5 research outputs found
Creation of a Novel Class of Potent and Selective MutT Homologue 1 (MTH1) Inhibitors Using Fragment-Based Screening and Structure-Based Drug Design
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 <i>in vitro</i> and <i>in vivo.</i> 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
Creation of a Novel Class of Potent and Selective MutT Homologue 1 (MTH1) Inhibitors Using Fragment-Based Screening and Structure-Based Drug Design
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 <i>in vitro</i> and <i>in vivo.</i> 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
Creation of a Novel Class of Potent and Selective MutT Homologue 1 (MTH1) Inhibitors Using Fragment-Based Screening and Structure-Based Drug Design
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 <i>in vitro</i> and <i>in vivo.</i> 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
Creation of a Novel Class of Potent and Selective MutT Homologue 1 (MTH1) Inhibitors Using Fragment-Based Screening and Structure-Based Drug Design
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 <i>in vitro</i> and <i>in vivo.</i> 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
Discovery of a Series of Indole‑2 Carboxamides as Selective Secreted Phospholipase A<sub>2</sub> Type X (sPLA<sub>2</sub>‑X) Inhibitors
In order to assess the potential
of sPLA<sub>2</sub>-X as a therapeutic target for atherosclerosis,
novel sPLA<sub>2</sub> inhibitors with improved type X selectivity
are required. To achieve the objective of identifying such compounds,
we embarked on a lead generation effort that resulted in the identification
of a novel series of indole-2-carboxamides as selective sPLA2-X inhibitors
with excellent potential for further optimization