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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AZD2858

AZD2858 is a potent, orally active GSK-3 inhibitor, with IC50s of 0.9 and 5 nM for GSK-3α and GSK-3β, respectively, used in the research of fracture healing.

  • CAS Number: 486424-20-8
  • MF: C21H23N7O3S
  • MW: 453.517
  • Catalog: GSK-3
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AMPK-IN-3

AMPK-IN-3 (compound 67) is a potent and selective AMPK inhibitor with IC50s of 60.7, 107 and 3820 nM for AMPK (α2), AMPK (α1) and KDR, respectively. AMPK-IN-3 inhibits AMPK does not affect cell viability or cause significant cytotoxicity in K562 cells. AMPK-IN-3 can be used in study of cancer[1].

  • CAS Number: 2417674-27-0
  • MF: C25H33N5O3
  • MW: 451.56
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MOMIPP

MOMIPP, a macropinocytosis inducer, is a PIKfyve inhibitor. MOMIPP penetrates the blood-brain barrier (BBB)[1][2].

  • CAS Number: 1363421-46-8
  • MF: C18H16N2O2
  • MW: 292.33
  • Catalog: PIKfyve
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

6-Me-ATP

6-Me-ATP (N6-Methyl-ATP) is a N6-modified ATP derivative. 6-Me-ATP shows excellent binding affinity to GSK3, serving as the phosphate group donor for GSK3β-catalyzed phosphorylation of its substrate peptide[1].

  • CAS Number: 3130-39-0
  • MF: C11H18N5O13P3
  • MW: 521.21
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sapanisertib (MLN0128)

Sapanisertib (INK-128) is a ATP-dependent mTOR1/2 inhibitor with an IC50 of 1 nM for mTOR kinase.

  • CAS Number: 1224844-38-5
  • MF: C15H15N7O
  • MW: 309.326
  • Catalog: Autophagy
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 598.8±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 315.9±32.9 °C

18bioder

18BIOder is a neuroprotective inhibitor of GSK-3β, highly selectively inhibiting HIV-1. It is the second generation derivative of 6BIO.

  • CAS Number: 275374-93-1
  • MF: C9H7ClN2O2
  • MW: 210.62
  • Catalog: HIV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MELK-8a

MELK-8a (NVS-MELK8a) is a highly potent and selective maternal embryonic leucine zipper kinase (MELK) inhibitor with IC50 of 2 nM. MELK-8a also inhibits Flt3 (ITD), Haspin, PDGFRα with IC50s of 0.18, 0.19, and 0.42 μM, respectively. MELK plays an essential role in regulating cell mitosis in a subset of cancer cells[1].

  • CAS Number: 1922153-17-0
  • MF: C25H32N6O
  • MW: 432.572
  • Catalog: MELK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI3Kγ inhibitor 7

PI3Kγ inhibitor 7 (compound 2) is a potent and orally active PI3Kγ inhibitor with IC50 values of 4768, 878.1, 3.42, 355.2 nM for PI3Kα, PI3Kβ, PI3Kγ, PI3Kδ, respectively. PI3Kγ inhibitor 7 shows antitumor activity[1].

  • CAS Number: 2575863-25-9
  • MF: C31H25N9O2
  • MW: 555.59
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK-3β inhibitor 1

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: 187325-53-7
  • MF: C14H10N2O
  • MW: 222.24
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

IITZ-01

IITZ-01 is a potent lysosomotropic autophagy inhibitor with single-agent antitumor activity, with an IC50 of 2.62 μM for PI3Kγ.

  • CAS Number: 1807988-47-1
  • MF: C26H23FN8O
  • MW: 482.51
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sophocarpine

Sophocarpine (monohydrate) is one of the significant alkaloid extracted from the traditional herb medicine Sophora flavescens which has many pharmacological properties such as anti-virus, anti-tumor, anti-inflammatory. Sophocarpine (monohydrate) significantly inhibits the growth of gastric cancer (GC) cells through multiple mechanisms such as induction of autophagy, activation of cell apoptosis and down-regulation of cell survival PI3K/AKT signaling pathway. Sophocarpine (monohydrate) has been demonstrated to have anti-tumor activity in various cancer cells, including hepatocellular carcinoma, prostate cancer and colorectal cancer[1].

  • CAS Number: 145572-44-7
  • MF: C15H22N2O
  • MW: 246.348
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 425.4±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 194.0±21.1 °C

NU5455

NU5455 is a potent, selective, and orally active inhibitor of DNA-PKcs. NU5455 administration increases both the efficacy and the toxicity of a parenterally administered topoisomerase inhibitor. NU5455 enhances the activity of Doxorubicin released locally in liver tumor xenografts without inducing any adverse effect[1].

