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29 results on '"Critton, David"'

1. Discovery of Novel TLR7 Agonists as Systemic Agent for Combination With aPD1 for Use in Immuno-oncology

Author

Poudel, Yam B., primary, He, Liqi, additional, Cox, Matthew, additional, Zhang, Qian, additional, Johnson, Walter L., additional, Cong, Qiang, additional, Cheng, Heng, additional, Chowdari, Naidu S., additional, Tarby, Christine, additional, Donnell, Andrew F., additional, Broekema, Matthais, additional, O’Malley, Daniel P., additional, Zhang, Yong, additional, A. M. Subbaiah, Murugaiah, additional, Kumar, Boda Vijay, additional, Subramani, Lakshumanan, additional, Wang, Bei, additional, Li, Yi-Xin, additional, Sivaprakasam, Prasanna, additional, Critton, David, additional, Mulligan, Dawn, additional, Sandhu, Bhupindar, additional, Xie, Chunshan, additional, Ramakrishnan, Radha, additional, Nagar, Jignesh, additional, Dudhgaonkar, Shailesh, additional, Oderinde, Martins S., additional, Murtaza, Anwar, additional, Schieven, Gary L., additional, Mathur, Arvind, additional, Gavai, Ashvinikumar V., additional, Vite, Gregory, additional, and Gangwar, Sanjeev, additional

Published
2024
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2. Identification and Optimization of Small Molecule Pyrazolopyrimidine TLR7 Agonists for Applications in Immuno-oncology.

Author

He, Liqi, Zhang, Meng Yao, Cox, Matthew, Zhang, Qian, Donnell, Andrew F., Zhang, Yong, Tarby, Christine, Gill, Patrice, Subbaiah, Murugaiah A. M., Ramar, Thangeswaran, Reddy, Maheswara, Puttapaka, Vijaya, Li, Yi-Xin, Sivaprakasam, Prasanna, Critton, David, Mulligan, Dawn, Xie, Chunshan, Ramakrishnan, Radha, Nagar, Jignesh, and Dudhgaonkar, Shailesh

Published
2024
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3. VISTA is an acidic pH-selective ligand for PSGL-1

Author

Johnston, Robert J., Su, Linhui Julie, Pinckney, Jason, Critton, David, Boyer, Eric, Krishnakumar, Arathi, and Corbett, Martin

Subjects
T cells -- Physiological aspects -- Genetic aspects, Ligands (Biochemistry) -- Physiological aspects -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Co-inhibitory immune receptors can contribute to T cell dysfunction in patients with cancer.sup.1,2. Blocking antibodies against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) partially reverse this effect and are becoming standard of care in an increasing number of malignancies.sup.3. However, many of the other axes by which tumours become inhospitable to T cells are not fully understood. Here we report that V-domain immunoglobulin suppressor of T cell activation (VISTA) engages and suppresses T cells selectively at acidic pH such as that found in tumour microenvironments. Multiple histidine residues along the rim of the VISTA extracellular domain mediate binding to the adhesion and co-inhibitory receptor P-selectin glycoprotein ligand-1 (PSGL-1). Antibodies engineered to selectively bind and block this interaction in acidic environments were sufficient to reverse VISTA-mediated immune suppression in vivo. These findings identify a mechanism by which VISTA may engender resistance to anti-tumour immune responses, as well as an unexpectedly determinative role for pH in immune co-receptor engagement. V-domain immunoglobulin suppressor of T cell activation (VISTA) selectively engages P-selectin glycoprotein ligand-1 (PSGL-1) and suppresses T cells at acidic pH similar to those in tumour microenvironments, thereby mediating resistance to anti-tumour immune responses., Author(s): Robert J. Johnston [sup.1] , Linhui Julie Su [sup.2] , Jason Pinckney [sup.3] , David Critton [sup.4] , Eric Boyer [sup.1] , Arathi Krishnakumar [sup.5] , Martin Corbett [sup.6] [...]

