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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Quercetin (hydrate)

Quercetin hydrate, a natural flavonoid, is a stimulator of recombinant SIRT1 and also a PI3K inhibitor with IC50 of 2.4 μM, 3.0 μM and 5.4 μM for PI3K γ, PI3K δ and PI3K β, respectively[1].

  • CAS Number: 849061-97-8
  • MF: C15H10O7.x H2O
  • MW: 320.251
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: 714.6ºC at 760 mmHg
  • Melting Point: >300ºC
  • Flash Point: 386ºC

dorsomorphin

Dorsomorphin is a potent and selective AMPK inhibitor, that is competitive with ATP, with Ki=109±16 nM in the absence of AMP.

  • CAS Number: 866405-64-3
  • MF: C24H25N5O
  • MW: 399.488
  • Catalog: Autophagy
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PP2A Cancerous-IN-1

PP2A Cancerous-IN-1 is a strong and potent CIP2A (Cancerous inhibitor of PP2A) and p-Akt inhibitor. PP2A Cancerous-IN-1 shows the most potent antiproliferative activities[1].

  • CAS Number: 1403933-79-8
  • MF: C30H24N4O3
  • MW: 488.54
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L-(3,3-2H2)Leucine

L-Leucine-d2 is the deuterium labeled L-Leucine. L-Leucine is an essential branched-chain amino acid (BCAA), which activates the mTOR signaling pathway[1].

  • CAS Number: 362049-59-0
  • MF: C6H11D2NO2
  • MW: 133.185
  • Catalog: mTOR
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 225.8±23.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 90.3±22.6 °C

Arnicolide D

Arnicolide D is a sesquiterpene lactone isolated from Centipeda minima. Arnicolide D modulates the cell cycle, activates the caspase signaling pathway and inhibits the PI3K/AKT/mTOR and STAT3 signaling pathways. Arnicolide D inhibits Nasopharyngeal carcinoma (NPC) cell viability in a concentration- and time-dependent manner[1].

  • CAS Number: 34532-68-8
  • MF: C19H24O5
  • MW: 332.39100
  • Catalog: Caspase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SOLENOPSIN

Solenopsin is an ATP-competitive AKT inhibitor with IC50 value of 10 μM .

  • CAS Number: 137038-57-4
  • MF: C17H35N
  • MW: 253.46600
  • Catalog: Akt
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Buformin

Buformin (1-Butylbiguanide) is a potent and orally active biguanide antidiabetic agent, an AMPK activator. Buformin decreases hepatic gluconeogenesis and lowers blood glucose production in vivo. Buformin also has anti-cancer activities and is applied in cancer study (such as, cervical cancer and breast cancer, et al)[1].

  • CAS Number: 692-13-7
  • MF: C6H15N5
  • MW: 157.21700
  • Catalog: AMPK
  • Density: 1.22g/cm3
  • Boiling Point: 322.7ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 148.9ºC

Polyphyllin D

Polyphyllin I is a bioactive constituent extracted from Paris polyphylla, has strong anti-tumor activity. Polyphyllin I is an activator of the JNK signaling pathway and is an inhibitor of PDK1/Akt/mTOR signaling. Polyphyllin I induces autophagy, G2/M phase arrest and apoptosis[1][2][3].

  • CAS Number: 50773-41-6
  • MF: C44H70O16
  • MW: 855.017
  • Catalog: Apoptosis
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MMV-390048

MMV390048 is a representative of a new chemical class of Plasmodium PI4K inhibitor (Kdapp=0.3 µM). MMV390048 binds to the ATP binding site of Plasmodium PI4K and does not bind to other P. falciparum and human kinases apart from human PIP4K2C, thus alleviating potential kinase-mediated safety concerns. MMV390048 is an antimalarial agent[1].

  • CAS Number: 1314883-11-8
  • MF: C18H14F3N3O2S
  • MW: 393.383
  • Catalog: Parasite
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 534.4±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 277.0±30.1 °C

Vistusertib (AZD2014)

Vistusertib (AZD2014) is an ATP competitive mTOR inhibitor with an IC50 of 2.81 nM. AZD2014 inhibits both mTORC1 and mTORC2 complexes.

  • CAS Number: 1009298-59-2
  • MF: C25H30N6O3
  • MW: 462.544
  • Catalog: Autophagy
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ATM-IN-1

ATM-IN-1 is a potent inhibitor of ATM. ATM is located mainly in the nucleus and microsomes and is involved in cell cycle progression and in the cell cycle checkpoint response to DNA damage. ATM-IN-1 has the potential for the research of cancer and neurology diseases (extracted from patent WO2021139814A1, compound 3)[1].

