Search Results - "Schieven, Gary"

The biology of p38 kinase: a central role in inflammation by Schieven, Gary L

“…The p38 kinase plays a central role in inflammation, and it has been the subject of extensive efforts in both basic research and drug discovery. This review…”
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Novel lung imaging biomarkers and skin gene expression subsetting in dasatinib treatment of systemic sclerosis-associated interstitial lung disease by Martyanov, Viktor, Kim, Grace-Hyun J, Hayes, Wendy, Du, Shuyan, Ganguly, Bishu J, Sy, Oumar, Lee, Sun Ku, Bogatkevich, Galina S, Schieven, Gary L, Schiopu, Elena, Marangoni, Roberta Gonçalves, Goldin, Jonathan, Whitfield, Michael L, Varga, John

“…There are no effective treatments or validated clinical response markers in systemic sclerosis (SSc). We assessed imaging biomarkers and performed gene…”
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Dasatinib, a small-molecule protein tyrosine kinase inhibitor, inhibits T-cell activation and proliferation by Schade, Andrew E., Schieven, Gary L., Townsend, Robert, Jankowska, Anna M., Susulic, Vojkan, Zhang, Rosemary, Szpurka, Hadrian, Maciejewski, Jaroslaw P.

“…Dasatinib is an oral small molecule inhibitor of Abl and Src family tyrosine kinases (SFK), including p56Lck (Lck). Given the central importance of Lck in…”
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Discovery of Non-Nucleotide Small-Molecule STING Agonists via Chemotype Hybridization by Cherney, Emily C, Zhang, Liping, Lo, Julian, Huynh, Tram, Wei, Donna, Ahuja, Vijay, Quesnelle, Claude, Schieven, Gary L, Futran, Alan, Locke, Gregory A, Lin, Zeyu, Monereau, Laura, Chaudhry, Charu, Blum, Jordan, Li, Sha, Fereshteh, Mark, Li-Wang, Bifang, Gangwar, Sanjeev, Pan, Chin, Chong, Colin, Zhu, Xiao, Posy, Shana L, Sack, John S, Zhang, Ping, Ruzanov, Max, Harner, Mary, Akhtar, Fahad, Schroeder, Gretchen M, Vite, Gregory, Fink, Brian

“…The identification of agonists of the stimulator of interferon genes (STING) pathway has been an area of intense research due to their potential to enhance…”
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2-Aminothiazole as a Novel Kinase Inhibitor Template. Structure−Activity Relationship Studies toward the Discovery of N-(2-Chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1- piperazinyl)]-2-methyl-4-pyrimidinyl]amino)]-1,3-thiazole-5-carboxamide (Dasatinib, BMS-354825) as a Potent pan-Src Kinase Inhibitor by Das, Jagabandhu, Chen, Ping, Norris, Derek, Padmanabha, Ramesh, Lin, James, Moquin, Robert V, Shen, Zhongqi, Cook, Lynda S, Doweyko, Arthur M, Pitt, Sidney, Pang, Suhong, Shen, Ding Ren, Fang, Qiong, de Fex, Henry F, McIntyre, Kim W, Shuster, David J, Gillooly, Kathleen M, Behnia, Kamelia, Schieven, Gary L, Wityak, John, Barrish, Joel C

“…2-Aminothiazole (1) was discovered as a novel Src family kinase inhibitor template through screening of our internal compound collection. Optimization through…”
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Rapid Activation of Glutamate Cysteine Ligase following Oxidative Stress by Krejsa, Cecile M., Franklin, Christopher C., White, Collin C., Ledbetter, Jeffrey A., Schieven, Gary L., Kavanagh, Terrance J.

“…Glutamate cysteine ligase (GCL) catalyzes the rate-limiting step in the formation of the cellular antioxidant glutathione (GSH). The GCL holoenzyme consists of…”
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Discovery of Potent and Orally Bioavailable Small Molecule Antagonists of Toll-like Receptors 7/8/9 (TLR7/8/9) by Mussari, Christopher P, Dodd, Dharmpal S, Sreekantha, Ratna Kumar, Pasunoori, Laxman, Wan, Honghe, Posy, Shana L, Critton, David, Ruepp, Stefan, Subramanian, Murali, Watson, Andrew, Davies, Paul, Schieven, Gary L, Salter-Cid, Luisa M, Srivastava, Ratika, Tagore, Debarati Mazumder, Dudhgaonkar, Shailesh, Poss, Michael A, Carter, Percy H, Dyckman, Alaric J

