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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ATR-IN-19

ATR-IN-19 (Compound 15 R-configure) is an ATR inhibitor[1].

  • CAS Number: 2648989-61-9
  • MF: C18H19N7OS
  • MW: 381.45
  • Catalog: ATM/ATR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HDAC-IN-43

HDAC-IN-43 is a potent HDAC 1/3/6 inhibitor with IC50 values of 82, 45, and 24 nM, respectively. HDAC-IN-43 is a weak PI3K/mTOR inhibitors with IC50 values of 3.6 and 3.7 μM, respectively. HDAC-IN-43 shows broad anti-proliferative activity [1].

  • CAS Number: 1809163-24-3
  • MF: C22H28N6O4
  • MW: 440.50
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

6-[4-(1-Aminocyclobutyl)phenyl]-5-phenyl-3-pyridinecarboxamide

AKT-IN-1 is an allosteric AKT inhibitor with an IC50 of 1.042 μM.

  • CAS Number: 1357158-81-6
  • MF: C22H21N3O
  • MW: 343.422
  • Catalog: Akt
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 496.4±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 254.0±28.7 °C

KU 59403

KU 59403 is a potent ATM inhibitor, with an IC50 of 3 nM.

  • CAS Number: 845932-30-1
  • MF: C29H32N4O4S2
  • MW: 564.719
  • Catalog: ATM/ATR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 814.3±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 446.3±34.3 °C

FRATtide

FRATtide is a peptide derived from the GSK-3 binding protein that inhibits the phosphorylation of Axin and β-catenin. FRATtide inhibits GSK-3 binding to Axin[1].

  • CAS Number: 251087-38-4
  • MF: C192H327N67O60
  • MW:
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI3K/mTOR Inhibitor-4

PI3K/mTOR Inhibitor-4 is an orally active pan-class I PI3K/mTOR inhibitor. PI3K/mTOR Inhibitor-4 has enzymatic inhibition activity for PI3Kα, PI3Kγ, PI3Kδ and mTOR with IC50 values of 0.63 nM, 22 nM, 9.2 nM and 13.85 nM, respectively. PI3K/mTOR Inhibitor-4 can be used for the research of cancer[1].

  • CAS Number: 2361215-32-7
  • MF: C27H22FN3O6S
  • MW: 535.54
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Kahweol

Kahweol is one of the consituents of the coffee from Coffea Arabica with anti-inflammatory anti-angiogenic, and anti-cancerous activities. Kahweol inhibits adipogenesis and increase glucose uptake by AMP-activated protein kinase (AMPK) activation. Kahweol induces apoptosis.

  • CAS Number: 6894-43-5
  • MF: C20H26O3
  • MW: 314.419
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 476.6±45.0 °C at 760 mmHg
  • Melting Point: 88-90 °C
  • Flash Point: 242.0±28.7 °C

GSK2646264

GSK2646264 (Compound 44) is a potent and selective spleen tyrosine kinase (SYK) inhibitor with a pIC50 of 7.1. GSK2646264 also inhibits other kinases with pIC50 values of 5.4, 5.4, 5.3, 5, 4.5, <4.6 and <4.3 against LCK, LRRK2, GSK3β, JAK2, VEGFR2, Aurora B and Aurora A, respectively. GSK2646264 is penetrable into the epidermis and dermis of the skin[1].

  • CAS Number: 1398695-47-0
  • MF: C24H26N2O2
  • MW: 374.48
  • Catalog: LRRK2
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 517.4±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 266.7±30.1 °C

Mytoxin B

Mytoxin B is an ADC cytotoxin. Mytoxin B is a satratoxin-type trichothecene macrolide and is similar to the effect of LY294002 (HY-10108). Mytoxin B induces cell apoptosis via PI3K/Akt pathway[1].

  • CAS Number: 105049-15-8
  • MF: C29H36O9
  • MW: 528.59100
  • Catalog: ADC Cytotoxin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

IQZ23

IQZ23 inhibits adipocyte differentiation via AMPK pathway activation. IQZ23 exerts a high efficacy in decreasing the triglyceride level (EC50=0.033 μM) in 3T3-L1 adipocytes. IQZ23 could be used for the research of obesity and related metabolic disorders[1].

