keyword
MENU ▼
Read by QxMD icon Read
search

Cynomolgus

keyword
https://www.readbyqxmd.com/read/28530802/discovery-of-n-5-fluoropyridin-2-yl-6-methyl-4-pyrimidin-5-yloxy-picolinamide-vu0424238-a-novel-negative-allosteric-modulator-of-metabotropic-glutamate-receptor-subtype-5-selected-for-clinical-evaluation
#1
Andrew S Felts, Alice L Rodriguez, Anna L Blobaum, Ryan D Morrison, Brittney S Bates, Analisa Thompson Gray, Jerri M Rook, Mohammed N Tantawy, Frank W Byers, Sichen Chang, Daryl F Venable, Vincent B Luscombe, Gilles D Tamagnan, Colleen M Niswender, J Scott Daniels, Carrie K Jones, P Jeffrey Conn, Craig W Lindsley, Kyle A Emmitte
Preclinical evidence in support of the potential utility of mGlu5 NAMs for the treatment of a variety of psychiatric and neurodegenerative disorders is extensive, and multiple such molecules have entered clinical trials. Despite some promising results from clinical studies, no small molecule mGlu5 NAM has yet to reach market. Here we present the discovery and evaluation of N-(5-fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide (27, VU0424238), a compound selected for clinical evaluation. Compound 27 is more than 900-fold selective for mGlu5 versus the other mGlu receptors, and binding studies established a Ki value of 4...
May 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28529273/septicemic-invasive-klebsiella-pneumoniae-infection-in-a-cynomolgus-monkey-macaca-fascicularis-with-severe-diffused-suppurative-meningoencephalitis
#2
Kazufumi Kasuya, Kou Takayama, Makiko Bito, Natsumi Shimokubo, Ryosuke Kawashima, Tomoyuki Shibahara
A 2-year-old male cynomolgus monkey (Macaca fascicularis) showed neurological symptoms during quarantine for importation into Japan, and was euthanized due to poor prognosis. Gross anatomical examination revealed a hemorrhagic lesion around the lateral ventricle in the cerebrum. Histologically, severe diffused suppurative meningitis and ventriculitis were detected with numerous Gram-negative bacilli in the cerebrum. Immunohistochemically, the bacilli were positively stained with an antibody against Klebsiella pneumoniae...
May 22, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28528082/discovery-of-bi-135585-an-in-vivo-efficacious-oxazinanone-based-11%C3%AE-hydroxysteroid-dehydrogenase-type-1-inhibitor
#3
Linghang Zhuang, Colin M Tice, Zhenrong Xu, Wei Zhao, Salvacion Cacatian, Yuan-Jie Ye, Suresh B Singh, Peter Lindblom, Brian M McKeever, Paula M Krosky, Yi Zhao, Deepak Lala, Barbara A Kruk, Shi Meng, Lamont Howard, Judith A Johnson, Yuri Bukhtiyarov, Reshma Panemangalore, Joan Guo, Rong Guo, Frank Himmelsbach, Bradford Hamilton, Annette Schuler-Metz, Heike Schauerte, Richard Gregg, Gerard M McGeehan, Katerina Leftheris, David A Claremon
A potent, in vivo efficacious 11β hydroxysteroid dehydrogenase type 1 (11β HSD1) inhibitor (11j) has been identified. Compound 11j inhibited 11β HSD1 activity in human adipocytes with an IC50 of 4.3nM and in primary human adipose tissue with an IC80 of 53nM. Oral administration of 11j to cynomolgus monkey inhibited 11β HSD1 activity in adipose tissue. Compound 11j exhibited >1000× selectivity over other hydroxysteroid dehydrogenases, displays desirable pharmacodynamic properties and entered human clinical trials in 2011...
