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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SC79

SC79 is a selective and cell-permeable Akt activator which activates Akt phosphorylation and inhibits Akt membrane translocation.

  • CAS Number: 305834-79-1
  • MF: C17H17ClN2O5
  • MW: 364.780
  • Catalog: Akt
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 524.8±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 271.2±30.1 °C

UCL-TRO-1938

UCL-TRO-1938 is a potent allosteric activator of PI3Kα with an EC50 value of approximately 60 μM. UCL-TRO-1938 can induce cell proliferation and has cardioprotective and neural regeneration effects[1].

  • CAS Number: 2919575-27-0
  • MF: C27H32N6O
  • MW: 456.58
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI3K-IN-31

PI3K-IN-31 (Compound 6b) is a potent PI3K inhibitor with IC50s of 3.7 nM, 74 nM, 14.6 nM, and 9.9 nM for PI3Kα, PI3Kβ, PI3Kγ, and PI3Kδ, respectively. PI3K-IN-31 has anticancer effects[1].

  • CAS Number: 1359956-12-9
  • MF: C19H23F2N7O3
  • MW: 435.43
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

OSI-027

OSI-027 is an ATP-competitive mTOR kinase activity inhibitor with an IC50 of 4 nM. OSI-027 targets both mTORC1 and mTORC2 with IC50s of 22 nM and 65 nM, respectively.

  • CAS Number: 936890-98-1
  • MF: C21H22N6O3
  • MW: 406.438
  • Catalog: Autophagy
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 591.4±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 311.5±32.9 °C

RLY-2608

RLY-2608 is a first-in-class allosteric mutant-selective inhibitor of PI3Ka[1].

  • CAS Number: 2733573-94-7
  • MF: C29H14ClF5N6O2
  • MW: 608.91
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ATR-IN-24

ATR-IN-24 (Compound 1) is a ATR inhibitor. ATR-IN-24 has anticancer activity[1].

  • CAS Number: 2370889-43-1
  • MF: C23H26N6O2
  • MW: 418.49
  • Catalog: ATM/ATR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BGT226 free base

BGT226 (NVP-BGT226) is a PI3K (with IC50s of 4 nM, 63 nM and 38 nM for PI3Kα, PI3Kβ and PI3Kγ)/mTOR dual inhibitor which displays potent growth-inhibitory activity against human head and neck cancer cells[1][2].

  • CAS Number: 915020-55-2
  • MF: C28H25F3N6O2
  • MW: 534.53
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 713.3±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 385.2±35.7 °C

Bikinin

Bikinin is a non-steroidal, ATP-competitive inhibitor of plant GSK-3/Shaggy-like kinases and activates BR (brassinosteroids) signaling.

  • CAS Number: 188011-69-0
  • MF: C9H9BrN2O3
  • MW: 273.083
  • Catalog: GSK-3
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 521.6±45.0 °C at 760 mmHg
  • Melting Point: 144°C(lit.)
  • Flash Point: 269.2±28.7 °C

2B-(SP) (TFA)

2B-(SP) is a eIF2B-based substrate for glycogen synthase kinase-3 (GSK-3). 2B-(SP) is readily phosphorylated by both the α and β isoforms of GSK-3[1].

  • CAS Number: 186901-17-7
  • MF: C71H123N26O29P
  • MW: 1835.87000
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Manzamine A hydrochloride

Manzamine A hydrochloride, an orally active beta-carboline alkaloid, inhibits specifically GSK-3β and CDK-5 with IC50s of 10.2 and 1.5μM, respectively. Manzamine A hydrochloride targets vacuolar ATPases and inhibits autophagy in pancreatic cancer cells. Manzamine A hydrochloride has antimalarial and anticancer activities. Manzamine A hydrochloride also shows potent activity against HSV-1[1][2][3][4].

  • CAS Number: 104264-80-4
  • MF: C36H45ClN4O
  • MW: 585.22
  • Catalog: HIV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

YM201636

YM-201636 is a potent and selective PIKfyve inhibitor with an IC50 of 33 nM. YM-201636 also inhibits p110α with IC50 of 3.3 μM.

  • CAS Number: 371942-69-7
  • MF: C25H21N7O3
  • MW: 467.479
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

OTSSP167

OTSSP167 is a highly potent MELK inhibitor with IC50 value of 0.41 nM.