  • CAS Number: 2415643-79-5
  • MF: C26H29N5O2
  • MW: 443.54
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SHP2-IN-8

SHP2-IN-8 is a highly potent, selective, and cellularly active allosteric SHP2 inhibitor with IC50 value of 23 nM and Ki of 22 nM. SHP2-IN-8 is reversible and noncompetitive. SHP2-IN-8 causes a significant thermal shift with the ΔTm of 7.01 ℃. SHP2-IN-8 induces the apoptosis and inhibits the phosphorylation of AKT in Hela cells[1].

  • CAS Number: 1801692-60-3
  • MF: C17H21Cl2N5S
  • MW: 398.35
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Di-n-Amyl phthalate

Dipentyl phthalate is an endocrine-disrupting phthalate plasticizer. Dipentyl phthalate increases AMPK phosphorylation and decreases AKT1 phosphorylation and SIRT1 levels. Dipentyl phthalate reduces adrenocorticotropic hormone levels. Dipentyl phthalate is a testicular toxicant[1].

  • CAS Number: 131-18-0
  • MF: C18H26O4
  • MW: 306.40
  • Catalog: AMPK
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 357.0±10.0 °C at 760 mmHg
  • Melting Point: -55ºC
  • Flash Point: 188.8±8.5 °C

PI3KC2α-IN-3

PI3KC2α-IN-3 is a potent and highly selective PI3KC2α inhibitor (IC50: 126 nM). PI3KC2α-IN-3 interacts with the ATP-binding site of PI3KC2α. PI3KC2α-IN-3 impairs endocytic membrane dynamics and membrane remodeling. PI3KC2α-IN-3 can be used in the research of thrombosis, diabetes and cancers[1].

  • CAS Number: 2397679-88-6
  • MF: C26H23N7O4S3
  • MW: 593.70
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AZD-7648

AZD-7648 is a potent and selective DNA-PK inhibitor. Anti-tumour activity[1].

  • CAS Number: 2230820-11-6
  • MF: C18H20N8O2
  • MW: 380.40
  • Catalog: DNA-PK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cyclovirobuxine

Cyclovirobuxine D (CVB-D) is the main active component of the traditional Chinese medicine Buxus microphylla. Cyclovirobuxine D induces autophagy and attenuates the phosphorylation of Akt and mTOR[1]. Cyclovirobuxine D inhibits cell proliferation of gastric cancer cells through suppression of cell cycle progression and inducement of mitochondria-mediated apoptosis[2]. Cyclovirobuxine D is beneficial for heart failure induced by myocardial infarction[3].

  • CAS Number: 860-79-7
  • MF: C26H46N2O
  • MW: 402.656
  • Catalog: Apoptosis
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 495.7±10.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 34.1±9.6 °C

mTORC1-IN-2

mTORC1-IN-2 (compound H3) is a NO donor compound that alleviates vasodilation and attenuates myocardial hypoxic injury. mTORC1-IN-2 upregulates TSC2-P expression and inhibits mTORC1 expression[1].

  • CAS Number: 2974368-96-0
  • MF: C16H15N3O6
  • MW: 345.31
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BQR-695

BQR-695 is a PI4KIIIβ inhibitor with IC50s of 80 and 3.5 nM for human PI4KIIIβ and Plasmodium variant of PI4KIIIβ, respectively.

  • CAS Number: 1513879-21-4
  • MF: C19H20N4O3
  • MW: 352.39
  • Catalog: PI4K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI3KC2α-IN-1

PI3KC2α-IN-1 is a potent PI3KC2α inhibitor (IC50: 95 nM). PI3KC2α-IN-1 interacts with the ATP-binding site of PI3KC2α. PI3KC2α-IN-1 can be used in the research of thrombosis, diabetes and cancers[1].

  • CAS Number: 2397679-87-5
  • MF: C19H16N6O2S2
  • MW: 424.50
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI3K-IN-19 hydrochloride

PI3K-IN-19 hydrochloride is a phosphotidylinositol-3-kinase (PI3K) inhibitor extracted from patent WO2017153220, step 5[1].