Published
2019
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4. Synthesis and biological evaluation of biaryl alkyl ethers as inhibitors of IDO1

Author

Markwalder, Jay A., primary, Balog, Aaron J., additional, Williams, David K., additional, Nara, Susheel J., additional, Reddy, Ratnakar, additional, Roy, Saumya, additional, Kanyaboina, Yadagiri, additional, Li, Xin, additional, Johnston, Kathy, additional, Fan, Yi, additional, Lewis, Hal, additional, Marsilio, Frank, additional, Yan, Chunhong, additional, Critton, David, additional, Newitt, John A., additional, Traeger, Sarah C., additional, Wu, Dauh-Rurng, additional, Jure-Kunkel, Maria N., additional, Jayaraman, Lata, additional, Lin, Tai-An, additional, Sinz, Michael W., additional, Hunt, John T., additional, and Seitz, Steven P., additional

Published
2023
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5. Optimization of 4H-pyrrolo[3,2-d]thiazole based antagonists of toll-like receptors 7 and 8 (TLR7/8) for the treatment of lupus

Author

Ratna Kumar, Sreekantha, primary, Laxman, Pasunoori, primary, Hegde, Subramanya, primary, Reddy, Anupama, primary, Barre, Raju, primary, Kumar Anumula, Rushith, primary, Posy, Shana, primary, Critton, David, primary, Mathur, Arvind, primary, Subramaniam, Srinath, primary, Reddy BhimiReddy, Satyanaraya, primary, Dudhgaonkar, Shailesh, primary, Gary, Schieven, primary, Ruepp, Stefan, primary, Macor, John, primary, and J Dyckman, Alaric, primary

Published
2022
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6. Optimization of 4H-pyrrolo[3,2-d]thiazole based antagonists of toll-like receptors 7 and 8 (TLR7/8) for the treatment of lupus

Author

K. Sreekantha, Ratna, primary, Pasunoori, Laxman, primary, Hegde, Subramanya, primary, KR Reddy, Anupama, primary, Barre, Raju, primary, Kumar Anumula, Rushith, primary, Posy, Shana, primary, Critton, David, primary, Mathur, Arvind, primary, Subramaniam, Srinath, primary, Reddy BhimiReddy, Satyanaraya, primary, Dudhgaonkar, Shailesh, primary, Gary, Schieven, primary, Ruepp, Stefan, primary, Macor, John, primary, and J Dyckman, Alaric, primary

Published
2022
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7. Identification of 2-Pyridinylindole-Based Dual Antagonists of Toll-like Receptors 7 and 8 (TLR7/8)

Author

Sreekantha, Ratna Kumar, primary, Mussari, Christopher P., additional, Dodd, Dharmpal S., additional, Pasunoori, Laxman, additional, Hegde, Subramanya, additional, Posy, Shana L., additional, Critton, David, additional, Ruepp, Stefan, additional, Subramanian, Murali, additional, Salter-Cid, Luisa M., additional, Tagore, Debarati Mazumder, additional, Sarodaya, Sanket, additional, Dudhgaonkar, Shailesh, additional, Poss, Michael A., additional, Schieven, Gary L., additional, Carter, Percy H., additional, Macor, John E., additional, and Dyckman, Alaric J., additional

Published
2022
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8. Identification of trisubstituted pyrazoles as potent and selective dual antagonists of toll-like receptors 7 and 8 (TLR 7/8) for the treatment of lupus

Author

Pasunoori, Laxman, primary, K. Sreekantha, Ratna, primary, Pitani, Srinivas, primary, Bhogadi, Vikram, primary, KR Reddy, Anupama, primary, Kumar Anumula, Rushith, primary, Sistla, Ramesh, primary, Posy, Shana, primary, Critton, David, primary, Mathur, Arvind, primary, Karmakar, Ananta, primary, Basha, Mushkin, primary, Reddy BhimiReddy, Satyanaraya, primary, Dudhgaonkar, Shailesh, primary, Leonard Schieven, Gary, primary, Ruepp, Stefan, primary, Macor, John, primary, and J Dyckman, Alaric, primary

Published
2022
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9. Identification of trisubstituted pyrazoles as potent and selective dual antagonists of toll-like receptors 7 and 8 (TLR 7/8) for the treatment of lupus

