WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 202094
CAS#: 936890-98-1 (free acid)
Description: OSI-027 is an orally bioavailable mammalian target of rapamycin (mTOR) kinase inhibitor with potential antineoplastic activity. mTOR kinase inhibitor OSI-027 binds to and inhibits both the raptor-mTOR (TOR complex 1 or TORC1) and the rictor-mTOR (TOR complex 2 or TORC2) complexes of mTOR, which may result in tumor cell apoptosis and a decrease in tumor cell proliferation. mTOR is a serine/threonine kinase that is upregulated in some tumors and plays an important role downstream in the PI3K/Akt/mTOR signaling pathway. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).
MedKoo Cat#: 202094
CAS#: 936890-98-1 (free acid)
Chemical Formula: C21H22N6O3
Exact Mass: 406.1753
Molecular Weight: 406.45
Elemental Analysis: C, 62.06; H, 5.46; N, 20.68; O, 11.81
Related CAS #: 1187559-64-3 (calcium) 1187559-66-5 (sodium) 1187559-73-4 (potassium) 936890-98-1 (free acid)
Synonym: OSI027; OSI-027; OSI 027.
IUPAC/Chemical Name: trans-4-[4-amino-5-(7-methoxy-1H-indol-2-yl)imidazo[5,1-f][1,2,4]triazin-7-yl]-cyclohexanecarboxylic acid
InChi Key: JROFGZPOBKIAEW-HAQNSBGRSA-N
InChi Code: 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-
SMILES Code: O=C([C@H]1CC[C@H](C2=NC(C(N3)=CC4=C3C(OC)=CC=C4)=C5C(N)=NC=NN52)CC1)O
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not soluble in water.
Shelf Life: >5 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
The following data is based on the product molecular weight 406.45 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
1: Chen BW, Chen W, Liang H, Liu H, Liang C, Zhi X, Hu LQ, Yu XZ, Wei T, Ma T, Xue F, Zheng L, Zhao B, Feng XH, Bai XL, Liang TB. Inhibition of mTORC2 induces cell cycle arrest and enhances the cytotoxicity of doxorubicin by suppressing MDR1 expression in HCC cells. Mol Cancer Ther. 2015 May 29. pii: molcanther.0029.2015. [Epub ahead of print] PubMed PMID: 26026051.
2: Colamonici M, Blyth G, Saleiro D, Szilard A, Bliss-Moreau M, Giles FJ, Altman JK, Beauchamp EM, Platanias LC. Dual targeting of acute myeloid leukemia progenitors by catalytic mTOR inhibition and blockade of the p110α subunit of PI3 kinase. Oncotarget. 2015 Apr 10;6(10):8062-70. PubMed PMID: 25823922; PubMed Central PMCID: PMC4480735.
3: Williams R. Discontinued in 2013: oncology drugs. Expert Opin Investig Drugs. 2015 Jan;24(1):95-110. Epub 2014 Oct 14. PubMed PMID: 25315907.
4: Becker MN, Wu KJ, Marlow LA, Kreinest PA, Vonroemeling CA, Copland JA, Williams CR. The combination of an mTORc1/TORc2 inhibitor with lapatinib is synergistic in bladder cancer in vitro. Urol Oncol. 2014 Apr;32(3):317-26. doi: 10.1016/j.urolonc.2013.06.002. Epub 2013 Sep 17. PubMed PMID: 24054871.
5: Cassell A, Freilino ML, Lee J, Barr S, Wang L, Panahandeh MC, Thomas SM, Grandis JR. Targeting TORC1/2 enhances sensitivity to EGFR inhibitors in head and neck cancer preclinical models. Neoplasia. 2012 Nov;14(11):1005-14. PubMed PMID: 23226094; PubMed Central PMCID: PMC3514742.