  • CAS Number: 1257235-99-6
  • MF: C34H33N3O5S
  • MW: 595.71
  • Catalog: DNA-PK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PDK1-IN-RS2

PDK1-IN-RS2 is a mimic of peptide docking motif (PIFtide) and is a substrate-selective PDK1 inhibitor with a Kd of 9 μM. PDK1-IN-RS2 suppresses the activation of the downstream kinases S6K1 by PDK1[1].

  • CAS Number: 1643958-89-7
  • MF: C15H9ClN2O2S3
  • MW: 380.89
  • Catalog: PDK-1
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

STO-609 (acetate)

STO-609 acetate is a selective and cell-permeable inhibitor of the Ca2+/calmodulin-dependent protein kinase kinase (CaM-KK), with Ki values of 80 and 15 ng/mL for recombinant CaM-KKα and CaM-KKβ, respectively. STO-609 acetate inhibits AMP-activated protein kinase kinase (AMPKK) activity in HeLa cell lysates with an IC50 ~0.02 g/ml.

  • CAS Number: 1173022-21-3
  • MF: C21H14N2O5
  • MW: 374.35
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Foenumoside B

Foenumoside B is a triterpene saponin isolated from Lysimachia foenum-graecum. Foenumoside B activates AMPK signaling, inhibits PPARγ-induced adipogenesis, and shifts lipid metabolism toward lipolysis. Foenumoside B can be used in the study of obesity and obesity-related metabolic diseases[1].

  • CAS Number: 877661-00-2
  • MF: C60H96O25
  • MW: 1217.39
  • Catalog: PPAR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BRD3731

BRD3731 is a potent, selective GSK3β inhibitor with IC50 of 15 nM, 14-fold selectivity for GSK3β over GSK3α (IC50=215 nM); displays excellent selectivity in a penal of 311 kinases, displays reduced potency toward the GSK3β mutant (D133E) with IC50 of 53 nM; induces β-catenin stabilization starting at 20 uM in the HL-60 AML cell line, decreases β-catenin S33/37/T41 phosphorylation and induces β-catenin S675 phosphorylation, resulting in increased β-catenin.

  • CAS Number: 2056262-08-7
  • MF: C24H31N3O
  • MW: 377.532
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BIBU1361

BIBU1361 induces apoptosis and inhibits autophagy. BIBU1361 inhibits pro-survival pathways Akt/mTOR and gp130/JAK/STAT3, and decreased levels of pro-inflammatory cytokine IL-6[1].

  • CAS Number: 793726-84-8
  • MF: C22H27ClFN7
  • MW: 443.95
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: 663.5ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 355.1ºC

Merck-22-6

Akt1/Akt2-IN-2 (compound 7) is an allosteric dual Akt1 and Akt2 inhibitor (IC50=138 nM and 212 nM, respectively). Akt1/Akt2-IN-2 increases activity of caspase-3, and inhibits viability of a number of tumor cells[1].

  • CAS Number: 612847-42-4
  • MF: C40H43N7O2
  • MW: 653.81500
  • Catalog: Caspase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mirin

Mirin is a potent Mre11-Rad50-Nbs1 (MRN) complex inhibitor. Mirin prevents MRN-dependent activation of ATM (IC50=12 μM) without affecting ATM protein kinase activity, and it inhibits Mre11-associated exonuclease activity. Mirin abolishes the G2/M checkpoint and homology-dependent repair in mammalian cells. Mirin prevents ATM activation in response to DNA double-strand breaks (DSBs) and blocks homology-directed repair (HDR) in mammalian cells[1].

  • CAS Number: 299953-00-7
  • MF: C10H8N2O2S
  • MW: 220.248
  • Catalog: ATM/ATR
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 441.6±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 220.8±31.5 °C

Capivasertib (AZD5363)

Capivasertib (AZD5363) is a potent pan-AKT kinase inhibitor with IC50 of 3, 7 and 7 nM for Akt1,Akt2 and Akt3, respectively.

  • CAS Number: 1143532-39-1
  • MF: C21H25ClN6O2
  • MW: 428.915
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

bpV(phen)

bpV(phen) 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. bpV(phen) is an insulin-mimetic agent following insulin-receptor tyrosine kinase hyperphosphorylation and activation. bpV(phen) activates HIV-1 transcription and replication via NF-κB-dependent and independent mechanisms. bpV(phen) inhibits proliferation of the protozoan parasite Leishmania in vitro. bpV(phen) 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) can also induce cell apoptosis, and has anti-angiogenic and anti-tumor activity[1][2][3][4][5].