Author

Laxman, Pasunoori, primary, Ratna Kumar, Sreekantha, primary, Pitani, Srinivas, primary, Bhogadi, Vikram, primary, Reddy, Anupama, primary, Kumar Anumula, Rushith, primary, Sistla, Ramesh, primary, Posy, Shana, primary, Critton, David, primary, Mathur, Arvind, primary, Karmakar, Ananta, primary, Basha, Mushkin, primary, Reddy BhimiReddy, Satyanaraya, primary, Dudhgaonkar, Shailesh, primary, Schieven, Gary, primary, Ruepp, Stefan, primary, Macor, John, primary, and Dyckman, Alaric, primary

Published
2022
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11. Discovery of Potent and Orally Bioavailable Small Molecule Antagonists of Toll-like Receptors 7/8/9 (TLR7/8/9)

Author

Mussari, Christopher P., primary, Dodd, Dharmpal S., additional, Sreekantha, Ratna Kumar, additional, Pasunoori, Laxman, additional, Wan, Honghe, additional, Posy, Shana L., additional, Critton, David, additional, Ruepp, Stefan, additional, Subramanian, Murali, additional, Watson, Andrew, additional, Davies, Paul, additional, Schieven, Gary L., additional, Salter-Cid, Luisa M., additional, Srivastava, Ratika, additional, Tagore, Debarati Mazumder, additional, Dudhgaonkar, Shailesh, additional, Poss, Michael A., additional, Carter, Percy H., additional, and Dyckman, Alaric J., additional

Published
2020
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12. Discovery of Pyridazinone and Pyrazolo[1,5-a]pyridine Inhibitors of C-Terminal Src Kinase

Author

O’Malley, Daniel P., primary, Ahuja, Vijay, additional, Fink, Brian, additional, Cao, Carolyn, additional, Wang, Cindy, additional, Swanson, Jesse, additional, Wee, Susan, additional, Gavai, Ashvinikumar V., additional, Tokarski, John, additional, Critton, David, additional, Paiva, Anthony A., additional, Johnson, Benjamin M., additional, Szapiel, Nicolas, additional, and Xie, Dianlin, additional

Published
2019
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13. Abstract 1548: Acidic pH selective binding of VISTA to PSGL-1 and anti-tumor activity of combined VISTA and PD-1 blockade

Author

Johnston, Robert J., primary, Su, Linhui Julie, additional, Pinckney, Jason, additional, Critton, David, additional, Krishnakumar, Arathi, additional, Corbett, Martin, additional, Rankin, Andrew, additional, DiBella, Rose A., additional, Campbell, Lynne, additional, Deng, Xiaodi, additional, Chen, Haibin, additional, Kozhich, Alexander, additional, Holloway, Jim, additional, Yang, Zheng, additional, Rakestraw, Ginger, additional, Quigley, Michael, additional, and Korman, Alan J., additional

Published
2019
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15. Structural basis of substrate recognition by hematopoietic tyrosine phosphatase

Author

Critton, David A., Tortajada, Antoni, Stetson, Geoffrey, Peti, Wolfgang, and Page, Rebecca

Subjects
Enzyme binding -- Analysis, Phosphatases -- Chemical properties, Tyrosine -- Chemical properties, Biological sciences, Chemistry
Abstract

Multiple techniques are utilized to assess the role of kinase interaction motif-protein tyrosine phosphatase (KIM-PTP) specific residues to understand the molecular basis of substrate recognition by HePTP at the active site. The findings for the structures establish the important role of hematopoietic tyrosine phosphatase (HePTP) T106 to control HePTP specificity to only those substrates which are able to interact with KIM-PTPs via the KIM.

Published
2008

19. Inhibition of Hematopoietic Protein Tyrosine Phosphatase Augments and Prolongs ERK1/2 and p38 Activation

Author

Tautz, Lutz, primary, Sergienko, Eduard, additional, Xu, Jian, additional, Liu, Wallace, additional, Dahl, Russell, additional, Critton, David, additional, Su, Ying, additional, Brown, Brock, additional, Chan, Xochella, additional, Yang, Li, additional, Bobkova, Ekaterina, additional, Vasile, Stefan, additional, Yuan, Hongbin, additional, Rascon, Justin, additional, Colayco, Sharon, additional, Sidique, Shyama, additional, Cosford, Nicholas, additional, Chung, Thomas, additional, Mustelin, Tomas, additional, Page, Rebecca, additional, and Lombroso, Paul, additional

