Andrew Morley | University of Salford (original) (raw)

Papers by Andrew Morley

Research paper thumbnail of Allyloxycarbonyl—a useful protecting group for phenolic amino acids and applications on solid support

Tetrahedron Letters, Sep 1, 2000

Bis-protection of phenolic amino acids can be achieved in a one-pot procedure using allyl chlorof... more Bis-protection of phenolic amino acids can be achieved in a one-pot procedure using allyl chloroformate. Subsequent immobilisation via the free acid onto solid support then permits the carbonate protecting group to be selectively removed under mild conditions.

Research paper thumbnail of Abstract 445: A next generation TEAD inhibitor with refined isoform specificity for superior safety & efficacy

Cancer Research, Apr 4, 2023

The Hippo pathway is an important regulator of cell proliferation and one of the last major oncog... more The Hippo pathway is an important regulator of cell proliferation and one of the last major oncogenic pathways not yet extensively targeted in precision oncology. The Hippo pathway is executed by the YAP1/TAZ (WWTR1) co-activators and the TEAD family of transcription factors, which consists of four paralogs (TEAD1-4) with both redundant and unique functions. The transcriptional targets of TEADs include genes playing tumor-promoting roles, including pro-proliferative, immunosuppressive, and anti-apoptotic genes. A growing body of research points to the central importance of the Hippo pathway as a key driver of oncogenesis and as key resistance mechanism to inhibitors of the MAPK pathway or its upstream activators, such as receptor tyrosine kinases. Sporos BioDiscovery has developed novel inhibitors that reversibly bind to the palmitoylation site of TEAD transcription factors to block Hippo pathway activity. Sporos BioDiscovery’s internal bioinformatic insights were leveraged to fine tune the inhibitory activity against the four TEAD paralogs, to maximize efficacy and minimize toxicity. Key characteristics of the SPR1 TEAD inhibitors: (i) low nM, single-agent activity against multiple TEAD-dependent cell lines in vitro in established Hippo-pathway hyperactive mesothelioma cell lines as well as in several non-mesothelioma, cell lines without any obvious lesions in the upstream components of the Hippo pathway. (ii) activity against multiple tumor models in vivo with tumor regression observed even in large established tumors, a feat not previously reported with any other TEAD inhibitor. (iii) strong interactions with inhibitors of the MAPK pathway and inhibitors of its upstream activators, such as RTKs. (iv) favorable ADME profile in rodents, dogs and NHPs, as well as a favorable safety profile. In sum, SPR1 presents monotherapy opportunities in ultra-responder populations based on internal bioinformatic insights, while broader potential exists as an adjuvant for precision oncology targeted therapies, particularly within the MAPK pathway and its upstream activators. Citation Format: Florian Muller, Erkan Baloglu, Andrew D. Morley, Deepavali Chakravarti, Selvi Kunnimalaiyaan, Jeno Gyruis, Sharon Shacham. A next generation TEAD inhibitor with refined isoform specificity for superior safety & efficacy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 445.

Research paper thumbnail of A synthesis of herboxidiene

Journal of the Chemical Society, 1999

ABSTRACT

Research paper thumbnail of ChemInform Abstract: Stereoselective Cycloadditions of Chiral Acylnitroso Compounds. An Approach to Carbapenem Synthesis

Research paper thumbnail of Optimisation and synthesis of libraries derived from phenolic amino acid scaffolds

Tetrahedron Letters, Sep 1, 2000

Research paper thumbnail of ChemInform Abstract: A Synthesis of Herboxidiene

Research paper thumbnail of Structure-Based Design of Protein Tyrosine Phosphatase-1B Inhibitors

ChemInform, Sep 27, 2005

Using structure-based design, a new class of inhibitors of protein tyrosine phosphatase-1B (PTP1B... more Using structure-based design, a new class of inhibitors of protein tyrosine phosphatase-1B (PTP1B) has been identified, which incorporate the 1,2,5-thiadiazolidin-3-one-1,1-dioxide template.

