Cayetana Zárate

Discovery and In Vivo Evaluation of Aryl Ether YAP1/TEAD Inhibitors for the Treatment of Hippo-Driven Malignancies

Brandon Vara, Jongwon Lim, Casey J. Moure, Sebastian E. Schneider et autres

Targeting the YAP1/TEAD interaction, a critical Hippo pathway signaling complex involved in transcriptional aberrations in cancer, represents a novel approach for treating Hippo-driven malignancies including mesothelioma. Our discovery campaign relied on virtual screening, X-ray crystallography and structure–activity relationship (SAR) studies were carried …

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An Expedient Synthetic Route to the Long-Acting RSV Inhibitor JNJ-6231 via Stereoselective Enzymatic Amination and Regioselective Alkylation

Trung D.C. Cao, Katharina Neufeld, Cayetana Zárate, Christopher James Nichols et autres

JNJ-6231 was discovered as a second-generation long-acting RSV inhibitor and served as a follow-up candidate to our previous candidate JNJ-7950. Early development synthetic route investigation identified a diastereomerically pure spiro-cyclobutyl amine, an alkyl chloride containing a benzimidazole, and a chiral difluoromethyl-containing carboxylic …

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Discovery and Optimization of N-Heteroaryl Indazole LRRK2 Inhibitors

Kaitlyn M. Logan, Will Kaplan, Vladimir Simov, Hua Zhou et autres

Inhibition of leucine-rich repeat kinase 2 is a genetically supported mechanism for the treatment of Parkinson’s disease. We previously disclosed the discovery of an indazole series lead that demonstrated both safety and translational risks. The safety risks were hypothesized to be of …

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Academic-Industrial Collaborations: Merging Paths to Thrive

Hongli Bao, Karla Bravo‐Altamirano, Zachary A. Buchan, Pablo J. Cabrera et autres

ADVERTISEMENT RETURN TO ISSUEEditorialNEXTAcademic-Industrial Collaborations: Merging Paths to ThriveHongli BaoHongli BaoKey Laboratory of Coal to Ethylene Glycol and Its Related Technology, State Key Laboratory of Structural Chemistry, Center for Excellence in Molecular Synthesis, Fujian Institute of Research on the Structure of Matter, …

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Better Together: Catalyzing Innovation in Organic Synthesis via Academic-Industrial Consortia

Jesús Alcázar, Edward A. Anderson, Huw M. L. Davies, Rio Febrian et autres

A t what became one of the most famous speeches in his career, in 1962, U.S. President John F. Kennedy issued a challenge to his nation to do what would be considered near impossible in the 20th century: land humans on the …

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How Can Academia Help Industry Reduce the Footprint of Chemicals Manufacture?

Edouard Godineau, Fabrice Gallou, Olivier Enger, Franziska Ewald et autres

Industrial representatives from the Swiss chemistry ecosystem met to formulate unmet needs in the field of sustainability and share the content of the exchange. The aim is to spark inspiration and trigger ambitious and pre-competitive projects collectively at the interface of the …

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Abstract 3938: Discovery of a novel small molecule inhibitor of the YAP1/TAZ-TEAD transcriptional complex

Casey J. Moure, Christopher Sondey, Mangeng Cheng, My Sam Mansueto et autres

Abstract Hippo pathway alterations in human cancers often result in dephosphorylation of yes-associated protein (YAP1) and its paralog TAZ (WWTR1), allowing the formation of an active complex with transcriptional enhanced associate domain transcription factors (TEADs). This complex formation results in the activation …

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Structure-Guided Discovery of Aminoquinazolines as Brain-Penetrant and Selective LRRK2 Inhibitors

Mitchell H. Keylor, Anmol Gulati, Solomon D. Kattar, Rebecca Johnson et autres

The leucine-rich repeat kinase 2 (LRRK2) protein has been genetically and functionally linked to Parkinson’s disease (PD), a disabling and progressive neurodegenerative disorder whose current therapies are limited in scope and efficacy. In this report, we describe a rigorous hit-to-lead optimization campaign …

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Development of Scalable Routes to 1-Bicyclo[1.1.1]pentylpyrazoles

Cayetana Zárate, Michael J. Ardolino, Gregori J. Morriello, Kaitlyn M. Logan et autres

The application of bicyclo[1.1.1]pentanes (BCPs) as phenyl bioisosteres has garnered significant attention, as these structural motifs can improve the physiochemical profiles of drug candidates. Despite the potential of using 1-bicyclo[1.1.1]pentylpyrazoles (BCPPs) as 1-phenylpyrazole bioisosteres, this area remains underexplored because of the relative …

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Ni(I)–X Complexes Bearing a Bulky α-Diimine Ligand: Synthesis, Structure, and Superior Catalytic Performance in the Hydrogen Isotope Exchange in Pharmaceuticals

Cayetana Zárate, Haifeng Yang, Máté J. Bezdek, David Hesk et autres

The synthesis and spectroscopic characterization of a family of Ni–X (X = Cl, Br, I, H) complexes supported by the bulky α-diimine chelate N, N ′-bis(1 R,2 R,3 R,5 S )-(−)-isopinocampheyl-2,3-butanediimine ( ipc ADI) are described. Diimine-supported, three-coordinate nickel(I)–X complexes have been …

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CCDC 1904728: Experimental Crystal Structure Determination

Cayetana Zárate, Haifeng Yang, Máté J. Bezdek, David Hesk et autres

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, …

CCDC 1904724: Experimental Crystal Structure Determination

Cayetana Zárate, Haifeng Yang, Máté J. Bezdek, David Hesk et autres

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, …