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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Uprosertib

Uprosertib (GSK2141795) is a potent and selective pan-Akt inhibitor with IC50 values of 180/328/38 nM for Akt1/Akt2/Akt3, respectively.

  • CAS Number: 1047634-65-0
  • MF: C18H16Cl2F2N4O2
  • MW: 429.24800
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NSC45586 free base

NSC45586 free base (NCS 45586, NCI45586) is a potent, specific PHLPP2 inhibitor with IC50 of 4 uM, targets the PHLPP2 PP2C domain, suppresses MYC and triggers cell death.

  • CAS Number: 739301-85-0
  • MF: C20H18N6O3
  • MW: 390.403
  • Catalog: Ser/Thr Protease
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Indirubin-3'-monoxime-5-sulphonic acid

Indirubin-3'-monoxime-5-sulphonic acid is a potent and selective inhibitor of CDK1, CDK5, and GSK-3β with IC50s of 5 nM, 7 nM, and 80 nM, respectively[1].

  • CAS Number: 331467-05-1
  • MF: C16H11N3O5S
  • MW: 357.34
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AKT-IN-8

AKT-IN-8 is a potent AKT inhibitor with IC50s of 4.46, 2.44, and 9.47 nM for AKT1, AKT2, and AKT3, respectively[1].

  • CAS Number: 2654026-13-6
  • MF: C22H25ClN6O3
  • MW: 456.93
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

T-00127-HEV1

T-00127_HEV1 is a phosphatidylinositol 4-kinase III beta (PI4KB) inhibitor with an IC50 of 60 nM.

  • CAS Number: 900874-91-1
  • MF: C22H29N5O3
  • MW: 411.497
  • Catalog: PI4K
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AG-205

(rac)-AG-205 is a potent inhibitor of progesterone receptor membrane component 1 (Pgrmc1) that induces genes involved in sterol synthesis, including the INSIG1 protein, which forms a complex with PGRMC1. (rac)-AG-205 prevents neuronal resistance to hypoxic ischaemia by blocking NF-kB signalling and activation of the BDNF/PI3K/AKT pathway[1].

  • CAS Number: 442656-02-2
  • MF: C22H23ClN6OS
  • MW: 454.97600
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dorsomorphin dihydrochloride

Dorsomorphin dihydrochloride (BML-275 dihydrochloride) is a potent, selective and ATP-competitive AMPK inhibitor, with a Ki of 109±16 nM.

  • CAS Number: 1219168-18-9
  • MF: C24H27Cl2N5O
  • MW: 472.410
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AL-9

AL-9 is a small molecule HCV replication inhibitor with EC50 of 0.29 and 0.75 uM for genotype 1b and 2a, inhibits purified PI4KIIIα with IC50 of 0.57 uM; inhibits HCV across different genotypes with activity in the sub-micromolar to low micromolar range in the absence of significant cytotoxic effects; inhibits PI4KIIIα also in living cells, while not appreciably affecting the activity of PI4KIIIβ, does not affect the level of PI4P in the Golgi membrane.

  • CAS Number: 869218-90-6
  • MF: C23H22N4O3
  • MW: 402.454
  • Catalog: HCV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Scutellarin

Scutellarin, an active flavone isolated from Scutellaria baicalensis, can down-regulates the STAT3/Girdin/Akt signaling in HCC cells, and inhibits RANKL-mediated MAPK and NF-κB signaling pathway in osteoclasts.

  • CAS Number: 27740-01-8
  • MF: C21H18O12
  • MW: 462.360
  • Catalog: STAT
  • Density: 1.8±0.1 g/cm3
  • Boiling Point: 891.6±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 314.9±27.8 °C

Doxorubicin hydrochloride

Doxorubicin is a cytotoxic anthracycline antibiotic for the treatment of multiple cancers. The possible mechanisms by which doxorubicin acts in the cancer cell are intercalation into DNA and disruption of topoisomerase-II-mediated DNA repair.

