PP242 --- mTORC1/mTORC2 inhibitor

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.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

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:

1. Feldman ME, et al. Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2. (2009) PLoS Biol. 7(2):e38.
2. Janes MR, et al. Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor.(2010) Nat Med. 16(2):205-13.
3. Hoang B, et al. Targeting TORC2 in multiple myeloma with a new mTOR kinase inhibitor. (2010) Blood. 116(22):4560-8.
4. 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.

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