  • CAS Number: 1431697-89-0
  • MF: C25H28Cl2N4O2
  • MW: 487.421
  • Catalog: MELK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 619.0±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 328.2±31.5 °C

PI3K-IN-46

PI3K-IN-46 (Intermediate 4) is an intermediate in the synthesis of PI3K inhibitor (2-imino-azolinone-vinyl fused-benzene derivative) that can be used for the research of autoimmune disorders, cardiovascular diseases, and neurodegenerative diseases[1].

  • CAS Number: 304645-61-2
  • MF: C13H9N3OS
  • MW: 255.30
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

VP3.15 dihydrobromide

VP3.15 dihydrobromide is a potent, orally bioavailable and CNS-penetrant dual phosphodiesterase (PDE)7- glycogen synthase kinase (GSK)3 inhibitor, with IC50s of 1.59 μM and 0.88 μM for PDE7 and GSK-3, respectively. VP3.15 dihydrobromide has neuroprotective and neuroreparative activities, thus as potential combined anti-inflammatory and pro-remyelinating therapies for multiple sclerosis (MS)[1].

  • CAS Number: 1281681-33-1
  • MF: C20H24Br2N4OS
  • MW: 528.30
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Gomisin J

Gomisin J is a small molecular weight lignan found in Schisandra chinensis and has been demonstrated to have vasodilatory activity[1]. Gomisin J suppresses lipid accumulation by regulating the expression of lipogenic and lipolytic enzymes and inflammatory molecules through activation of AMPK, LKB1 and Ca2+/calmodulin-dependent protein kinase II and inhibition of fetuin-A in HepG2 cells. gomisin J has potential benefits in treating nonalcoholic fatty liver disease[2].

  • CAS Number: 66280-25-9
  • MF: C22H28O6
  • MW: 388.454
  • Catalog: AMPK
  • Density: 1.161
  • Boiling Point: 587.5±50.0 °C at 760 mmHg
  • Melting Point: 148-149 ºC
  • Flash Point: 309.1±30.1 °C

AZ2

AZ2 is a highly selective PI3Kγ inhibitor (The pIC50 value for PI3Kγ is 9.3). AZ2 can be used for the research of inflammatory and immune diseases[1].

  • CAS Number: 2231760-33-9
  • MF: C20H23N3O2S
  • MW: 369.48
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ATR-IN-16

ATR-IN-16 (compound 46) is a potent ATR kinase inhibitor. ATR-IN-16 shows good anticancer activity in LoVo cells, with an IC50 of 410 nM[1].

  • CAS Number: 2756589-62-3
  • MF: C19H25N7O
  • MW: 367.45
  • Catalog: ATM/ATR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TMBIM6 antagonist-1

TMBIM6 antagonist-1, a potential TMBIM6 antagonist, prevents TMBIM6 binding to mTORC2, decreases mTORC2 activity, and also regulates TMBIM6-leaky Ca2+[1].

  • CAS Number: 123134-61-2
  • MF: C15H12N2O3
  • MW: 268.267383575439
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AMPK activator 11

AMPK activator 11 is an AMP-activated protein kinase (AMPK) activator with nanomolelevel antiproliferation activities against several CRCs. AMPK activator 11 selectively inhibits the RKO xenograft growth along by activating AMPK and upregulating oxidative phosphorylation (OXPHOS) ( mitochondrial metabolism ) and can be used for anti-tumor and metabolic disease research[1].

  • CAS Number: 2948304-00-3
  • MF: C25H20N4O2
  • MW: 408.45
  • Catalog: AMPK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AZD-0156

AZD0156 is an oral, potent and selective ATM inhibitor with an IC50 of 0.58 nM.

  • CAS Number: 1821428-35-6
  • MF: C26H31N5O3
  • MW: 461.556
  • Catalog: ATM/ATR
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 628.3±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 333.8±31.5 °C

HL-8

HL-8 is a PROTAC molecule targeting PI3K kinase. HL-8 has a significant and complete degradation effect on PI3K kinase at a concentration of 10 μM within 8 h. HL-8 has the potential for the research of cancer diseases[1].

  • CAS Number: 2766352-64-9
  • MF: C57H59F2N11O9S2
  • MW: 1144.27
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CAY10404

CAY10404 is a potent and highly selective cyclooxygenase-2 (COX-2) inhibitor with an IC50 of 1 nM. CAY10404 exhibits no inhibition of COX-1 (IC50>500 µM)[1]. CAY10404 is a potent inhibitor of PKB/Akt and MAPK signaling pathways and induces apoptosis in NSCLC cells. CAY10404, a diarylisoxazole, has good analgesic, anti-inflammatory, and anti-cancer activities[2][3].