“…The toll-like receptor (TLR) family is an evolutionarily conserved component of the innate immune system, responsible for the early detection of foreign or…”
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Discovery of N-(2-Chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)- piperazin-1-yl)-2-methylpyrimidin-4- ylamino)thiazole-5-carboxamide (BMS-354825), a Dual Src/Abl Kinase Inhibitor with Potent Antitumor Activity in Preclinical Assays by Lombardo, Louis J, Lee, Francis Y, Chen, Ping, Norris, Derek, Barrish, Joel C, Behnia, Kamelia, Castaneda, Stephen, Cornelius, Lyndon A. M, Das, Jagabandhu, Doweyko, Arthur M, Fairchild, Craig, Hunt, John T, Inigo, Ivan, Johnston, Kathy, Kamath, Amrita, Kan, David, Klei, Herbert, Marathe, Punit, Pang, Suhong, Peterson, Russell, Pitt, Sidney, Schieven, Gary L, Schmidt, Robert J, Tokarski, John, Wen, Mei-Li, Wityak, John, Borzilleri, Robert M

“…A series of substituted 2-(aminopyridyl)- and 2-(aminopyrimidinyl)thiazole-5-carboxamides was identified as potent Src/Abl kinase inhibitors with excellent…”
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Discovery of Novel TLR7 Agonists as Systemic Agent for Combination With aPD1 for Use in Immuno-oncology by Poudel, Yam B., He, Liqi, Cox, Matthew, Zhang, Qian, Johnson, Walter L., Cong, Qiang, Cheng, Heng, Chowdari, Naidu S., Tarby, Christine, Donnell, Andrew F., Broekema, Matthais, O’Malley, Daniel P., Zhang, Yong, A. M. Subbaiah, Murugaiah, Kumar, Boda Vijay, Subramani, Lakshumanan, Wang, Bei, Li, Yi-Xin, Sivaprakasam, Prasanna, Critton, David, Mulligan, Dawn, Sandhu, Bhupindar, Xie, Chunshan, Ramakrishnan, Radha, Nagar, Jignesh, Dudhgaonkar, Shailesh, Oderinde, Martins S., Murtaza, Anwar, Schieven, Gary L., Mathur, Arvind, Gavai, Ashvinikumar V., Vite, Gregory, Gangwar, Sanjeev

“…We have designed and developed novel and selective TLR7 agonists that exhibited potent receptor activity in a cell-based reporter assay. In vitro, these…”
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Identification and Optimization of Small Molecule Pyrazolopyrimidine TLR7 Agonists for Applications in Immuno-oncology by 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, Dudhgaonkar, Shailesh, Murtaza, Anwar, Oderinde, Martins S., Schieven, Gary L., Mathur, Arvind, Gavai, Ashvinikumar V., Vite, Gregory, Gangwar, Sanjeev, Poudel, Yam B.

“…Small molecule toll-like receptor (TLR) 7 agonists have gathered considerable interest as promising therapeutic agents for applications in cancer…”
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Identification of 2‑Pyridinylindole-Based Dual Antagonists of Toll-like Receptors 7 and 8 (TLR7/8) by Sreekantha, Ratna Kumar, Mussari, Christopher P., Dodd, Dharmpal S., Pasunoori, Laxman, Hegde, Subramanya, Posy, Shana L., Critton, David, Ruepp, Stefan, Subramanian, Murali, Salter-Cid, Luisa M., Tagore, Debarati Mazumder, Sarodaya, Sanket, Dudhgaonkar, Shailesh, Poss, Michael A., Schieven, Gary L., Carter, Percy H., Macor, John E., Dyckman, Alaric J.

