Product Name :
PP242 — mTORC1/mTORC2 inhibitor
Description:
PP242 is a highly potent, selective and ATP-competitive mTORC1/mTORC2 inhibitor (IC50 = 8 nM). It has > 10 folds selectivity over the other PI-3K family kinases (IC50 0.102 µM, 0.408 µM, 1.27 µM, 1.96 µM and 2.2 μM for p110γ, DNA-PK, p110δ, p110α and p110β, respectively). Except some weak inhibitory activity against PKCα, JAK2, PKCβI, PKCβII and RET (0.05-0.22 µM), PP242 exhibits excellent selectivity over 215 other protein kinases. PP242 differentially inhibits insulin-stimulated phosphorylations of cellular proteins both in vitro and in vivo in a manner distinctly different from that seen in mTORC2-functional knockout SIN1-/- cells or in cultures treated with Rapamycin, which targets only mTORC1, but not mTORC2. Blockage of 4EBP1 T36/T45/S65 phosphorylation by PP242 upon insulin stimulation in primary MEFs correlates well with an enhanced 4EBP1 association with the cap-binding protein eIF4E, resulting in a selective inhibition of cap-dependent, but not cap-independent, protein translation.
CAS:
1092351-67-1
Molecular Weight:
308.34
Formula:
C16H16N6O
Chemical Name:
2-(4-amino-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol
Smiles :
CC(C)N1N=C(C2=C(N)N=CN=C12)C1=CC2=CC(O)=CC=C2N1
InChiKey:
MFAQYJIYDMLAIM-UHFFFAOYSA-N
InChi :
InChI=1S/C16H16N6O/c1-8(2)22-16-13(15(17)18-7-19-16)14(21-22)12-6-9-5-10(23)3-4-11(9)20-12/h3-8,20,23H,1-2H3,(H2,17,18,19)
Purity:
≥98% (or refer to the Certificate of Analysis)
Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis
Storage Condition :
Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.
Shelf Life:
≥12 months if stored properly.
Stock Solution Storage:
0 – 4 oC for 1 month or refer to the Certificate of Analysis.
Additional information:
PP242 is a highly potent, selective and ATP-competitive mTORC1/mTORC2 inhibitor (IC50 = 8 nM). It has > 10 folds selectivity over the other PI-3K family kinases (IC50 0.102 µM, 0.408 µM, 1.27 µM, 1.96 µM and 2.2 μM for p110γ, DNA-PK, p110δ, p110α and p110β, respectively). Except some weak inhibitory activity against PKCα, JAK2, PKCβI, PKCβII and RET (0.05-0.22 µM), PP242 exhibits excellent selectivity over 215 other protein kinases. PP242 differentially inhibits insulin-stimulated phosphorylations of cellular proteins both in vitro and in vivo in a manner distinctly different from that seen in mTORC2-functional knockout SIN1-/- cells or in cultures treated with Rapamycin, which targets only mTORC1, but not mTORC2. Blockage of 4EBP1 T36/T45/S65 phosphorylation by PP242 upon insulin stimulation in primary MEFs correlates well with an enhanced 4EBP1 association with the cap-binding protein eIF4E, resulting in a selective inhibition of cap-dependent, but not cap-independent, protein translation.|Product information|CAS Number: 1092351-67-1|Molecular Weight: 308.34|Formula: C16H16N6O|Synonym:|Torkinib|Chemical Name: 2-(4-amino-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol|Smiles: CC(C)N1N=C(C2=C(N)N=CN=C12)C1=CC2=CC(O)=CC=C2N1|InChiKey: MFAQYJIYDMLAIM-UHFFFAOYSA-N|InChi: InChI=1S/C16H16N6O/c1-8(2)22-16-13(15(17)18-7-19-16)14(21-22)12-6-9-5-10(23)3-4-11(9)20-12/h3-8,20,23H,1-2H3,(H2,17,18,19)|Technical Data|Appearance: Solid Power.|Purity: ≥98% (or refer to the Certificate of Analysis)|Solubility: DMSO up to 100 mM|Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis|Storage Condition: Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.{{Protein A/G Agarose} medchemexpress|{Protein A/G Agarose} NF-κB|{Protein A/G Agarose} Technical Information|{Protein A/G Agarose} Purity|{Protein A/G Agarose} custom synthesis} |Shelf Life: ≥12 months if stored properly.{{α-Linolenic acid} MedChemExpress|{α-Linolenic acid} PI3K|{α-Linolenic acid} Biological Activity|{α-Linolenic acid} Purity|{α-Linolenic acid} custom synthesis|{α-Linolenic acid} Cancer} |Stock Solution Storage: 0 – 4 oC for 1 month or refer to the Certificate of Analysis.PMID:23962101 |Drug Formulation: To be determined.|HS Tariff Code: 382200|How to use|In Vitro:|PP242 was used at 2.5 µM concentration in vitro and in cellular assays.|In Vivo:|PP242 was orally dosed to mice at 20-60 mg/kg once per day to inhibit tumor growth, or in combination with Dasatinib, Bortezomib or Imatinib for synergistic activity.|References:|Feldman ME, et al. Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2. (2009) PLoS Biol. 7(2):e38.Janes MR, et al. Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor.(2010) Nat Med. 16(2):205-13.Hoang B, et al. Targeting TORC2 in multiple myeloma with a new mTOR kinase inhibitor. (2010) Blood. 116(22):4560-8.Liu Q, et al. Kinome-wide selectivity profiling of ATP-competitive mammalian target of rapamycin (mTOR) inhibitors and characterization of their binding kinetics. (2012) J Biol Chem. 287(13):9742-52.Products are for research use only. Not for human use.|Documents||