6: Li H, Lin J, Wang X, Yao G, Wang L, Zheng H, Yang C, Jia C, Liu A, Bai X. Targeting of mTORC2 prevents cell migration and promotes apoptosis in breast cancer. Breast Cancer Res Treat. 2012 Aug;134(3):1057-66. doi: 10.1007/s10549-012-2036-2. Epub 2012 Apr 4. PubMed PMID: 22476852.
7: Gupta M, Hendrickson AE, Yun SS, Han JJ, Schneider PA, Koh BD, Stenson MJ, Wellik LE, Shing JC, Peterson KL, Flatten KS, Hess AD, Smith BD, Karp JE, Barr S, Witzig TE, Kaufmann SH. Dual mTORC1/mTORC2 inhibition diminishes Akt activation and induces Puma-dependent apoptosis in lymphoid malignancies. Blood. 2012 Jan 12;119(2):476-87. doi: 10.1182/blood-2011-04-346601. Epub 2011 Nov 11. PubMed PMID: 22080480; PubMed Central PMCID: PMC3257013.
8: Bhagwat SV, Gokhale PC, Crew AP, Cooke A, Yao Y, Mantis C, Kahler J, Workman J, Bittner M, Dudkin L, Epstein DM, Gibson NW, Wild R, Arnold LD, Houghton PJ, Pachter JA. Preclinical characterization of OSI-027, a potent and selective inhibitor of mTORC1 and mTORC2: distinct from rapamycin. Mol Cancer Ther. 2011 Aug;10(8):1394-406. doi: 10.1158/1535-7163.MCT-10-1099. Epub 2011 Jun 14. PubMed PMID: 21673091.
9: Schenone S, Brullo C, Musumeci F, Radi M, Botta M. ATP-competitive inhibitors of mTOR: an update. Curr Med Chem. 2011;18(20):2995-3014. Review. PubMed PMID: 21651476.
10: Altman JK, Sassano A, Kaur S, Glaser H, Kroczynska B, Redig AJ, Russo S, Barr S, Platanias LC. Dual mTORC2/mTORC1 targeting results in potent suppressive effects on acute myeloid leukemia (AML) progenitors. Clin Cancer Res. 2011 Jul 1;17(13):4378-88. doi: 10.1158/1078-0432.CCR-10-2285. Epub 2011 Mar 17. PubMed PMID: 21415215; PubMed Central PMCID: PMC3131493.
Phase I trial results: To date, 34 pts have been enrolled (13M/21F, median age 59 yrs) and 31 treated (S1 11 pts, S2 12 pts, S3 8 pts). S1 and S2 pts were dosed at 10, 15 and 20 mg, S3 pts at 5, 10 and 20 mg. Median number of weeks on study was 6 (range <1-34). Three DLTs have been reported: grade (G) 2 decreased LVEF (10mg S1), and 2 pts with G3 fatigue (15 mg S2 and 20 mg S3). Other drug-related toxicities included G3 nausea and vomiting (1), G3 pneumonia (1); G1/2 fatigue (4), nausea (2), diarrhea (1), anorexia (1), elevated creatinine (1), and reversible increase in QTc (1). Preliminary PK indicate exposure (AUC, Cmax) of OSI-027 increased with dose. The median Tmax and terminal T3/4 were 2-6 hrs and 6-17 hrs, respectively. Preliminary PD data indicate that substantial decreases in 4E-BP1 (T37/46) phosphorylation were observed in PBMCs from 13 of 23 pts following OSI-027 treatment. Eight pts have had SD lasting ≥ 12 wks (26% of pts treated, range 12-33 wks); tumor types were colorectal (3 pts), melanoma, neuroendocrine, endometrial, renal, and cervical cancer (1 pt each). Conclusions: OSI-027 is a potent TORC1/2 kinase inhibitor. Preliminary evidence of pharmacological activity has been observed. It is well tolerated at the doses and schedules tested to date. MTD has not been reached and dose escalation is ongoing. (source: Journal of Clinical Oncology, 2010 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 28, No 15_suppl (May 20 Supplement), 2010: 3006. or http://meeting.ascopubs.org/cgi/content/abstract/28/15_suppl/3006).