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PDBsum entry 6f23
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References listed in PDB file
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Key reference
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Title
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Creation of a novel class of potent and selective mutt homologue 1 (mth1) inhibitors using fragment-Based screening and structure-Based drug design.
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Authors
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F.Rahm,
J.Viklund,
L.Trésaugues,
M.Ellermann,
A.Giese,
U.Ericsson,
R.Forsblom,
T.Ginman,
J.Günther,
K.Hallberg,
J.Lindström,
L.B.Persson,
C.Silvander,
A.Talagas,
L.Díaz-Sáez,
O.Fedorov,
K.V.M.Huber,
I.Panagakou,
P.Siejka,
M.Gorjánácz,
M.Bauser,
M.Andersson.
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Ref.
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J Med Chem, 2018,
61,
2533-2551.
[DOI no: ]
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PubMed id
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Abstract
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Recent literature has both suggested and questioned MTH1 as a novel cancer
target. BAY-707 was just published as a target validation small molecule probe
for assessing the effects of pharmacological inhibition of MTH1 on tumor cell
survival, both in vitro and in vivo. (1) In this report, we describe the
medicinal chemistry program creating BAY-707, where fragment-based methods were
used to develop a series of highly potent and selective MTH1 inhibitors. Using
structure-based drug design and rational medicinal chemistry approaches, the
potency was increased over 10,000 times from the fragment starting point while
maintaining high ligand efficiency and drug-like properties.
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