Search Results - "Metcalf, Brian"

GBT440 increases haemoglobin oxygen affinity, reduces sickling and prolongs RBC half‐life in a murine model of sickle cell disease by Oksenberg, Donna, Dufu, Kobina, Patel, Mira P., Chuang, Chihyuan, Li, Zhe, Xu, Qing, Silva‐Garcia, Abel, Zhou, Chengjing, Hutchaleelaha, Athiwat, Patskovska, Larysa, Patskovsky, Yury, Almo, Steven C., Sinha, Uma, Metcalf, Brian W., Archer, David R.

“…Summary A major driver of the pathophysiology of sickle cell disease (SCD) is polymerization of deoxygenated haemoglobin S (HbS), which leads to sickling and…”
Get full text

INCB24360 (Epacadostat), a Highly Potent and Selective Indoleamine-2,3-dioxygenase 1 (IDO1) Inhibitor for Immuno-oncology by Yue, Eddy W, Sparks, Richard, Polam, Padmaja, Modi, Dilip, Douty, Brent, Wayland, Brian, Glass, Brian, Takvorian, Amy, Glenn, Joseph, Zhu, Wenyu, Bower, Michael, Liu, Xiangdong, Leffet, Lynn, Wang, Qian, Bowman, Kevin J, Hansbury, Michael J, Wei, Min, Li, Yanlong, Wynn, Richard, Burn, Timothy C, Koblish, Holly K, Fridman, Jordan S, Emm, Tom, Scherle, Peggy A, Metcalf, Brian, Combs, Andrew P

“…A data-centric medicinal chemistry approach led to the invention of a potent and selective IDO1 inhibitor 4f, INCB24360 (epacadostat). The molecular structure…”
Get full text

Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050 by Fridman, Jordan S, Scherle, Peggy A, Collins, Robert, Burn, Timothy C, Li, Yanlong, Li, Jun, Covington, Maryanne B, Thomas, Beth, Collier, Paul, Favata, Margaret F, Wen, Xiaoming, Shi, Jack, McGee, Ryan, Haley, Patrick J, Shepard, Stacey, Rodgers, James D, Yeleswaram, Swamy, Hollis, Greg, Newton, Robert C, Metcalf, Brian, Friedman, Steven M, Vaddi, Kris

“…Inhibiting signal transduction induced by inflammatory cytokines offers a new approach for the treatment of autoimmune diseases such as rheumatoid arthritis…”
Get full text

Discovery of GBT440, an Orally Bioavailable R‑State Stabilizer of Sickle Cell Hemoglobin by Metcalf, Brian, Chuang, Chihyuan, Dufu, Kobina, Patel, Mira P, Silva-Garcia, Abel, Johnson, Carl, Lu, Qing, Partridge, James R, Patskovska, Larysa, Patskovsky, Yury, Almo, Steven C, Jacobson, Matthew P, Hua, Lan, Xu, Qing, Gwaltney, Stephen L, Yee, Calvin, Harris, Jason, Morgan, Bradley P, James, Joyce, Xu, Donghong, Hutchaleelaha, Athiwat, Paulvannan, Kumar, Oksenberg, Donna, Li, Zhe

“…We report the discovery of a new potent allosteric effector of sickle cell hemoglobin, GBT440 (36), that increases the affinity of hemoglobin for oxygen and…”
Get full text

Enantioselective Synthesis of Janus Kinase Inhibitor INCB018424 via an Organocatalytic Aza-Michael Reaction by Lin, Qiyan, Meloni, David, Pan, Yongchun, Xia, Michael, Rodgers, James, Shepard, Stacey, Li, Mei, Galya, Laurine, Metcalf, Brian, Yue, Tai-Yuen, Liu, Pingli, Zhou, Jiacheng

“…An enantioselective synthesis of INCB018424 via organocatalytic asymmetric aza-Michael addition of pyrazoles (16 or 20) to (E)-3-cyclopentylacrylaldehyde (23)…”
Get full text

