Search Results - "Chamberlain, Philip"

Development of targeted protein degradation therapeutics by Chamberlain, Philip P., Hamann, Lawrence G.

“…Targeted protein degradation as a therapeutic modality has seen dramatic progress and massive investment in recent years because of the convergence of two key…”
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Linkers for protein degradation by P Chamberlain, Philip

“…The ability to subvert E3 ubiquitin ligases with small-molecule drugs offers tremendous promise for drug discovery. A new study demonstrates how structural and…”
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Targeted Protein Degradation for Kinase Selectivity by Chamberlain, Philip P

“…Targeted protein degradation offers considerable promise for the discovery of new therapeutics. In Cell Chemical Biology, Brand et al. (2019) identify…”
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Structure of the human Cereblon–DDB1–lenalidomide complex reveals basis for responsiveness to thalidomide analogs by Chamberlain, Philip P, Lopez-Girona, Antonia, Miller, Karen, Carmel, Gilles, Pagarigan, Barbra, Chie-Leon, Barbara, Rychak, Emily, Corral, Laura G, Ren, Yan J, Wang, Maria, Riley, Mariko, Delker, Silvia L, Ito, Takumi, Ando, Hideki, Mori, Tomoyuki, Hirano, Yoshinori, Handa, Hiroshi, Hakoshima, Toshio, Daniel, Thomas O, Cathers, Brian E

“…The protein Cereblon, part of an ubiquitin E3 ligase complex, is the target for anticancer thalidomide analogs. The crystal structure of human Cereblon-DDB1…”
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A Cereblon Modulator (CC-220) with Improved Degradation of Ikaros and Aiolos by Matyskiela, Mary E, Zhang, Weihong, Man, Hon-Wah, Muller, George, Khambatta, Godrej, Baculi, Frans, Hickman, Matthew, LeBrun, Laurie, Pagarigan, Barbra, Carmel, Gilles, Lu, Chin-Chun, Lu, Gang, Riley, Mariko, Satoh, Yoshitaka, Schafer, Peter, Daniel, Thomas O, Carmichael, James, Cathers, Brian E, Chamberlain, Philip P

“…The drugs lenalidomide and pomalidomide bind to the protein cereblon, directing the CRL4–CRBN E3 ligase toward the transcription factors Ikaros and Aiolos to…”
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A novel cereblon modulator recruits GSPT1 to the CRL4(CRBN) ubiquitin ligase by Matyskiela, Mary E, Lu, Gang, Ito, Takumi, Pagarigan, Barbra, Lu, Chin-Chun, Miller, Karen, Fang, Wei, Wang, Nai-Yu, Nguyen, Derek, Houston, Jack, Carmel, Gilles, Tran, Tam, Riley, Mariko, Nosaka, Lyn'Al, Lander, Gabriel C, Gaidarova, Svetlana, Xu, Shuichan, Ruchelman, Alexander L, Handa, Hiroshi, Carmichael, James, Daniel, Thomas O, Cathers, Brian E, Lopez-Girona, Antonia, Chamberlain, Philip P

“…Immunomodulatory drugs bind to cereblon (CRBN) to confer differentiated substrate specificity on the CRL4(CRBN) E3 ubiquitin ligase. Here we report the…”
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Crystal structure of the SALL4–pomalidomide–cereblon–DDB1 complex by Matyskiela, Mary E., Clayton, Thomas, Zheng, Xinde, Mayne, Christopher, Tran, Eileen, Carpenter, Aaron, Pagarigan, Barbra, McDonald, Joseph, Rolfe, Mark, Hamann, Lawrence G., Lu, Gang, Chamberlain, Philip P.