Published
2012
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20. Inhibition of Hematopoietic Protein Tyrosine Phosphatase Augments and Prolongs ERK1/2 and p38 Activation

Author

Sergienko, Eduard, primary, Xu, Jian, additional, Liu, Wallace H., additional, Dahl, Russell, additional, Critton, David A., additional, Su, Ying, additional, Brown, Brock T., additional, Chan, Xochella, additional, Yang, Li, additional, Bobkova, Ekaterina V., additional, Vasile, Stefan, additional, Yuan, Hongbin, additional, Rascon, Justin, additional, Colayco, Sharon, additional, Sidique, Shyama, additional, Cosford, Nicholas D. P., additional, Chung, Thomas D. Y., additional, Mustelin, Tomas, additional, Page, Rebecca, additional, Lombroso, Paul J., additional, and Tautz, Lutz, additional

Published
2011
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22. Inhibition of the Hematopoietic Protein Tyrosine Phosphatase by Phenoxyacetic Acids

Author

Bobkova, Ekaterina V., primary, Liu, Wallace H., additional, Colayco, Sharon, additional, Rascon, Justin, additional, Vasile, Stefan, additional, Gasior, Carlton, additional, Critton, David A., additional, Chan, Xochella, additional, Dahl, Russell, additional, Su, Ying, additional, Sergienko, Eduard, additional, Chung, Thomas D. Y., additional, Mustelin, Tomas, additional, Page, Rebecca, additional, and Tautz, Lutz, additional

Published
2010
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25. Crystal structure of a BRAF kinase domain monomer explains basis for allosteric regulation.

Author

Thevakumaran, Neroshan, Lavoie, Hugo, Critton, David A, Tebben, Andrew, Marinier, Anne, Sicheri, Frank, and Therrien, Marc

Subjects
CRYSTAL structure, ALLOSTERIC regulation, CRYSTALLOGRAPHY, PHYSIOLOGICAL control systems, MONOMERS
Abstract

Reported RAF kinase domain structures adopt a side-to-side dimer configuration reflective of an 'on' state that underpins an allosteric mechanism of regulation. Atomic details of the monomer 'off' state have been elusive. Reinspection of the BRAF kinase domain structures revealed that sulfonamide inhibitors induce features of an off state, primarily a laterally displaced helix αC stabilized by the activation segment helix 1 (AS-H1). These features correlated with the ability of sulfonamides to disrupt human BRAF homodimers in cells, in vitro and in crystals yielding a structure of BRAF in a monomer state. The crystal structure revealed exaggerated, nonproductive positions of helix αC and AS-H1, the latter of which is the target of potent BRAF oncogenic mutations. Together, this work provides formal proof of an allosteric link between the RAF dimer interface, the activation segment and the catalytic infrastructure. [ABSTRACT FROM AUTHOR]

Published
2015
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26. Inhibition of Hematopoietic Protein Tyrosine Phosphatase Augments and Prolongs ERK1/2 and p38 Activation

Author

Sergienko, Eduard, Xu, Jian, Liu, Wallace H., Dahl, Russell, Critton, David A., Su, Ying, Brown, Brock T., Chan, Xochella, Yang, Li, Bobkova, Ekaterina V., Vasile, Stefan, Yuan, Hongbin, Rascon, Justin, Colayco, Sharon, Sidique, Shyama, Cosford, Nicholas D. P., Chung, Thomas D. Y., Mustelin, Tomas, Page, Rebecca, Lombroso, Paul J., and Tautz, Lutz

Abstract

The hematopoietic protein tyrosine phosphatase (HePTP) is implicated in the development of blood cancers through its ability to negatively regulate the mitogen-activated protein kinases (MAPKs) ERK1/2 and p38. Small-molecule modulators of HePTP activity may become valuable in treating hematopoietic malignancies such as T cell acute lymphoblastic leukemia (T-ALL) and acute myelogenous leukemia (AML). Moreover, such compounds will further elucidate the regulation of MAPKs in hematopoietic cells. Although transient activation of MAPKs is crucial for growth and proliferation, prolonged activation of these important signaling molecules induces differentiation, cell cycle arrest, cell senescence, and apoptosis. Specific HePTP inhibitors may promote the latter and thereby may halt the growth of cancer cells. Here, we report the development of a small molecule that augments ERK1/2 and p38 activation in human T cells, specifically by inhibiting HePTP. Structure–activity relationship analysis, in silicodocking studies, and mutagenesis experiments reveal how the inhibitor achieves selectivity for HePTP over related phosphatases by interacting with unique amino acid residues in the periphery of the highly conserved catalytic pocket. Importantly, we utilize this compound to show that pharmacological inhibition of HePTP not only augments but also prolongs activation of ERK1/2 and, especially, p38. Moreover, we present similar effects in leukocytes from mice intraperitoneally injected with the inhibitor at doses as low as 3 mg/kg. Our results warrant future studies with this probe compound that may establish HePTP as a new drug target for acute leukemic conditions.