Preclinical Evaluation of Local JAK1 and JAK2 Inhibition in Cutaneous Inflammation by Fridman, Jordan S., Scherle, Peggy A., Collins, Robert, Burn, Timothy, Neilan, Claire L., Hertel, Denise, Contel, Nancy, Haley, Patrick, Thomas, Beth, Shi, Jack, Collier, Paul, Rodgers, James D., Shepard, Stacey, Metcalf, Brian, Hollis, Gregory, Newton, Robert C., Yeleswaram, Swamy, Friedman, Steven M., Vaddi, Kris

“…JAKs are required for signaling initiated by several cytokines (e.g., IL-4, IL-12, IL-23, thymic stromal lymphopoietin (TSLP), and IFNγ) implicated in the…”
Get full text

Identification of ADAM10 as a major source of HER2 ectodomain sheddase activity in HER2 overexpressing breast cancer cells by Liu, Phillip C.C., Liu, Xiangdong, Li, Yanlong, Covington, Maryanne, Wynn, Richard, Huber, Reid, Hillman, Milton, Yang, Gengjie, Ellis, Dawn, Marando, Cindy, Katiyar, Kamna, Bradley, Jodi, Abremski, Kenneth, Stow, Mark, Rupar, Mark, Zhuo, Jincong, Li, Yun-Long, Lin, Qiyan, Burns, David, Xu, Meizhong, Zhang, Colin, Qian, Ding-Quan, He, Chunhong, Sharief, Vaqar, Weng, Lingkai, Agrios, Costas, Shi, Eric, Metcalf, Brian, Newton, Robert, Friedman, Steven, Yao, Wenqing, Scherle, Peggy A., Hollis, Gregory, Burn, Timothy C.

“…ALL AUTHORS: Phillip C.C. Liu, Xiangdong Liu, Yanlong Li, Maryanne Covington, Richard Wynn, Reid Huber, Milton Hillman, Gengjie Yang, Dawn Ellis, Cindy…”
Get full text

Discovery of INCB10820/PF-4178903, a potent, selective, and orally bioavailable dual CCR2 and CCR5 antagonist by Zheng, Changsheng, Cao, Ganfeng, Xia, Michael, Feng, Hao, Glenn, Joseph, Anand, Rajan, Zhang, Ke, Huang, Taisheng, Wang, Anlai, Kong, Ling, Li, Mei, Galya, Laurine, Hughes, Robert O., Devraj, Rajesh, Morton, Phillip A., Rogier, D. Joseph, Covington, Maryanne, Baribaud, Fred, Shin, Niu, Scherle, Peggy, Diamond, Sharon, Yeleswaram, Swamy, Vaddi, Kris, Newton, Robert, Hollis, Greg, Friedman, Steven, Metcalf, Brian, Xue, Chu-Biao

“…We report the discovery of a potent, selective, and orally bioavailable dual CCR2 and CCR5 antagonist (3 S,4 S)- N-[(1 R,3…”
Get full text

Discovery of INCB3284, a Potent, Selective, and Orally Bioavailable hCCR2 Antagonist by Xue, Chu-Biao, Feng, Hao, Cao, Ganfeng, Huang, Taisheng, Glenn, Joseph, Anand, Rajan, Meloni, David, Zhang, Ke, Kong, Lingquan, Wang, Anlai, Zhang, Yingxin, Zheng, Changsheng, Xia, Michael, Chen, Lihua, Tanaka, Hiroyuki, Han, Qi, Robinson, D. J, Modi, Dilip, Storace, Lou, Shao, Lixin, Sharief, Vaqar, Li, Mei, Galya, Laurine G, Covington, Maryanne, Scherle, Peggy, Diamond, Sharon, Emm, Tom, Yeleswaram, Swamy, Contel, Nancy, Vaddi, Kris, Newton, Robert, Hollis, Greg, Friedman, Steven, Metcalf, Brian

“…We report the identification of 13 (INCB3284) as a potent human CCR2 (hCCR2) antagonist. INCB3284 exhibited an IC50 of 3.7 nM in antagonism of monocyte…”
Get full text

