title: Trypsin inhibitors for the treatment of pancreatitis.
abstract: Proline-based trypsin inhibitors occupying the S1-S2-S1' region were identified by an HTS screening campaign. It was discovered that truncation of the P1' moiety and appropriate extension into the S4 region led to highly potent trypsin inhibitors with excellent selectivity against related serine proteases and a favorable hERG profile.
authors.affiliation: Novartis Pharma AG, Novartis Institutes for BioMedical Research, Novartis Campus, CH-4002 Basel, Switzerland. Electronic address: trixi.brandl@novartis.com.
authors.forename: Trixi
authors.initials: T
authors.lastname: Brandl
authors.affiliation: Novartis Pharma AG, Novartis Institutes for BioMedical Research, Novartis Campus, CH-4002 Basel, Switzerland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Simic
authors.affiliation: Novartis Pharma AG, Novartis Institutes for BioMedical Research, Novartis Campus, CH-4002 Basel, Switzerland.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Skaanderup
authors.affiliation: Novartis Pharma AG, Novartis Institutes for BioMedical Research, Novartis Campus, CH-4002 Basel, Switzerland.
authors.forename: Kenji
authors.initials: K
authors.lastname: Namoto
authors.affiliation: Novartis Pharma AG, Novartis Institutes for BioMedical Research, Novartis Campus, CH-4002 Basel, Switzerland.
authors.forename: Frederic
authors.initials: F
authors.lastname: Berst
authors.affiliation: Novartis Pharma AG, Novartis Institutes for BioMedical Research, Novartis Campus, CH-4002 Basel, Switzerland.
authors.forename: Claus
authors.initials: C
authors.lastname: Ehrhardt
authors.affiliation: Novartis Pharma AG, Novartis Institutes for BioMedical Research, Novartis Campus, CH-4002 Basel, Switzerland.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Schiering
authors.affiliation: Novartis Pharma AG, Novartis Institutes for BioMedical Research, Novartis Campus, CH-4002 Basel, Switzerland.
authors.forename: Irene
authors.initials: I
authors.lastname: Mueller
authors.affiliation: Novartis Pharma AG, Cardio Metabolic Development Franchise, Novartis Campus, CH-4002 Basel, Switzerland.
authors.forename: Julian
authors.initials: J
authors.lastname: Woelcke
mesh_terms: D018360:Crystallography, X-Ray; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010195:Pancreatitis / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D014361:Trypsin Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D014361:Trypsin Inhibitors
keywords: Pancreatitis; Trypsin inhibitor; X-ray crystal structure; hERG inhibition