Published
2012
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27. Discovery of Pyridazinone and Pyrazolo[1,5- a ]pyridine Inhibitors of C-Terminal Src Kinase.

Author

O'Malley DP, Ahuja V, Fink B, Cao C, Wang C, Swanson J, Wee S, Gavai AV, Tokarski J, Critton D, Paiva AA, Johnson BM, Szapiel N, and Xie D

Abstract

C-terminal Src kinase (CSK) functions as a negative regulator of T cell activation through inhibitory phosphorylation of LCK, so inhibitors of CSK are of interest as potential immuno-oncology agents. Screening of an internal kinase inhibitor collection identified pyridazinone lead 1 , and a series of modifications led to optimized compound 13 . Compound 13 showed potent activity in biochemical and cellular assays in vitro and demonstrated the ability to increase T cell proliferation induced by T cell receptor signaling. Compound 13 gave extended exposure in mice upon oral dosing and produced a functional response (decrease in LCK phosphorylation) in mouse spleens at 6 h post dose., Competing Interests: The authors declare the following competing financial interest(s): The authors of this manuscript are employees of Bristol-Myers Squibb., (Copyright © 2019 American Chemical Society.)

Published
2019
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28. Protein tyrosine phosphatases: structure, function, and implication in human disease.

Author

Tautz L, Critton DA, and Grotegut S

Subjects
Catalysis, Catalytic Domain, Crystallography, X-Ray, Humans, Phosphorylation, Substrate Specificity, Tyrosine metabolism, Drug Design, Neoplasms enzymology, Protein Tyrosine Phosphatases chemistry, Protein Tyrosine Phosphatases metabolism
Abstract

Protein tyrosine phosphorylation is a key regulatory mechanism in eukaryotic cell physiology. Aberrant expression or function of protein tyrosine kinases and protein tyrosine phosphatases can lead to serious human diseases, including cancer, diabetes, as well as cardiovascular, infectious, autoimmune, and neuropsychiatric disorders. Here, we give an overview of the protein tyrosine phosphatase superfamily with its over 100 members in humans. We review their structure, function, and implications in human diseases, and discuss their potential as novel drug targets, as well as current challenges and possible solutions to developing therapeutics based on these enzymes.

Published
2013
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29. Inhibition of the Hematopoietic Protein Tyrosine Phosphatase by Phenoxyacetic Acids.

Author

Bobkova EV, Liu WH, Colayco S, Rascon J, Vasile S, Gasior C, Critton DA, Chan X, Dahl R, Su Y, Sergienko E, Chung TD, Mustelin T, Page R, and Tautz L

Abstract

Protein tyrosine phosphatases (PTPs) have only recently become the focus of attention in the search for novel drug targets despite the fact that they play vital roles in numerous cellular processes and are implicated in many human diseases. The hematopoietic protein tyrosine phosphatase (HePTP) is often found dysregulated in preleukemic myelodysplastic syndrome (MDS), as well as in acute myelogenous leukemia (AML). Physiological substrates of HePTP include the mitogen-activated protein kinases (MAPKs) ERK1/2 and p38. Specific modulators of HePTP catalytic activity will be useful for elucidating mechanisms of MAPK regulation in hematopietic cells, and may also provide treatments for hematopoietic malignancies such as AML. Here we report the discovery of phenoxyacetic acids as inhibitors of HePTP. Structure-activity relationship (SAR) analysis and in silico docking studies reveal the molecular basis of HePTP inhibition by these compounds. We also show that these compounds are able to penetrate cell membranes and inhibit HePTP in human T lymphocytes.

Published
2011
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