Discovery of a Potent, Selective, and Orally Active Human Epidermal Growth Factor Receptor-2 Sheddase Inhibitor for the Treatment of Cancer by Yao, Wenqing, Zhuo, Jincong, Burns, David M, Xu, Meizhong, Zhang, Colin, Li, Yun-Long, Qian, Ding-Quan, He, Chunhong, Weng, Lingkai, Shi, Eric, Lin, Qiyan, Agrios, Costas, Burn, Timothy C, Caulder, Eian, Covington, Maryanne B, Fridman, Jordan S, Friedman, Steven, Katiyar, Kamna, Hollis, Gregory, Li, Yanlong, Liu, Changnian, Liu, Xiangdong, Marando, Cindy A, Newton, Robert, Pan, Max, Scherle, Peggy, Taylor, Nancy, Vaddi, Kris, Wasserman, Zelda R, Wynn, Richard, Yeleswaram, Swamy, Jalluri, Ravi, Bower, Michael, Zhou, Bing-Bing, Metcalf, Brian

“…The design, synthesis, evaluation, and identification of a novel class of (6S,7S)-N-hydroxy-6-carboxamide-5-azaspiro[2.5]octane-7-carboxamides as the first…”
Get full text

Discrimination of gamma-hydroxybutyrate and ethanol administered separately and as a mixture in rats by Metcalf, Brian R, Stahl, Jeanne M, Allen, Joseph D, Woolfolk, Dedra R, Soto, Paul L

“…The physiological effects of gamma-hydroxybutyrate (GHB) are complex and not yet clearly defined. GHB has been labeled as a recreational drug and is reported…”
Get full text

Inhibition of HIV-1 protease in infected T-lymphocytes by synthetic peptide analogues by Meek, Thomas D, Lambert, Dennis M, Dreyer, Geoffrey B, Carr, Thomas J, Tomaszek, Thaddeus A, Moore, Michael L, Strickler, James E, Debouck, Christine, Hyland, Lawrence J, Matthews, Thomas J, Metcalf, Brian W, Petteway, Stephen R

“…The gag and pol genes of the human immunodeficiency virus type 1 (HIV-1) (ref. 1) are translated as two polyproteins, Pr55gag and Pr160gag-pol (refs 2-6),…”
Get full text

GBT440 Demonstrates High Specificity for Red Blood Cells in Nonclinical Species by Hutchaleelaha, Athiwat, Patel, Mira, Silva, Abel, Oksenberg, Donna, Metcalf, Brian

“…Sickle cell disease (SCD) is caused by a point mutation in the β-globin gene leading to production of hemoglobin S (HbS) that polymerizes upon deoxygenation…”
Get full text

Parsaclisib Is a Next-Generation Phosphoinositide 3-Kinase δ Inhibitor with Reduced Hepatotoxicity and Potent Antitumor and Immunomodulatory Activities in Models of B-Cell Malignancy by Shin, Niu, Stubbs, Matthew, Koblish, Holly, Yue, Eddy W., Soloviev, Maxim, Douty, Brent, Wang, Kathy He, Wang, Qian, Gao, Mingming, Feldman, Patricia, Yang, Gengjie, Hall, Leslie, Hansbury, Michael, O’Connor, Sybil, Leffet, Lynn, Collins, Robert, Katiyar, Kamna, He, Xin, Waeltz, Paul, Collier, Paul, Lu, Jin, Li, Yun-Long, Li, Yanlong, Liu, Phillip C.C., Burn, Timothy, Covington, Maryanne, Diamond, Sharon, Shuey, Dana, Roberts, Alan, Yeleswaram, Swamy, Hollis, Greg, Metcalf, Brian, Yao, Wenqing, Huber, Reid, Combs, Andrew, Newton, Robert, Scherle, Peggy

Get full text

Structures of full-length plasma kallikrein bound to highly specific inhibitors describe a new mode of targeted inhibition by Partridge, James R., Choy, Rebeca M., Silva-Garcia, Abel, Yu, Chul, Li, Zhe, Sham, Hing, Metcalf, Brian