“…Thalidomide-dependent degradation of the embryonic transcription factor SALL4 by the CRL4 CRBN E3 ubiquitin ligase is a plausible major driver of thalidomide…”
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Multiple cereblon genetic changes are associated with acquired resistance to lenalidomide or pomalidomide in multiple myeloma by Gooding, Sarah, Ansari-Pour, Naser, Towfic, Fadi, Ortiz Estévez, María, Chamberlain, Philip P., Tsai, Kao-Tai, Flynt, Erin, Hirst, Marissa, Rozelle, Dan, Dhiman, Paula, Neri, Paola, Ramasamy, Karthik, Bahlis, Nizar, Vyas, Paresh, Thakurta, Anjan

“…Emergence of drug resistance to all available therapies is the major challenge to improving survival in myeloma. Cereblon (CRBN) is the essential binding…”
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Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS by Krönke, Jan, Fink, Emma C., Hollenbach, Paul W., MacBeth, Kyle J., Hurst, Slater N., Udeshi, Namrata D., Chamberlain, Philip P., Mani, D. R., Man, Hon Wah, Gandhi, Anita K., Svinkina, Tanya, Schneider, Rebekka K., McConkey, Marie, Järås, Marcus, Griffiths, Elizabeth, Wetzler, Meir, Bullinger, Lars, Cathers, Brian E., Carr, Steven A., Chopra, Rajesh, Ebert, Benjamin L.

“…Lenalidomide is a highly effective treatment for myelodysplastic syndrome (MDS) with deletion of chromosome 5q (del(5q)). Here, we demonstrate that…”
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Molecular glue CELMoD compounds are regulators of cereblon conformation by Watson, Edmond R, Novick, Scott, Matyskiela, Mary E, Chamberlain, Philip P, H de la Peña, Andres, Zhu, Jinyi, Tran, Eileen, Griffin, Patrick R, Wertz, Ingrid E, Lander, Gabriel C

“…Cereblon (CRBN) is a ubiquitin ligase (E3) substrate receptor protein co-opted by CRBN E3 ligase modulatory drug (CELMoD) agents that target therapeutically…”
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SALL4 mediates teratogenicity as a thalidomide-dependent cereblon substrate by Matyskiela, Mary E., Couto, Suzana, Zheng, Xinde, Lu, Gang, Hui, Julia, Stamp, Katie, Drew, Clifton, Ren, Yan, Wang, Maria, Carpenter, Aaron, Lee, Chung-Wein, Clayton, Thomas, Fang, Wei, Lu, Chin-Chun, Riley, Mariko, Abdubek, Polat, Blease, Kate, Hartke, James, Kumar, Gondi, Vessey, Rupert, Rolfe, Mark, Hamann, Lawrence G., Chamberlain, Philip P.

“…Targeted protein degradation via small-molecule modulation of cereblon offers vast potential for the development of new therapeutics. Cereblon-binding…”
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CC-90009, a novel cereblon E3 ligase modulator, targets acute myeloid leukemia blasts and leukemia stem cells by Surka, Christine, Jin, Liqing, Mbong, Nathan, Lu, Chin-Chun, Jang, In Sock, Rychak, Emily, Mendy, Derek, Clayton, Thomas, Tindall, Elizabeth, Hsu, Christy, Fontanillo, Celia, Tran, Eileen, Contreras, Adrian, Ng, Stanley W.K., Matyskiela, Mary, Wang, Kai, Chamberlain, Philip, Cathers, Brian, Carmichael, James, Hansen, Joshua, Wang, Jean C.Y., Minden, Mark D., Fan, Jinhong, Pierce, Daniel W., Pourdehnad, Michael, Rolfe, Mark, Lopez-Girona, Antonia, Dick, John E., Lu, Gang

“…A number of clinically validated drugs have been developed by repurposing the CUL4-DDB1-CRBN-RBX1 (CRL4CRBN) E3 ubiquitin ligase complex with molecular glue…”
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Structure of the human marker of self 5-transmembrane receptor CD47 by Fenalti, Gustavo, Villanueva, Nicolas, Griffith, Mark, Pagarigan, Barbra, Lakkaraju, Sirish Kaushik, Huang, Richard Y.-C., Ladygina, Nadia, Sharma, Alok, Mikolon, David, Abbasian, Mahan, Johnson, Jeffrey, Hadjivassiliou, Haralambos, Zhu, Dan, Chamberlain, Philip P., Cho, Ho, Hariharan, Kandasamy

“…CD47 is the only 5-transmembrane (5-TM) spanning receptor of the immune system. Its extracellular domain (ECD) is a cell surface marker of self that binds…”
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Cereblon modulators: Low molecular weight inducers of protein degradation by Chamberlain, Philip P., Cathers, Brian E.