  • CAS Number: 2132943-80-5
  • MF: C23H27ClN8O5
  • MW: 530.96
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Akt3 degrader 1

Akt3 degrader 1 (compound 12l) is a selective Akt3 degrader that overcomes Osimertinib (HY-15772)-induced resistance in H1975OR NSCLC cells. Akt3 degrader 1 also has anti-proliferative activity and significantly inhibits tumour growth in mice. Akt3 degrader 1 can be used in the study of drug-resistant non-small cell lung cancer[1].

  • CAS Number: 2836342-69-7
  • MF: C53H72N8O4
  • MW: 885.19
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Indirubin-3′-oxime

Indirubin-3′-oxime (IDR3O), a synthetic derivative of indirubin, is a potent inhibitor of cyclin-dependent kinases (CDKs) and glycogen synthase kinase 3β (GSK3β). Indirubin-3′-oxime directly inhibits the activity of all three isoforms of JNK (JNK1, JNK2, and JNK3), with IC50s of 0.8 μM, 1.4 μM, and 1.0 μM, respectively. Indirubin-3′-oxime can enhance height growth via activation of Wnt/β-catenin signaling in chondrocytes[1][2][3].

  • CAS Number: 667463-82-3
  • MF: C16H11N3O2
  • MW: 277.28
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sennidin A

Sennidin A, isolated from the leaves of Cassia angustifolia, 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: 641-12-3
  • 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

AMPK activator 991

AMPK activator 991 is an allosteric AMPK activator, activates non-phosphorylated Thr172 AMPK in vitro binds to α1β1γ1 and α2β1γ1 with Kd of 0.13 and 0.17 uM, respectively.

  • CAS Number: 1219739-95-3
  • MF: C24H18ClN3O3
  • MW: 431.876
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK3-IN-3

GSK3-IN-3 is a mitophagy inducer, inducing Parkin-dependent mitophagy. GSK3-IN-3 is also a GSK-3 inhibitor with an IC50 value of 3.01 μM. GSK3-IN-3 is non-ATP nor substrate competitive and is neuroprotective against 6-OHDA[1][2][3].

  • CAS Number: 331963-27-0
  • MF: C24H35N3O4
  • MW: 429.55
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NU7441 (KU-57788)

KU-57788 is a potent and selective inhibitor of DNA-PK with an IC50 of 13 nM, with selectivity over a range of kinases including mTOR, PI 3-K, ATM and ATR.

  • CAS Number: 503468-95-9
  • MF: C25H19NO3S
  • MW: 413.488
  • Catalog: CRISPR/Cas9
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 646.9±55.0 °C at 760 mmHg
  • Melting Point: 246.28° C
  • Flash Point: 345.0±31.5 °C

Leniolisib phosphate

Leniolisib (CDZ173) phosphate is a potent and selective PI3Kδ inhibitor. Leniolisib phosphate has the potential for immunodeficiency disorders treatment.

  • CAS Number: 1354691-97-6
  • MF: C21H28F3N6O6P
  • MW: 548.45
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Elimusertib (BAY-1895344) hydrochloride

BAY-1895344 is a potent, orally available and selective ATR inhibitor, with IC50 of 7 nM. Anti-tumor activity[1].

  • CAS Number: 1876467-74-1
  • MF: C20H22ClN7O
  • MW: 411.89
  • Catalog: ATM/ATR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Rapamycin-d3

Rapamycin-d3 (Sirolimus-d3) is the deuterium labeled Rapamycin. Rapamycin is a potent and specific mTOR inhibitor with an IC50of 0.1 nM in HEK293 cells. Rapamycin binds to FKBP12 and specifically acts as an allosteric inhibitor of mTORC1[1]. Rapamycin is an autophagy activator, an immunosuppressant[2].

  • CAS Number: 392711-19-2
  • MF: C51H76D3NO13
  • MW: 917.19000
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

P110δ-IN-1

P110δ-IN-1 is a potent and selective inhibitor of P110δ extracted from patent WO 2014055647 A1, with an IC50 of 8.4 nM[1].

  • CAS Number: 1595129-71-7
  • MF: C31H40N8O3S
  • MW: 604.77
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BX-912

BX-912 is a potent PDK1 inhibitors with an IC50 of 12 nM.

  • CAS Number: 702674-56-4
  • MF: C20H23BrN8O
  • MW: 471.354
  • Catalog: PDK-1
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A