  • CAS Number: 2662761-76-2
  • MF: C30H36N6O3
  • MW: 528.65
  • Catalog: ATM/ATR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PARP/PI3K-IN-1

PARP/PI3K-IN-1 (compound 15) is a potent PARP/PI3K inhibitor with pIC50 values of 8.22, 8.44, 8.25, 6.54, 8.13, 6.08 for PARP-1, PARP-2, PI3Kα, PI3Kβ, PI3Kδ, and PI3Kγ, respectively. PARP/PI3K-IN-1 is a highly effective anticancer compound targeted against a wide range of oncologic diseases[1].

  • CAS Number: 2337386-47-5
  • MF: C33H28F4N8O3
  • MW: 660.62
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI 828

PI-828 is a dual PI3K and casein kinase 2 (CK2) inhibitor with IC50s of 173 nM, 149 nM, and 1127 nM for p110α, CK2, and CK2α2 in lipid kinase assay, respectively[1].

  • CAS Number: 942289-87-4
  • MF: C19H18N2O3
  • MW: 322.35800
  • Catalog: PI3K
  • Density: 1.316g/cm3
  • Boiling Point: 534.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 276.9ºC

NIBR-17

NIBR-17 is a pan-class I PI3K inhibitor with suitable pharmacokinetic properties and inhibits tumor growth[1].

  • CAS Number: 944396-88-7
  • MF: C18H20N8O2
  • MW: 380.40
  • Catalog: PI3K
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 718.3±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 388.2±35.7 °C

PI3K-IN-36

PI3K-IN-36 (compound A36) is a potent PI3K inhibitor. PI3K-IN-36 can be used in research of follicular lymphoma (FL)[1].

  • CAS Number: 1401436-93-8
  • MF: C30H36F2N8O
  • MW: 562.66
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Guggulsterone E&Z

Guggulsterone is a plant sterol derived from the gum resin of the tree Commiphora wightii. Guggulsterone inhibits the growth of a wide variety of tumor cells and induces apoptosis through down regulation of antiapoptotic gene products (IAP1, xIAP, Bfl-1/A1, Bcl-2, cFLIP and survivin), modulation of cell cycle proteins (cyclin D1 and c-Myc), activation of caspases and JNK, inhibition of Akt[1]. Guggulsterone, a farnesoid X receptor (FXR) antagonist, decreases CDCA-induced FXR activation with IC50s of 17 and 15 μM for Z- and E-Guggulsterone, respectively[2].

  • CAS Number: 95975-55-6
  • MF: C21H28O2
  • MW: 312.446
  • Catalog: Apoptosis
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 463.3±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 172.3±25.7 °C

MIPS-21335

MIPS-21335 is an PI3KC2α inhibitor (IC50: 7 nM). MIPS-21335 also inhibits PI3KC2β, p110α, p110β and p110δ (IC50: 0.043, 0.140, 0.386, 0.742 μM). MIPS-21335 has antithrombotic effect[1].

  • CAS Number: 2569296-51-9
  • MF: C24H21N7O5
  • MW: 487.47
  • Catalog: PI4K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CGS 15943

CGS 15943 is an adenosine A2 receptor antagonist and reduces stroke injury in the Mongolian gerbil[1]. CGS 15943 is a selectively p110γ inhibitor with an IC50 of 1.1 μM, shows inhibitory effect on p110δ (IC50=8.47 μM), has an anti-carcinogenic effect on HCC and PDAC cells[2].

  • CAS Number: 104615-18-1
  • MF: C13H8ClN5O
  • MW: 285.68900
  • Catalog: Adenosine Receptor
  • Density: 1.72 g/cm3
  • Boiling Point: 566.6ºC at 760 mmHg
  • Melting Point: 278-279 °C
  • Flash Point: 296.5ºC

PI3Kα-IN-9

PI3Kα-IN-9 (compound 27) is a selective, long-acting and oral active PI3Kα inhibitor with IC50 values of 4.4, 128, 146 and 153 nM for PI3Kα, PI3Kγ, PI3Kδ and PI3Kβ, respectively. PI3Kα-IN-9 has antiproliferative activity and induces apoptosis. PI3Kα-IN-9 can be used for cancer research[1].