  • CAS Number: 340267-36-9
  • MF: C17H12F3NO3S
  • MW: 367.342
  • Catalog: Apoptosis
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 498.6±45.0 °C at 760 mmHg
  • Melting Point: 196.47 °C(Predicted)
  • Flash Point: 255.3±28.7 °C

CHMFL-PI3KD-317

CHMFL-PI3KD-317 is a highly potent, selective and orally active PI3Kδ inhibitor, with an IC50s of 6 nM, and exhibits over 10-1500 fold selectivity over other class I, II and III PIKK family isoforms, such as PI3Kα (IC50, 62.6 nM), PI3Kβ (IC50, 284 nM), PI3Kγ (IC50, 202.7 nM), PIK3C2A (IC50, >10000 nM), PIK3C2B (IC50, 882.3 nM), VPS34 (IC50, 1801.7 nM), PI4KIIIA (IC50, 574.1 nM) and PI4KIIIB (IC50, 300.2 nM). CHMFL-PI3KD-317 inhibits PI3Kδ-mediated Akt T308 phosphorylation in Raji cells, with an EC50 of 4.3 nM. CHMFL-PI3KD-317 has antiproliferative effects on cancer cells[1].

  • CAS Number: 2244992-76-3
  • MF: C21H24ClN5O3S2
  • MW: 494.03
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI3K/mTOR Inhibitor-8

PI3K/mTOR Inhibitor-8 (Compound 18b) is a PI3K and mTOR dual inhibitor with IC50 values of 0.46 nM and 12 nM against PI3Kα and mTOR, respectively. PI3K/mTOR Inhibitor-8 induces HCT-116 cells apoptosis and arrests cell cycle at the G1/S phase[1].

  • CAS Number: 2492376-85-7
  • MF: C23H22N8O4S
  • MW: 506.54
  • Catalog: mTOR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI3Kδ-IN-16

PI3Kδ-IN-16 is a potent and selective inhibitor of PI3Kδ. PI3Kδ-IN-16 has a strong anti-proliferative effect on cells, causing cell cycle arrest and inducing apoptosis[1].

  • CAS Number: 2766437-35-6
  • MF: C22H26N6O2
  • MW: 406.48
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NVS-PI3-4

NVS-PI3-4 is a specific PI3Kγ inhibitor. NVS-PI3-4 can be used for the research of allergies, inflammatory and cancer diseases[1][2].

  • CAS Number: 941580-60-5
  • MF: C20H26N4O3S
  • MW: 402.51
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PI4KIIIbeta-IN-11

PI4KIIIbeta-IN-11 is an inhibitor of PI4KIIIβ, with a mean pIC50 value of at least 9.1. PI4KIIIβ plays a key role in diseases research of RNA viruses and Plasmodium falciparum[1][2].

  • CAS Number: 2365241-79-6
  • MF: C33H39N7O3
  • MW: 581.71
  • Catalog: PI4K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MMP-9-IN-3

MMP-9-IN-3 is a MMP-9 inhibitor (IC50: 5.56 nM) that forms hydrogen bond with MMP-9. MMP-9-IN-3 also inhibits AKT activity (IC50: 2.11 nM). MMP-9-IN-3 shows cell cytotoxicity and induces cell apoptosis. MMP-9-IN-3 can be used in the research of cancers[1].

  • CAS Number: 2581824-48-6
  • MF: C29H25N3O4
  • MW: 479.53
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KU55933 (ATM Kinase Inhibitor)

KU-55933 is a potent ATM inhibitor with an IC50 and Ki of 12.9 and 2.2 nM, respectively, and is highly selective for ATM as compared to DNA-PK, PI3K/PI4K, ATR and mTOR.

  • CAS Number: 587871-26-9
  • MF: C21H17NO3S2
  • MW: 395.495
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 628.0±55.0 °C at 760 mmHg
  • Melting Point: 229.98° C
  • Flash Point: 333.6±31.5 °C

Akt-l-1

AKT-I-1 is a selective inhibitor of Akt1, with an IC50 of 4.6 µM[1].

  • CAS Number: 473382-39-7
  • MF: C22H30N6
  • MW: 378.514
  • Catalog: Akt
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A