Verbena littoralis. 4′-Hydroxywogonin has anti-inflammatory activity via TAK1/IKK/NF-κB, MAPKs and PI3/AKT signaling pathways. 4′-Hydroxywogonin inhibits angiogenesis by disrupting PI3K/AKT signaling. 4′-Hydroxywogonin inhibits cell proliferation and induces apoptosis[1][2][3].

  • CAS Number: 57096-02-3
  • MF: C16H12O6
  • MW: 300.263
  • Catalog: Apoptosis
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 578.1±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 220.9±23.6 °C

TG100713

TG 100713 is an inhibitor of PI3K, with IC50s of 24, 50, 165, and 215 nM for PI3Kδ, γ, α and β isoforms respectively[1].

  • CAS Number: 925705-73-3
  • MF: C12H10N6O
  • MW: 254.247
  • Catalog: PI3K
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 646.4±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 344.8±34.3 °C

RP106

Aloisine RP106 (compound 38) is a potent inhibitor of Cdk1/cyclin B, Cdk5/p25, and GSK3 with IC50s of 0.70µM, 1.5µM, 0.92 µM, respectively[1].

  • CAS Number: 496864-15-4
  • MF: C16H17N3O
  • MW: 267.32600
  • Catalog: CDK
  • Density: 1.155g/cm3
  • Boiling Point: N/A
  • Melting Point: 182-184ºC
  • Flash Point: N/A

PQR-309

Bimiralisib is a potent, brain-penetrant, orally bioavailable, pan-class I PI3K/mTOR inhibitor with IC50s of 33 nM, 451 nM, 661 nM, 708 nM and 89 nM for PI3Kα, PI3Kδ, PI3Kβ, PI3Kγ and mTOR, respectively. Bimiralisib is an mTORC1 and mTORC2 inhibitor.

  • CAS Number: 1225037-39-7
  • MF: C17H20F3N7O2
  • MW: 411.382
  • Catalog: mTOR
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 513.0±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 264.0±32.9 °C

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

PI3K/mTOR Inhibitor-2

PI3K/mTOR Inhibitor-2 is a potent dual pan-PI3K/mTOR inhibitor with IC50s of 3.4/34/16/1 nM for PI3Kα/PI3Kβ/PI3Kδ/PI3Kγ and 4.7 nM for mTOR[1]. Antitumor activity[1].

  • CAS Number: 1848242-58-9
  • MF: C20H13ClF2N4O4S
  • MW: 478.86
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

LAS191954

LAS191954 is a potent, selective and orally active PI3Kδ inhibitor for inflammatory diseases treatment, with an IC50 of 2.6 nM[1].

  • CAS Number: 1403947-26-1
  • MF: C20H15N9O
  • MW: 397.393
  • Catalog: PI3K
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 769.0±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 418.9±35.7 °C

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

AKT-IN-6

AKT-IN-6 (Example 13) is a potent Akt inhibitor. AKT-IN-6 inhibits Akt1, Akt2 and Akt3 with IC50s < 500nM, respectively. (patent WO2013056015A1).

  • CAS Number: 1430056-54-4
  • MF: C22H20FN5O
  • MW: 389.426
  • Catalog: Akt
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 662.5±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 354.5±31.5 °C

Rheb inhibitor NR1

Rheb inhibitor NR1 is a small molecule that binds Rheb in the switch II domain (IC50=2.1 uM, Kd=1.5 uM) and selectively blocks mTORC1 signaling, potently inhibits mTORC1 driven phosphorylation of S6K1 but does not inhibit phosphorylation of AKT or ERK; in contrast to rapamycin, NR1 does not cause inhibition of mTORC2 upon prolonged treatment, potently and selectively inhibits mTORC1 in mouse kidney and muscle in vivo.

  • CAS Number: 2216763-38-9
  • MF: C25H19BrCl2N2O3S
  • MW: 578.302
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3hoi-ba-01

3HOI-BA-01 is a mammalian targeting effective rapamycin activation inhibitor.

  • CAS Number: 355428-84-1
  • MF: C19H15NO5
  • MW: 337.331
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L-Leucine-1-13C,15N

L-Leucine-1-13C,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: 80134-83-4
  • MF: C513CH1315NO2
  • MW: 133.15900
  • Catalog: mTOR
  • Density: 1.035 g/cm3
  • Boiling Point: N/A
  • Melting Point: >300ºC(lit.)
  • 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

PI3K/Akt/mTOR-IN-3

PI3K/Akt/mTOR-IN-3 (compound 3d) is a potent PI3K/AKT/mTOR inhibitor. PI3K/Akt/mTOR-IN-3 displays the inhibitory activity in MCF-7, HeLa and HepG2 cells, with IC50 values of 0.77, 1.23, and 4.57μM, respectively. PI3K/Akt/mTOR-IN-3 inhibits the migration of MCF-7 and HeLa cells at the concentration of 4 μM. PI3K/Akt/mTOR-IN-3 induces cell apoptosis and S phase arrest[1].

  • CAS Number: 2457245-94-0
  • MF: C34H51NO2
  • MW: 505.77
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A