  • CAS Number: 23214-92-8
  • MF: C27H29NO11
  • MW: 543.52
  • Catalog: Bacterial
  • Density: 1.61 g/cm3
  • Boiling Point: N/A
  • Melting Point: 205ºC
  • Flash Point: 443.8ºC

SAR-405

SAR405 is a PIK3C3/Vps34 inhibitor with an IC50 of 1.2 nM. SAR405 prevents autophagy and synergizes with MTOR inhibition in tumor cells.

  • CAS Number: 1523406-39-4
  • MF: C19H21ClF3N5O2
  • MW: 443.850
  • Catalog: Autophagy
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 526.5±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 272.2±32.9 °C

Compound 401

Compound 401 is a synthetic inhibitor of DNA-PK (IC50 = 0.28 μM) that also targets mTOR but not PI3K in vitro.

  • CAS Number: 168425-64-7
  • MF: C16H15N3O2
  • MW: 281.309
  • Catalog: DNA-PK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 456.9±55.0 °C at 760 mmHg
  • Melting Point: 214 °C
  • Flash Point: 230.1±31.5 °C

5-Iodo-indirubin-3'-monoxime

5-Iodo-indirubin-3'-monoxime is a potent GSK-3β, CDK5/P25 and CDK1/cyclin B inhibitor, competing with ATP for binding to the catalytic site of the kinase, with IC50s of 9, 20 and 25 nM, respectively[1].

  • CAS Number: 331467-03-9
  • MF: C16H10IN3O2
  • MW: 403.17
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SB203580

SB 203580 is a widely used p38 MAPK inhibitor with an IC50 of 0.3-0.5 μM. It shows more than 100-fold selectivity over PKB, LCK, and GSK-3β.

  • CAS Number: 152121-47-6
  • MF: C21H16FN3OS
  • MW: 377.435
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 615.6±55.0 °C at 760 mmHg
  • Melting Point: 249 - 250ºC
  • Flash Point: 326.1±31.5 °C

Pi3kd/v-in-01

PI3KD/V-IN-01 is a potent ATP-competitive PI3Kδ/Vps34 dual inhibitor.

  • CAS Number: 1807551-44-5
  • MF: C21H24ClN5O3S2
  • MW: 494.03
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK2126458(GSK458)

Omipalisib (GSK2126458) is a highly selective and potent inhibitor of PI3K with Kis of 0.019 nM/0.13 nM/0.024 nM/0.06 nM and 0.18 nM/0.3 nM for p110α/β/δ/γ, mTORC1/2, respectively.

  • CAS Number: 1086062-66-9
  • MF: C25H17F2N5O3S
  • MW: 505.496
  • Catalog: mTOR
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 715.6±70.0 °C at 760 mmHg
  • Melting Point: 187-189℃
  • Flash Point: 386.6±35.7 °C

MHY-1685

MHY-1685, a novel mammalian target of rapamycin (mTOR) inhibitor, provides opportunities to improve hCSC-based myocardial regeneration.

  • CAS Number: 27406-31-1
  • MF: C11H8N2O4
  • MW: 232.19
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DNA-PK-IN-7

DNA-PK-IN-7 is a potent DNA-PK inhibitor with an IC50 of 1 nM (WO2021104277A1, compound 5)[1].

  • CAS Number: 2646592-18-7
  • MF: C19H21N9O2
  • MW: 407.43
  • Catalog: DNA-PK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Vevorisertib

Vevorisertib (ARQ 751) 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, 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].

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

Multi-kinase-IN-2

Multi-kinase-IN-2 (compound 7h) is an orally active and potent angiokinase inhibitor. Multi-kinase-IN-2 exhibits excellent inhibitory activity against angiokinases including VEGFR-1/2/3, PDGFRα/β, and FGFR-1, as well as LYN and c-KIT kinases. Multi-kinase-IN-2 significantly attenuates phosphorylation of AKT and ERK proteins. Multi-kinase-IN-2 induces cell apoptosis. Multi-kinase-IN-2 shows anticancer activity[1].