“…[Display omitted] •Co-crystallization of plasma kallikrein with inhibitor reveals a novel binding site.•The class of small molecule inhibitors described are…”
Get full text

Discovery of Potent Competitive Inhibitors of Indoleamine 2,3-Dioxygenase with in Vivo Pharmacodynamic Activity and Efficacy in a Mouse Melanoma Model by Yue, Eddy W, Douty, Brent, Wayland, Brian, Bower, Michael, Liu, Xiangdong, Leffet, Lynn, Wang, Qian, Bowman, Kevin J, Hansbury, Michael J, Liu, Changnian, Wei, Min, Li, Yanlong, Wynn, Richard, Burn, Timothy C, Koblish, Holly K, Fridman, Jordan S, Metcalf, Brian, Scherle, Peggy A, Combs, Andrew P

“…A hydroxyamidine chemotype has been discovered as a key pharmacophore in novel inhibitors of indoleamine 2,3-dioxygenase (IDO). Optimization led to the…”
Get full text

Abstract 2938: In vivo assessment of the combination of the JAK1 selective inhibitor itacitinib with first- and second-generation EGFR inhibitors in models of non-small cell lung cancer by Stubbs, Matthew C., Wen, Xiaoming, Xue, Chu-Biao, Huang, Taisheng, Yao, Wenqing, Metcalf, Brian, Huber, Reid, Scherle, Peggy, Ruggeri, Bruce

“…Abstract Non-small cell lung cancers (NSCLC) make up the majority of lung cancers, and are predominantly driven by aberrant kinase pathway signaling. Oncogenic…”
Get full text

GTx011, an Anti-Sickling Compound, Improves SS Blood Rheology By Reduction of HbS polymerization Via Allosteric Modulation of O2 Affinity by Patel, Mira, Cabrales, Pedro, Dufu, Kobina, Metcalf, Brian, Sinha, Uma

“…Sickle cell disease is caused by a mutation in the β-globin gene leading to production of hemoglobin S (HbS). HbS polymerizes under hypoxic conditions, leading…”
Get full text

Discovery of a novel 2-spiroproline steroid mimetic scaffold for the potent inhibition of 11β-HSD1 by Burns, David M., He, Chunhong, Li, Yun-Long, Zhuo, Jincong, Qian, Ding-Quan, Chen, Lihua, Jalluri, Ravi, Diamond, Sharon, Covington, Maryanne B., Li, Yanlong, Wynn, Richard, Scherle, Peggy, Yeleswaram, Swamy, Hollis, Gregory, Friedman, Steve, Metcalf, Brian, Yao, Wenqing

“…[Display omitted] 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) has been identified as the primary enzyme responsible for the activation of hepatic cortisone…”
Get full text

Discovery of 1′-(1-phenylcyclopropane-carbonyl)-3H-spiro[isobenzofuran-1,3′-pyrrolidin]-3-one as a novel steroid mimetic scaffold for the potent and tissue-specific inhibition of 11β-HSD1 using a scaffold-hopping approach by Zhang, Colin, Xu, Meizhong, He, Chunhong, Zhuo, Jincong, Burns, David M., Qian, Ding-Quan, Lin, Qiyan, Li, Yun-Long, Chen, Lihua, Shi, Eric, Agrios, Costas, Weng, Linkai, Sharief, Vaqar, Jalluri, Ravi, Li, Yanlong, Scherle, Peggy, Diamond, Sharon, Hunter, Deborah, Covington, Maryanne, Marando, Cindy, Wynn, Richard, Katiyar, Kamna, Contel, Nancy, Vaddi, Kris, Yeleswaram, Swamy, Hollis, Gregory, Huber, Reid, Friedman, Steve, Metcalf, Brian, Yao, Wenqing

“…[Display omitted] 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) has been identified as the primary enzyme responsible for the activation of hepatic cortisone…”
Get full text