  • CAS Number: 42494-73-5
  • MF: C12H8KN2O5V
  • MW: 354.27400
  • Catalog: HIV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ubiquinone Q0

Coenzyme Q0 (CoQ0) is a potent, oral active ubiquinone compound can be derived from Antrodia cinnamomea. Coenzyme Q0 induces apoptosis and autophagy, suppresses of HER-2/AKT/mTOR signaling to potentiate the apoptosis and autophagy mechanisms. Coenzyme Q0 regulates NFκB/AP-1 activation and enhances Nrf2 stabilization in attenuation of inflammation and redox imbalance. Coenzyme Q0 has anti-angiogenic activity through downregulation of MMP-9/NF-κB and upregulation of HO-1 signaling[1][2][3].

  • CAS Number: 605-94-7
  • MF: C9H10O4
  • MW: 182.173
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 331.4±42.0 °C at 760 mmHg
  • Melting Point: 58-60 °C(lit.)
  • Flash Point: 148.6±27.9 °C

AKT-IN-9

AKT-IN-9 is a potent inhibitor of AKT. Protein kinase B (PKB, also known as AKT) is central to PI3K/AKT/mTOR signaling in cells, and its function is important for cell growth, survival, differentiation and metabolism. AKT-IN-9 has the potential for the research of breast and prostate cancer (extracted from patent WO2021185238A1, compound 1)[1].

  • CAS Number: 2709045-53-2
  • MF: C24H29ClN6O
  • MW: 452.98
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BRD3731

BRD3731 is a selective GSK3β inhibitor, with IC50s of 15 nM and 215 nM for GSK3β and GSK3α, respectively. BRD3731 can be used for the research of a mood disorder, post-traumatic stress disorder (PTSD), psychiatric disorder, diabetes, and neurodegenerative disorder[1].

  • CAS Number: 2056262-07-6
  • MF: C24H31N3O
  • MW: 377.52
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NVP-CLR457

NVP-CLR457 (compound 40) is an orally active, potent and balanced pan-class I PI3K inhibitor. NVP-CLR457 shows a clear dose-dependent PK/PD/efficacy relationship. NVP-CLR457 has antitumor activity[1].

  • CAS Number: 1453082-52-4
  • MF: C18H20F3N7O4
  • MW: 455.39
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

A-443654

A-443654 is a potent Akt1/2/3 inhbitor, with a Ki of 160 pM for Akt1.

  • CAS Number: 552325-16-3
  • MF: C24H23N5O
  • MW: 397.472
  • Catalog: Akt
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 722.0±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 390.4±32.9 °C

ATM Inhibitor-6

ATM inhibitor-6 (A-193) is a selective ATM kinase inhibitor. ATM inhibitor-6 can be used in cancer research[1].

  • CAS Number: 2765544-85-0
  • MF: C28H33FN6O2
  • MW: 504.60
  • Catalog: ATM/ATR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AT-533

AT-533 is a potent Hsp90 and HSV inhibitor. AT-533 suppresses tumor growth and angiogenesis by blocking the HIF-1α/VEGF/VEGFR-2 signaling pathway. AT-533 also inhibits the activation of the downstream pathways, including Akt/mTOR/p70S6K, Erk1/2 and FAK. AT-533 inhibits the tube formation, cell migration, and invasion of human umbilical vein endothelial cells (HUVECs)[1][2][3].

  • CAS Number: 908112-37-8
  • MF: C23H30N4O3
  • MW: 410.51
  • Catalog: HSV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AKT-IN-10

AKT-IN-10 is a potent inhibitor of AKT. Protein kinase B (PKB, also known as AKT) is central to PI3K/AKT/mTOR signaling in cells, and its function is important for cell growth, survival, differentiation and metabolism. AKT-IN-10 has the potential for the research of breast and prostate cancer (extracted from patent WO2021185238A1, compound 4)[1].

  • CAS Number: 2709045-56-5
  • MF: C26H34ClN5O2
  • MW: 484.03
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(1r,4r)-4-(((6-(1-(Cyclopropylmethyl)-2-oxo-1,2-dihydropyridin-4-yl)benzo[d]thiazol-2-yl)amino)methyl)cyclohexane-1-carboxylicacid

PI4K-IN-1 (compound 44) is a potent PI4KIII inhibitor, with pIC50 values of 9.0 and 6.6 for PI4KIIIα and PI4KIIIβ, respectively. PI4K-IN-1 also inhibits PI3Kα/β/γ/δ, with pIC50 values of 4.0/<3.7/5.0/<4.1, respectively[1].

  • CAS Number: 1800017-49-5
  • MF: C24H27N3O3S
  • MW: 437.55
  • Catalog: PI3K
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 690.9±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 371.6±34.3 °C