PMID- 15848770
OWN - NLM
STAT- MEDLINE
DCOM- 20050908
LR  - 20121115
IS  - 0968-0896 (Print)
IS  - 0968-0896 (Linking)
VI  - 13
IP  - 10
DP  - 2005 May 16
TI  - Design, synthesis, and biological evaluation of 10-methanesulfonyl-DDACTHF, 
      10-methanesulfonyl-5-DACTHF, and 10-methylthio-DDACTHF as potent inhibitors of 
      GAR Tfase and the de novo purine biosynthetic pathway.
PG  - 3577-85
AB  - The synthesis and evaluation of 10-methanesulfonyl-DDACTHF (1), 
      10-methanesulfonyl-5-DACTHF (2), and 10-methylthio-DDACTHF (3) as potential 
      inhibitors of glycinamide ribonucleotide transformylase (GAR Tfase) and 
      aminoimidazole carboxamide ribonucleotide transformylase (AICAR Tfase) are 
      reported. The compounds 10-methanesulfonyl-DDACTHF (1, K(i) = 0.23 microM), 
      10-methanesulfonyl-5-DACTHF (2, K(i) = 0.58 microM), and 10-methylthio-DDACTHF 
      (3, K(i) = 0.25 microM) were found to be selective and potent inhibitors of 
      recombinant human GAR Tfase. Of these, 3 exhibited exceptionally potent, purine 
      sensitive growth inhibition activity (3, IC50 = 100 nM) against the CCRF-CEM cell 
      line being 3-fold more potent than Lometrexol and 30-fold more potent than the 
      parent, unsubstituted DDACTHF, whereas 1 and 2 exhibited more modest growth 
      inhibition activity (1, IC50 = 1.0 microM and 2, IC50 = 2.0 microM).
FAU - Cheng, Heng
AU  - Cheng H
AD  - Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines 
      Road, La Jolla, CA 92037, USA.
FAU - Chong, Youhoon
AU  - Chong Y
FAU - Hwang, Inkyu
AU  - Hwang I
FAU - Tavassoli, Ali
AU  - Tavassoli A
FAU - Zhang, Yan
AU  - Zhang Y
FAU - Wilson, Ian A
AU  - Wilson IA
FAU - Benkovic, Stephen J
AU  - Benkovic SJ
FAU - Boger, Dale L
AU  - Boger DL
LA  - eng
GR  - CA 63536/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Bioorg Med Chem
JT  - Bioorganic & medicinal chemistry
JID - 9413298
RN  - 0 (10-methanesulfonyl-5-DACTHF)
RN  - 0 (10-methanesulfonyl-DDACTHF)
RN  - 0 (10-methylthio-DDACTHF)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Purines)
RN  - 0 (Tetrahydrofolates)
RN  - 6P3AVY8A7Q (lometrexol)
RN  - EC 2.1.2.- (Hydroxymethyl and Formyl Transferases)
RN  - EC 2.1.2.2 (Phosphoribosylglycinamide Formyltransferase)
RN  - EC 2.1.2.3 (Phosphoribosylaminoimidazolecarboxamide Formyltransferase)
SB  - IM
MH  - Antineoplastic Agents/*chemical synthesis/*pharmacology
MH  - Cell Survival/drug effects
MH  - *Drug Design
MH  - Enzyme Inhibitors/chemical synthesis/chemistry/pharmacology
MH  - Evaluation Studies as Topic
MH  - Humans
MH  - Hydroxymethyl and Formyl Transferases/*antagonists & inhibitors
MH  - Inhibitory Concentration 50
MH  - Phosphoribosylaminoimidazolecarboxamide Formyltransferase
MH  - Phosphoribosylglycinamide Formyltransferase
MH  - Purines/antagonists & inhibitors/metabolism
MH  - Structure-Activity Relationship
MH  - Tetrahydrofolates/*chemical synthesis/chemistry/*pharmacology
MH  - Tumor Cells, Cultured
EDAT- 2005/04/26 09:00
MHDA- 2005/09/09 09:00
CRDT- 2005/04/26 09:00
PHST- 2004/09/30 00:00 [received]
PHST- 2004/12/02 00:00 [revised]
PHST- 2004/12/02 00:00 [accepted]
PHST- 2005/04/26 09:00 [pubmed]
PHST- 2005/09/09 09:00 [medline]
PHST- 2005/04/26 09:00 [entrez]
AID - S0968-0896(04)00964-2 [pii]
AID - 10.1016/j.bmc.2004.12.004 [doi]
PST - ppublish
SO  - Bioorg Med Chem. 2005 May 16;13(10):3577-85. doi: 10.1016/j.bmc.2004.12.004.