“…The toll-like receptors (TLRs) play key roles in activation of the innate immune system. Aberrant activation of TLR7 and TLR8 pathways can occur in the context…”
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Identification of a Potent, Selective, and Efficacious Phosphatidylinositol 3‑Kinase δ (PI3Kδ) Inhibitor for the Treatment of Immunological Disorders by Liu, Qingjie, Shi, Qing, Marcoux, David, Batt, Douglas G, Cornelius, Lyndon, Qin, Lan-Ying, Ruan, Zheming, Neels, James, Beaudoin-Bertrand, Myra, Srivastava, Anurag S, Li, Ling, Cherney, Robert J, Gong, Hua, Watterson, Scott H, Weigelt, Carolyn, Gillooly, Kathleen M, McIntyre, Kim W, Xie, Jenny H, Obermeier, Mary T, Fura, Aberra, Sleczka, Bogdan, Stefanski, Kevin, Fancher, R. M, Padmanabhan, Shweta, RP, Thatipamula, Kundu, Ipsit, Rajareddy, Kallem, Smith, Rodney, Hennan, James K, Xing, Dezhi, Fan, Jingsong, Levesque, Paul C, Ruan, Qian, Pitt, Sidney, Zhang, Rosemary, Pedicord, Donna, Pan, Jie, Yarde, Melissa, Lu, Hao, Lippy, Jonathan, Goldstine, Christine, Skala, Stacey, Rampulla, Richard A, Mathur, Arvind, Gupta, Anuradha, Arunachalam, Pirama Nayagam, Sack, John S, Muckelbauer, Jodi K, Cvijic, Mary Ellen, Salter-Cid, Luisa M, Bhide, Rajeev S, Poss, Michael A, Hynes, John, Carter, Percy H, Macor, John E, Ruepp, Stefan, Schieven, Gary L, Tino, Joseph A

“…PI3Kδ plays an important role controlling immune cell function and has therefore been identified as a potential target for the treatment of immunological…”
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Discovery of potent and efficacious pyrrolopyridazines as dual JAK1/3 inhibitors by Hynes, John, Wu, Hong, Kempson, James, Duan, James J.-W., Lu, Zhonghui, Jiang, Bin, Stachura, Sylwia, Tokarski, John S., Sack, John S., Khan, Javed A., Lippy, Jonathan S., Zhang, Rosemary F., Pitt, Sidney, Shen, Guoxiang, Gillooly, Kate, McIntyre, Kim, Carter, Percy H., Barrish, Joel C., Nadler, Steven G., Salter-Cid, Luisa M., Fura, Aberra, Schieven, Gary L., Pitts, William J., Wrobleski, Stephen T.

“…[Display omitted] A series of potent dual JAK1/3 inhibitors have been developed from a moderately selective JAK3 inhibitor. Substitution at the C6 position of…”
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Discovery of 4-(5-(Cyclopropylcarbamoyl)-2-methylphenylamino)-5-methyl-N-propylpyrrolo[1,2-f][1,2,4]triazine-6-carboxamide (BMS-582949), a Clinical p38α MAP Kinase Inhibitor for the Treatment of Inflammatory Diseases by Liu, Chunjian, Lin, James, Wrobleski, Stephen T, Lin, Shuqun, Hynes, John, Wu, Hong, Dyckman, Alaric J, Li, Tianle, Wityak, John, Gillooly, Kathleen M, Pitt, Sidney, Shen, Ding Ren, Zhang, Rosemary F, McIntyre, Kim W, Salter-Cid, Luisa, Shuster, David J, Zhang, Hongjian, Marathe, Punit H, Doweyko, Arthur M, Sack, John S, Kiefer, Susan E, Kish, Kevin F, Newitt, John A, McKinnon, Murray, Dodd, John H, Barrish, Joel C, Schieven, Gary L, Leftheris, Katerina

“…The discovery and characterization of 7k (BMS-582949), a highly selective p38α MAP kinase inhibitor that is currently in phase II clinical trials for the…”
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Discovery of a JAK1/3 Inhibitor and Use of a Prodrug To Demonstrate Efficacy in a Model of Rheumatoid Arthritis by Spergel, Steven H, Mertzman, Michael E, Kempson, James, Guo, Junqing, Stachura, Sylwia, Haque, Lauren, Lippy, Jonathan S, Zhang, Rosemary F, Galella, Michael, Pitt, Sidney, Shen, Guoxiang, Fura, Aberra, Gillooly, Kathleen, McIntyre, Kim W, Tang, Vicky, Tokarski, John, Sack, John S, Khan, Javed, Carter, Percy H, Barrish, Joel C, Nadler, Steven G, Salter-Cid, Luisa M, Schieven, Gary L, Wrobleski, Stephen T, Pitts, William J