Research paper thumbnail of ChemInform Abstract: A Stereoselective Synthesis of trans-1,2-Disubstituted Alkenes Based on the Condensation of Aldehydes with Metallated 1-Phenyl-1H-tetrazol-5-yl Sulfones

ChemInform, Jun 23, 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Research paper thumbnail of A Stereoselective Synthesis of<i>trans</i>-1,2-Disubstituted Alkenes Based on the Condensation of Aldehydes with Metallated 1-Phenyl-1<i>H</i>-tetrazol-5-yl Sulfones

Synlett, 1998

letter, Synlett 1998; 1998(1): 26-28 DOI: 10.1055/s-1998-1570. © Georg Thieme Verlag, Rüdigerstr.... more letter, Synlett 1998; 1998(1): 26-28 DOI: 10.1055/s-1998-1570. © Georg Thieme Verlag, Rüdigerstr. 14, 70469 Stuttgart, Germany. All rights reserved. This journal, including all individual contributions and illustrations published ...

Research paper thumbnail of Phenyl thiophene carboxamide compounds as inhibitors of the enzyme IKK-2

Research paper thumbnail of Substituted bicyclic compounds

Research paper thumbnail of Pteridine Derivatives and their Use as Cathespin Inhibitors

Research paper thumbnail of INHIBITORS OF c-AMP PHOSPHODIESTERASE AND TNF

Research paper thumbnail of Bicyclic Compounds and Their Use as Integrin Receptor Ligands

Research paper thumbnail of Heterocyclic Amide Derivatives as Inhibitors of Glycogen Phosphorylase

Research paper thumbnail of Indole-amide derivatives and their use as glycogen phosphorylase inhibitors

Research paper thumbnail of INHIBITORS OF c-AMP PHOSPHODIESTERASE

Research paper thumbnail of Thiophene carboxamide compounds as inhibitors of enzyme IKK-2

Research paper thumbnail of Heterocyclic amide derivatives as inhibitors of glycogen phoshorylase

Research paper thumbnail of human beta-II tryptase in complex with 4-(3-Aminomethyl-phenyl)- piperidin-1-yl-(5-phenethyl- pyridin-3-yl)-methanone

Research paper thumbnail of Allyloxycarbonyl—a useful protecting group for phenolic amino acids and applications on solid support

Tetrahedron Letters, Sep 1, 2000

Bis-protection of phenolic amino acids can be achieved in a one-pot procedure using allyl chlorof... more Bis-protection of phenolic amino acids can be achieved in a one-pot procedure using allyl chloroformate. Subsequent immobilisation via the free acid onto solid support then permits the carbonate protecting group to be selectively removed under mild conditions.

Research paper thumbnail of Abstract 445: A next generation TEAD inhibitor with refined isoform specificity for superior safety & efficacy

Cancer Research, Apr 4, 2023

The Hippo pathway is an important regulator of cell proliferation and one of the last major oncog... more The Hippo pathway is an important regulator of cell proliferation and one of the last major oncogenic pathways not yet extensively targeted in precision oncology. The Hippo pathway is executed by the YAP1/TAZ (WWTR1) co-activators and the TEAD family of transcription factors, which consists of four paralogs (TEAD1-4) with both redundant and unique functions. The transcriptional targets of TEADs include genes playing tumor-promoting roles, including pro-proliferative, immunosuppressive, and anti-apoptotic genes. A growing body of research points to the central importance of the Hippo pathway as a key driver of oncogenesis and as key resistance mechanism to inhibitors of the MAPK pathway or its upstream activators, such as receptor tyrosine kinases. Sporos BioDiscovery has developed novel inhibitors that reversibly bind to the palmitoylation site of TEAD transcription factors to block Hippo pathway activity. Sporos BioDiscovery’s internal bioinformatic insights were leveraged to fine tune the inhibitory activity against the four TEAD paralogs, to maximize efficacy and minimize toxicity. Key characteristics of the SPR1 TEAD inhibitors: (i) low nM, single-agent activity against multiple TEAD-dependent cell lines in vitro in established Hippo-pathway hyperactive mesothelioma cell lines as well as in several non-mesothelioma, cell lines without any obvious lesions in the upstream components of the Hippo pathway. (ii) activity against multiple tumor models in vivo with tumor regression observed even in large established tumors, a feat not previously reported with any other TEAD inhibitor. (iii) strong interactions with inhibitors of the MAPK pathway and inhibitors of its upstream activators, such as RTKs. (iv) favorable ADME profile in rodents, dogs and NHPs, as well as a favorable safety profile. In sum, SPR1 presents monotherapy opportunities in ultra-responder populations based on internal bioinformatic insights, while broader potential exists as an adjuvant for precision oncology targeted therapies, particularly within the MAPK pathway and its upstream activators. Citation Format: Florian Muller, Erkan Baloglu, Andrew D. Morley, Deepavali Chakravarti, Selvi Kunnimalaiyaan, Jeno Gyruis, Sharon Shacham. A next generation TEAD inhibitor with refined isoform specificity for superior safety &amp; efficacy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 445.

