PMID- 21591993
OWN - NLM
STAT- MEDLINE
DCOM- 20111013
LR  - 20211203
IS  - 1744-7674 (Electronic)
IS  - 1354-3776 (Linking)
VI  - 21
IP  - 7
DP  - 2011 Jul
TI  - Recent advances in the discovery of small-molecule ATP competitive mTOR 
      inhibitors: a patent review.
PG  - 1109-27
LID - 10.1517/13543776.2011.584871 [doi]
AB  - INTRODUCTION: The mammalian target of rapamycin (mTOR) is a protein kinase and a 
      key component of the PI3K/Akt/mTOR signaling pathway, and is deregulated in half 
      of all human cancers. Rapamycin and its analogs (rapalogs) are allosteric 
      inhibitors of one functional mTOR complex, mTORC1, and are clinically proven 
      therapeutic agents for the treatment of certain cancers. However, rapalogs mainly 
      partially inhibit mTORC1, while ATP competitive inhibitors suppress both mTORC1 
      and mTORC2, and therefore may offer advantages in the clinic. Recently, 
      small-molecule inhibitors have entered clinical trials that are mTOR-selective or 
      dual mTOR/PI3K inhibitors. AREAS COVERED: This review focuses on ATP-competitive 
      mTOR inhibitors that have appeared in the patent literature in 2010. Many 
      inhibitors with new structural motifs have been discovered as well as inhibitors 
      that are related to previously disclosed structures. This review endeavors to put 
      into perspective the diverse structural elements that make up these compounds. 
      Patent applications are covered that include either selective mTOR inhibitors or 
      dual mTOR/PI3K inhibitors. EXPERT OPINION: The PI3K/mTOR signaling pathway is an 
      exciting target for the development of pharmaceuticals to treat cancer and other 
      diseases, due to the unique combination of a clinically and commercially 
      validated pathway approach (i.e., rapalogs), combined with a biological rationale 
      for further increased efficacy (i.e., ATP-competitive inhibitors). With the 
      number of candidate drugs currently in development or at earlier stages of the 
      drug discovery pipeline, we are bound to see small-molecule inhibitors reach 
      pivotal trials, and hopefully the market, in the near future.
FAU - Zask, Arie
AU  - Zask A
AD  - Columbia University, Department of Chemistry, 3000 Broadway, NY, NY 10027, USA. 
      ariez@aol.com
FAU - Verheijen, Jeroen C
AU  - Verheijen JC
FAU - Richard, David J
AU  - Richard DJ
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20110519
PL  - England
TA  - Expert Opin Ther Pat
JT  - Expert opinion on therapeutic patents
JID - 9516419
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adenosine Triphosphate/*metabolism
MH  - Animals
MH  - Antineoplastic Agents/pharmacology
MH  - Binding, Competitive
MH  - Drug Delivery Systems
MH  - Drug Design
MH  - Humans
MH  - Neoplasms/drug therapy/physiopathology
MH  - Patents as Topic
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
EDAT- 2011/05/20 06:00
MHDA- 2011/10/14 06:00
CRDT- 2011/05/20 06:00
PHST- 2011/05/20 06:00 [entrez]
PHST- 2011/05/20 06:00 [pubmed]
PHST- 2011/10/14 06:00 [medline]
AID - 10.1517/13543776.2011.584871 [doi]
PST - ppublish
SO  - Expert Opin Ther Pat. 2011 Jul;21(7):1109-27. doi: 10.1517/13543776.2011.584871. 
      Epub 2011 May 19.