“…The four members of the Janus family of nonreceptor tyrosine kinases play a significant role in immune function. The JAK family kinase inhibitor, tofacitinib…”
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Discovery of pyrrolo[1,2-b]pyridazine-3-carboxamides as Janus kinase (JAK) inhibitors by Duan, James J-W, Lu, Zhonghui, Jiang, Bin, Yang, Bingwei V, Doweyko, Lidia M, Nirschl, David S, Haque, Lauren E, Lin, Shuqun, Brown, Gregory, Hynes, Jr, John, Tokarski, John S, Sack, John S, Khan, Javed, Lippy, Jonathan S, Zhang, Rosemary F, Pitt, Sidney, Shen, Guoxiang, Pitts, William J, Carter, Percy H, Barrish, Joel C, Nadler, Steven G, Salter-Cid, Luisa M, McKinnon, Murray, Fura, Aberra, Schieven, Gary L, Wrobleski, Stephen T

“…A new class of Janus kinase (JAK) inhibitors was discovered using a rationally designed pyrrolo[1,2-b]pyridazine-3-carboxamide scaffold. Preliminary studies…”
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Discovery of ((4-(5-(Cyclopropylcarbamoyl)-2-methylphenylamino)-5-methylpyrrolo[1,2-f][1,2,4]triazine-6-carbonyl)(propyl)carbamoyloxy)methyl-2-(4-(phosphonooxy)phenyl)acetate (BMS-751324), a Clinical Prodrug of p38α MAP Kinase Inhibitor by Liu, Chunjian, Lin, James, Hynes, John, Wu, Hong, Wrobleski, Stephen T, Lin, Shuqun, Dhar, T G Murali, Vrudhula, Vivekananda M, Sun, Jung-Hui, Chao, Sam, Zhao, Rulin, Wang, Bei, Chen, Bang-Chi, Everlof, Gerry, Gesenberg, Christoph, Zhang, Hongjian, Marathe, Punit H, McIntyre, Kim W, Taylor, Tracy L, Gillooly, Kathleen, Shuster, David J, McKinnon, Murray, Dodd, John H, Barrish, Joel C, Schieven, Gary L, Leftheris, Katerina

“…In search for prodrugs to address the issue of pH-dependent solubility and exposure associated with 1 (BMS-582949), a previously disclosed phase II clinical…”
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Design, Synthesis, and Anti-inflammatory Properties of Orally Active 4-(Phenylamino)-pyrrolo[2,1-f][1,2,4]triazine p38α Mitogen-Activated Protein Kinase Inhibitors by Hynes, John, Dyckman, Alaric J, Lin, Shuqun, Wrobleski, Stephen T, Wu, Hong, Gillooly, Kathleen M, Kanner, Steven B, Lonial, Herinder, Loo, Derek, McIntyre, Kim W, Pitt, Sidney, Shen, Ding Ren, Shuster, David J, Yang, XiaoXia, Zhang, Rosemary, Behnia, Kamelia, Zhang, Hongjian, Marathe, Punit H, Doweyko, Arthur M, Tokarski, John S, Sack, John S, Pokross, Matthew, Kiefer, Susan E, Newitt, John A, Barrish, Joel C, Dodd, John, Schieven, Gary L, Leftheris, Katerina

“…A novel structural class of p38 mitogen-activated protein (MAP) kinase inhibitors consisting of substituted 4-(phenylamino)-pyrrolo[2,1-f][1,2,4]triazines has…”
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The identification of novel p38α isoform selective kinase inhibitors having an unprecedented p38α binding mode by Wrobleski, Stephen T., Lin, Shuqun, Murali Dhar, T.G., Dyckman, Alaric J., Li, Tianle, Pitt, Sidney, Zhang, Rosemary, Fan, Yi, Doweyko, Arthur M., Tokarski, John S., Kish, Kevin F., Kiefer, Susan E., Sack, John S., Newitt, John A., Witmer, Mark R., McKinnon, Murray, Barrish, Joel C., Dodd, John H., Schieven, Gary L., Leftheris, Katerina

“…A novel series of p38 MAP kinase inhibitors with high selectivity for the p38α isoform over the other family members including the highly homologous p38β…”
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Synthesis and evaluation of carbamoylmethylene linked prodrugs of BMS-582949, a clinical p38α inhibitor by Liu, Chunjian, Lin, James, Everlof, Gerry, Gesenberg, Christoph, Zhang, Hongjian, Marathe, Punit H., Malley, Mary, Galella, Michael A., Mckinnon, Murray, Dodd, John H., Barrish, Joel C., Schieven, Gary L., Leftheris, Katerina

“…A series of carbamoylmethylene linked prodrugs of 1 (BMS-582949), a clinical p38α inhibitor, were synthesized and evaluated. Though the phosphoryloxymethylene…”
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