“…Targeted protein degradation has become an exciting new paradigm in drug discovery with the potential to target new protein families for therapeutic…”
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Evolution of Cereblon-Mediated Protein Degradation as a Therapeutic Modality by Chamberlain, Philip P, D’Agostino, Laura A, Ellis, J. Michael, Hansen, Joshua D, Matyskiela, Mary E, McDonald, Joseph J, Riggs, Jennifer R, Hamann, Lawrence G

“…Many cellular processes and pathways are mediated by the regulation of protein–protein complexes. For example, E3 ubiquitin ligases recruit substrate proteins…”
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Avadomide induces degradation of ZMYM2 fusion oncoproteins in hematologic malignancies by Renneville, Aline, Gasser, Jessica A, Grinshpun, Daniel E, Jean Beltran, Pierre M, Udeshi, Namrata D, Matyskiela, Mary E, Clayton, Thomas, McConkey, Marie, Viswanathan, Kaushik, Tepper, Alexander, Guirguis, Andrew A, Sellar, Rob S, Cotteret, Sophie, Marzac, Christophe, Saada, Véronique, De Botton, Stéphane, Kiladjian, Jean-Jacques, Cayuela, Jean-Michel, Rolfe, Mark, Chamberlain, Philip P, Carr, Steven A, Ebert, Benjamin L

“…Thalidomide analogs exert their therapeutic effects by binding to the CRL4 E3 ubiquitin ligase, promoting ubiquitination and subsequent proteasomal degradation…”
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The Discovery of a Dual TTK Protein Kinase/CDC2-Like Kinase (CLK2) Inhibitor for the Treatment of Triple Negative Breast Cancer Initiated from a Phenotypic Screen by Riggs, Jennifer R, Nagy, Mark, Elsner, Jan, Erdman, Paul, Cashion, Dan, Robinson, Dale, Harris, Roy, Huang, Dehua, Tehrani, Lida, Deyanat-Yazdi, Gordafaried, Narla, Rama Krishna, Peng, Xiaohui, Tran, Tam, Barnes, Leo, Miller, Terra, Katz, Jason, Tang, Yang, Chen, Ming, Moghaddam, Mehran F, Bahmanyar, Sogole, Pagarigan, Barbra, Delker, Silvia, LeBrun, Laurie, Chamberlain, Philip P, Calabrese, Andrew, Canan, Stacie S, Leftheris, Katerina, Zhu, Dan, Boylan, John F

“…Triple negative breast cancer (TNBC) remains a serious unmet medical need with discouragingly high relapse rates. We report here the synthesis and…”
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Cereblon Modulators Target ZBTB16 and Its Oncogenic Fusion Partners for Degradation via Distinct Structural Degrons by Matyskiela, Mary E, Zhu, Jinyi, Baughman, Joshua M, Clayton, Thomas, Slade, Michelle, Wong, Hon Kit, Danga, Kristina, Zheng, Xinde, Labow, Mark, LeBrun, Laurie, Lu, Gang, Chamberlain, Philip P, Thompson, Joel W

“…There is a growing interest in using targeted protein degradation as a therapeutic modality in view of its potential to expand the druggable proteome. One…”
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Small-Molecule Approaches to Targeted Protein Degradation by Faust, Tyler B, Donovan, Katherine A, Yue, Hong, Chamberlain, Philip P, Fischer, Eric S

“…Many essential biological processes are regulated through proximity, from membrane receptor signaling to transcriptional activity. The ubiquitin-proteasome…”
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UBE2G1 governs the destruction of cereblon neomorphic substrates by Lu, Gang, Weng, Stephanie, Matyskiela, Mary, Zheng, Xinde, Fang, Wei, Wood, Scott, Surka, Christine, Mizukoshi, Reina, Lu, Chin-Chun, Mendy, Derek, Jang, In Sock, Wang, Kai, Marella, Mathieu, Couto, Suzana, Cathers, Brian, Carmichael, James, Chamberlain, Philip, Rolfe, Mark

“…The cereblon modulating agents (CMs) including lenalidomide, pomalidomide and CC-220 repurpose the Cul4-RBX1-DDB1-CRBN (CRL4 ) E3 ubiquitin ligase complex to…”
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