Research paper thumbnail of A synthesis of herboxidiene

Journal of the Chemical Society, 1999

ABSTRACT

Research paper thumbnail of ChemInform Abstract: Stereoselective Cycloadditions of Chiral Acylnitroso Compounds. An Approach to Carbapenem Synthesis

Research paper thumbnail of Optimisation and synthesis of libraries derived from phenolic amino acid scaffolds

Tetrahedron Letters, Sep 1, 2000

Research paper thumbnail of ChemInform Abstract: A Synthesis of Herboxidiene

Research paper thumbnail of Structure-Based Design of Protein Tyrosine Phosphatase-1B Inhibitors

ChemInform, Sep 27, 2005

Using structure-based design, a new class of inhibitors of protein tyrosine phosphatase-1B (PTP1B... more Using structure-based design, a new class of inhibitors of protein tyrosine phosphatase-1B (PTP1B) has been identified, which incorporate the 1,2,5-thiadiazolidin-3-one-1,1-dioxide template.

Research paper thumbnail of ChemInform Abstract: A Stereoselective Synthesis of trans-1,2-Disubstituted Alkenes Based on the Condensation of Aldehydes with Metallated 1-Phenyl-1H-tetrazol-5-yl Sulfones

ChemInform, Jun 23, 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Research paper thumbnail of A Stereoselective Synthesis of<i>trans</i>-1,2-Disubstituted Alkenes Based on the Condensation of Aldehydes with Metallated 1-Phenyl-1<i>H</i>-tetrazol-5-yl Sulfones

Synlett, 1998

letter, Synlett 1998; 1998(1): 26-28 DOI: 10.1055/s-1998-1570. © Georg Thieme Verlag, Rüdigerstr.... more letter, Synlett 1998; 1998(1): 26-28 DOI: 10.1055/s-1998-1570. © Georg Thieme Verlag, Rüdigerstr. 14, 70469 Stuttgart, Germany. All rights reserved. This journal, including all individual contributions and illustrations published ...

Research paper thumbnail of Phenyl thiophene carboxamide compounds as inhibitors of the enzyme IKK-2

Research paper thumbnail of Substituted bicyclic compounds

Research paper thumbnail of Pteridine Derivatives and their Use as Cathespin Inhibitors

Research paper thumbnail of INHIBITORS OF c-AMP PHOSPHODIESTERASE AND TNF

Research paper thumbnail of Bicyclic Compounds and Their Use as Integrin Receptor Ligands

Research paper thumbnail of Heterocyclic Amide Derivatives as Inhibitors of Glycogen Phosphorylase

Research paper thumbnail of Indole-amide derivatives and their use as glycogen phosphorylase inhibitors

Research paper thumbnail of INHIBITORS OF c-AMP PHOSPHODIESTERASE

Research paper thumbnail of Thiophene carboxamide compounds as inhibitors of enzyme IKK-2

Research paper thumbnail of Heterocyclic amide derivatives as inhibitors of glycogen phoshorylase

Research paper thumbnail of human beta-II tryptase in complex with 4-(3-Aminomethyl-phenyl)- piperidin-1-yl-(5-phenethyl- pyridin-3-yl)-methanone