  • CAS Number: 2715287-67-3
  • MF: C18H21N7O3
  • MW: 383.40
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cimigenol-3-O-alpha-L-arabinoside

Cimiracemoside C is an active component of Cimicifuga racemosa, activates AMPK, has the potential activity against diabetes[1].

  • CAS Number: 256925-92-5
  • MF: C35H56O9
  • MW: 620.814
  • Catalog: AMPK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 740.3±60.0 °C at 760 mmHg
  • Melting Point: 258-260℃
  • Flash Point: 401.5±32.9 °C

GDC-0068

Ipatasertib (GDC-0068) is a highly selective and ATP-competitive pan-Akt inhibitor with IC50s of 5, 18 and 8 nM for Akt1, Akt2 and Akt3, respectively.

  • CAS Number: 1001264-89-6
  • MF: C24H32ClN5O2
  • MW: 457.996
  • Catalog: Akt
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 669.4±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 358.7±31.5 °C

SKLB-197

SKLB-197 showed an IC50 value of 0.013 μM against ATR but very weak or no activity against other 402 protein kinases. It displayed potent antitumor activity against ATM-deficent tumors both in vitro and in vivo.

  • CAS Number: 2713577-16-1
  • MF: C25H24N6O
  • MW: 424.50
  • Catalog: ATM/ATR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Zandelisib

Zandelisib is a phosphatidylinositol 3-kinase (PI3K) inhibitor extracted from patent WO2019183226 A1, Compound Example 1. Zandelisib selectively inhibits p110δ with an IC50 of 3.5 nM. Zandelisib functions as an antineoplastic[1][2].

  • CAS Number: 1401436-95-0
  • MF: C31H38F2N8O
  • MW: 576.68
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: 729.2±70.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

BI-1622

BI-1622 is an orally active, potent and highly selective HER2 (ERBB2) inhibitor, with an IC50 of 7 nM. BI-1622 shows greater than 25-fold selectivity over EGFR. BI-1622 shows high antitumor efficacy in vivo in xenograft mouse tumor models with engineered H2170 and PC9 cells and had a favorable drug metabolism and pharmacokinetics profile[1].

  • CAS Number: 2681392-19-6
  • MF: C26H24N10O2
  • MW: 508.53
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

3-Methyladenine-d3

3-Methyladenine-d3 is the deuterium labeled 3-Methyladenine[1]. 3-Methyladenine (3-MA) is a PI3K inhibitor. 3-Methyladenine is a widely used inhibitor of autophagy via its inhibitory effect on class III PI3K[2].

  • CAS Number: 110953-39-4
  • MF: C6H4D3N5
  • MW: 152.17200
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pomiferin

Pomiferin, a flavonoid from the fruits of Maclura pomifera, acts as an potential inhibitor of HDAC, with an IC50 of 1.05 μM, and also potently inhibits mTOR (IC50, 6.2 µM).

  • CAS Number: 572-03-2
  • MF: C25H24O6
  • MW: 420.45400
  • Catalog: HDAC
  • Density: 1.314g/cm3
  • Boiling Point: 673.5ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 233.3ºC

Alpelisib hydrochloride

Alpelisib hydrochloride (BYL-719 hydrochloride) is a potent and selective PI3Kα inhibitor with IC50s of 5 nM, 250 nM, 290 nM and 1200 nM for p110α, p110γ, p110δ, and p110β, respectively[1].

  • CAS Number: 1584128-91-5
  • MF: C19H23ClF3N5O2S
  • MW: 477.93
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI3K/mTOR Inhibitor-1

PI3K/mTOR Inhibitor-1 is a potent, orally bioavailable dual PI3K/mTOR inhibitor with IC50s of 20/376/204/46 nM and 186 nM for PI3Kα/PI3Kβ/PI3Kγ/PI3Kδ and mTOR, respectively[1]. Antitumor activity[1].

  • CAS Number: 1949802-49-6
  • MF: C18H22FN5O3S
  • MW: 407.46
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

YH-306

YH-306 is a candidate drug in preventing growth and metastasis of colorectal cancer by modulating FAK signalling pathway.

  • CAS Number: 1373764-75-0
  • MF: C19H18N2O2
  • MW: 306.36
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

7-Methoxyisoflavone

7-Methoxyisoflavone is an isoflavone derivative and also an activator of adenosine monophosphate-activated protein kinase (AMPK).

  • CAS Number: 1621-56-3
  • MF: C16H12O3
  • MW: 252.26500
  • Catalog: AMPK
  • Density: 1.24g/cm3
  • Boiling Point: 421.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 200.3ºC