OSI-027 --- mTOR Inhibitor

OSI-027 is a selective and potent dual inhibitor of mTORC1 and mTORC2 with IC50 of 22 nM and 65 nM, respectively. It shows more than 100-fold selectivity for mTOR relative to PI3Kα, PI3Kβ, PI3Kγ, and DNA-PK. It inhibits phosphorylation of the mTORC1 substrates 4E-BP1 and S6K1 as well as the mTORC2 substrate AKT in diverse cancer models in vitro and in vivo. OSI-027 shows robust antitumor activity in several different human xenograft models representing various histologies. In COLO 205 and GEO colon cancer xenograft models, OSI-027 showed superior efficacy compared with rapamycin. OSI-027 is currently in Phase I clinical trials in patients with advanced solid tumors or lymphoma.

Product information

CAS Number: 936890-98-1

Molecular Weight: 406.44

Formula: C21H22N6O3

Chemical Name: (1r,4r)-4-(4-amino-5-(7-methoxy-1H-indol-2-yl)imidazo[5,1-f][1,2,4]triazin-7-yl)cyclohexanecarboxylic acid

Smiles: COC1=CC=CC2C=C(NC=21)C1N=C([C@@H]2CC[C@H](CC2)C(O)=O)N2N=CN=C(N)C2=1

InChiKey: JROFGZPOBKIAEW-HAQNSBGRSA-N

InChi: InChI=1S/C21H22N6O3/c1-30-15-4-2-3-13-9-14(25-16(13)15)17-18-19(22)23-10-24-27(18)20(26-17)11-5-7-12(8-6-11)21(28)29/h2-4,9-12,25H,5-8H2,1H3,(H,28,29)(H2,22,23,24)/t11-,12-

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO up to 50 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:

OSI-027 was used at 1-10 µM in vitro and in cellular assays.

In Vivo:

OSI-027 was orally dosed to mice at 50-65 mg/kg once per day.

References:

1. Vakana E, et al. Induction of autophagy by dual mTORC1-mTORC2 inhibition in BCR-ABL-expressing leukemic cells. (2010) Autophagy. 6(7):966-7.
2. Carayol N,et al. Critical roles for mTORC2- and rapamycin-insensitive mTORC1-complexes in growth and survival of BCR-ABL-expressing leukemic cells. (2010) Proc Natl Acad Sci USA. 107(28):12469-74.
3. Falcon BL, et al. Reduced VEGF production, angiogenesis, and vascular regrowth contribute to the antitumor properties of dual mTORC1/mTORC2 inhibitors. (2011) Cancer Res. 71(5):1573-83.

Products are for research use only. Not for human use.

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