  • CAS Number: 2095628-21-8
  • MF: C34H35N5O3
  • MW: 561.67
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

VX-984

VX-984 (M9831) is a selective DNA-dependent protein kinase (DNA-PK) inhibitor with IC50 of 88±64 nM for A549 lung cancer cells.

  • CAS Number: 1562396-65-9
  • MF: C22H19D2N7O
  • MW: 401.46
  • Catalog: DNA-PK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Hu7691

Hu7691 is an orally active, selective Akt inhibitor with IC50s of 4.0 nM, 97.5 nM, 28 nM for Akt1, Akt2 and Akt3, respectively. Hu7691 inhibits tumor growth and enables decrease of cutaneous toxicity in mice[1].

  • CAS Number: 2360523-76-6
  • MF: C22H22ClF3N4O
  • MW: 450.88
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK251

GSK251 is a highly potent, highly selective, orally bioavailable inhibitor of PI3Kδ with a novel binding mode.

  • CAS Number: 2125968-05-8
  • MF: C29H37FN6O4S
  • MW: 584.71
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Chaetominine

Chaetominine is an alkaloidal metabolite. Chaetominine has cytotoxicity against human leukemia K562 and colon cancer SW1116 cell lines. Chaetominine reduces MRP1-mediated drug resistance via inhibiting PI3K/Akt/Nrf2 signaling pathway in K562/Adr human leukemia cells[1][2].

  • CAS Number: 918659-56-0
  • MF: C22H18N4O4
  • MW: 402.40
  • Catalog: Keap1-Nrf2
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 720.7±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 389.6±35.7 °C

PI4KIIIbeta-IN-9

PI4KIIIbeta-IN-9 is a potent PI4KIIIβ inhibitor with an IC50 of 7 nM. PI4KIIIbeta-IN-9 also inhibits PI3Kδ and PI3Kγ with IC50s of 152 nM and 1046 nM, respectively.

  • CAS Number: 1429624-84-9
  • MF: C23H25N3O5S2
  • MW: 487.592
  • Catalog: PI4K
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

10-DEBC hydrochloride

10-DEBC hydrochloride is a selective Akt inhibitor, with an IC50 of 1.28 μM. 10-DEBC hydrochloride is a novel anti-TB compound[1][2].

  • CAS Number: 925681-41-0
  • MF: C20H26Cl2N2O
  • MW: 381.34
  • Catalog: Bacterial
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3F8

3F8 is a potent and selective GSK-3β inhibitor that could be useful as new reagent and potential therapeutic candidate for GSK3 related diseases[1].

  • CAS Number: 159109-11-2
  • MF: C15H14N2O4
  • MW: 286.28300
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PIK-75 HCl

PIK-75 is a DNA-PK and PI3K inhibitor, which inhibits DNA-PK, p110α and p110γ with IC50s of 2, 5.8 and 76 nM, respectively. PIK-75 inhibits p110α >200-fold more potently than p110β (IC50=1.3 μM).

  • CAS Number: 372196-77-5
  • MF: C16H15BrClN5O4S
  • MW: 488.74
  • Catalog: DNA-PK
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

8-Aminoadenosine

8-Aminoadenosine (8-NH2-Ado), a RNA-directed nucleoside analogue, reduces cellular ATP levels and inhibits mRNA synthesis. 8-Aminoadenosine blocks Akt/mTOR signaling and induces autophagy and apoptosis in a p53-independent manner. 8-Aminoadenosine has antitumor activity[1][2][3].

  • CAS Number: 3868-33-5
  • MF: C10H14N6O4
  • MW: 282.26
  • Catalog: Apoptosis
  • Density: 2.25g/cm3
  • Boiling Point: 747.1ºC at 760mmHg
  • Melting Point: 180-185ºC dec.
  • Flash Point: 405.6ºC

1,3-Dicaffeoylquinic acid

1,3-Dicaffeoylquinic acid is a caffeoylquinic acid derivative that exhibits antioxidant activity and radical scavenging activity.

  • CAS Number: 19870-46-3
  • MF: C25H24O12
  • MW: 516.451
  • Catalog: Akt
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 819.9±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 278.1±27.8 °C