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About Claire Sadler

Dr Claire Sadler PhD. Claire is an experienced project toxicologist and former Director of Discovery Safety within AstraZeneca. Claire specialises in early project safety assessment, identifying and mitigating risks from target identification through to early clinical trials. She has worked across multiple therapy areas including oncology, infection, immune and cardiovascular, and on many drug platforms including small molecules, proteins and novel platforms. She has been directly involved in bringing many candidate drugs to clinical trial, submitted through different territory regulatory agencies. She has a proven track record in problem solving and in investigational cellular and molecular toxicology. She is expert in designing and implementing bespoke safety packages and in developing strategies to drive compound design and selection.

Towards better models and mechanistic biomarkers for drug-induced gastrointestinal injury.

Abstract Adverse drug reactions affecting the gastrointestinal (GI) tract are a serious burden on patients, healthcare providers and the pharmaceutical industry. GI toxicity encompasses a range of pathologies in different parts of the GI tract. However, to date no specific mechanistic diagnostic/prognostic biomarkers or translatable pre-clinical models of GI toxicity exist. This review will cover [...]

By |2018-10-24T16:45:28+01:00April 27th, 2017|Toxicology, Publications|Comments Off on Towards better models and mechanistic biomarkers for drug-induced gastrointestinal injury.

Discovery of benzothiazoles as antimycobacterial agents: Synthesis, structure–activity relationships and binding studies with Mycobacterium tuberculosis decaprenylphosphoryl-β-d-ribose 2′-oxidase

Abstract We report the discovery of benzothiazoles, a novel anti-mycobacterial series, identified from a whole cell based screening campaign. Benzothiazoles exert their bactericidal activity against Mycobacterium tuberculosis (Mtb) through potent inhibition of decaprenylphosphoryl-β-d-ribose 2′-oxidase (DprE1), the key enzyme involved in arabinogalactan synthesis. Specific target linkage and mode of binding were established using co-crystallization and protein mass spectrometry [...]

By |2018-10-24T16:48:44+01:00December 24th, 2015|Toxicology, Publications|Comments Off on Discovery of benzothiazoles as antimycobacterial agents: Synthesis, structure–activity relationships and binding studies with Mycobacterium tuberculosis decaprenylphosphoryl-β-d-ribose 2′-oxidase

Induction of heart valve lesions by small-molecule ALK5 inhibitors.

Abstract Aberrant signaling by transforming growth factor-β (TGF-β) and its type I (ALK5) receptor has been implicated in a number of human diseases and this pathway is considered a potential target for therapeutic intervention. Transforming growth factor-β signaling via ALK5 plays a critical role during heart development, but the role of ALK5 in the adult [...]

By |2018-10-24T16:53:37+01:00August 27th, 2011|Toxicology, Publications|Comments Off on Induction of heart valve lesions by small-molecule ALK5 inhibitors.