April 29, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28525759/modeling-rett-syndrome-using-talen-edited-mecp2-mutant-cynomolgus-monkeys
#4
Yongchang Chen, Juehua Yu, Yuyu Niu, Dongdong Qin, Hailiang Liu, Gang Li, Yingzhou Hu, Jiaojian Wang, Yi Lu, Yu Kang, Yong Jiang, Kunhua Wu, Siguang Li, Jingkuan Wei, Jing He, Junbang Wang, Xiaojing Liu, Yuping Luo, Chenyang Si, Raoxian Bai, Kunshan Zhang, Jie Liu, Shaoyong Huang, Zhenzhen Chen, Shuang Wang, Xiaoying Chen, Xinhua Bao, Qingping Zhang, Fuxing Li, Rui Geng, Aibin Liang, Dinggang Shen, Tianzi Jiang, Xintian Hu, Yuanye Ma, Weizhi Ji, Yi Eve Sun
Gene-editing technologies have made it feasible to create nonhuman primate models for human genetic disorders. Here, we report detailed genotypes and phenotypes of TALEN-edited MECP2 mutant cynomolgus monkeys serving as a model for a neurodevelopmental disorder, Rett syndrome (RTT), which is caused by loss-of-function mutations in the human MECP2 gene. Male mutant monkeys were embryonic lethal, reiterating that RTT is a disease of females. Through a battery of behavioral analyses, including primate-unique eye-tracking tests, in combination with brain imaging via MRI, we found a series of physiological, behavioral, and structural abnormalities resembling clinical manifestations of RTT...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28525647/evaluation-of-the-effects-of-tanezumab-a-monoclonal-antibody-against-nerve-growth-factor-on-the-sympathetic-nervous-system-in-adult-cynomolgus-monkeys-macaca-fascicularis-a-stereologic-histomorphologic-and-cardiofunctional-assessment
#5
Patrice Belanger, Paul Butler, Mark Butt, Siddhartha Bhatt, Stephen Foote, David Shelton, Mark Evans, Rosalinda Arends, Susan Hurst, Carlin Okerberg, Thomas Cummings, David Potter, Jill Steidl-Nichols, Mark Zorbas
Tanezumab, a humanized monoclonal antibody against nerve growth factor is in development for treatment of chronic pain. Three nonclinical studies assessed effects of clinically relevant and supratherapeutic doses of tanezumab on the sympathetic nervous system (SNS) of adult nonhuman primates. Study 1 evaluated potential effects of subcutaneous (SC) tanezumab (1.2 mg/kg every 8 weeks [Q8W]) on SNS in cynomolgus monkeys for 3 or 6 months and reversibility or persistence of any effects through a non-dosing/recovery period...
May 19, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28522025/corrigendum-to-genetic-polymorphism-of-cynomolgus-and-rhesus-macaque-cyp2c9-drug-metab-pharmacokinet-30-2015-130-132
#6
Yasuhiro Uno, Akinori Matsushita, Norie Murayama, Hiroshi Yamazaki
No abstract text is available yet for this article.
April 25, 2017: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28516852/effects-of-olanexidine-gluconate-on-preoperative-skin-preparation-an-experimental-study-in-cynomolgus-monkeys
#7
Hikaru Nakata, Yoshie Tsubotani, Takuya Nii, Akifumi Hagi, Yasuhide Inoue, Tadashi Imamura
PURPOSE: To determine the bactericidal efficacy of a new topical antiseptic for preoperative skin preparation, olanexidine gluconate (development code: OPB-2045G), against transient or resident bacterial flora on the skin of cynomolgus monkeys. METHODOLOGY: After measuring baseline bacterial counts on test sites marked on the abdomens, we applied olanexidine, chlorhexidine or povidone-iodine. After 10 min (fast-acting effect) and 6 h (long-lasting effect), bacterial counts were measured again and log10 reductions were calculated...
May 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28516358/mechanistic-modeling-of-the-pharmacodynamic-and-pharmacokinetic-relationship-of-tissue-factor-pathway-inhibitor-neutralizing-antibody-bay-1093884-in-cynomolgus-monkeys
#8
Jian-Ming Gu, Xiao-Yan Zhao, Thomas Schwarz, Joachim Schuhmacher, Andreas Baumann, Elena Ho, Babu Subramanyan, Kathy Tran, Timothy Myles, Chandra Patel, Maria Koellnberger
BAY 1093884 is a fully human monoclonal antibody against the tissue factor pathway inhibitor (TFPI) in development as prophylaxis in patients with hemophilia with or without inhibitors. In vitro, BAY 1093884 binds to human, mouse, and monkey TFPI. The objective of this study was to find a pharmacodynamic (PD) biomarker after administration of BAY 1093884 to normal monkeys. In monkey plasma, BAY 1093884 exhibited an IC50 (concentration that inhibits 50%) of 4.65 and 6.19 nM for free TFPI and diluted prothrombin time (dPT), respectively...
May 17, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28515226/a-neutralizing-anti-g-csfr-antibody-blocks-g-csf-induced-neutrophilia-without-inducing-neutropenia-in-nonhuman-primates
#9
Karen Scalzo-Inguanti, Katherine Monaghan, Kirsten Edwards, Eva Herzog, Danijela Mirosa, Matthew Hardy, Vicki Sorto, Huy Huynh, Steven Rakar, Daria Kurtov, Hal Braley, Nick Wilson, Samantha Busfield, Andrew Nash, Arna Andrews
Neutrophils are the most abundant WBCs and have an essential role in the clearance of pathogens. Tight regulation of neutrophil numbers and their recruitment to sites of inflammation is critical in maintaining a balanced immune response. In various inflammatory conditions, such as rheumatoid arthritis, vasculitis, cystic fibrosis, and inflammatory bowel disease, increased serum G-CSF correlates with neutrophilia and enhanced neutrophil infiltration into inflamed tissues. We describe a fully human therapeutic anti-G-CSFR antibody (CSL324) that is safe and well tolerated when administered via i...
May 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28504465/effects-of-sa237-a-humanized-anti-interleukin-6-receptor-monoclonal-antibody-on-pre-and-postnatal-development-in-cynomolgus-monkey
#10
Ryuichi Katagiri, Kana Ishihara-Hattori, Werner Frings, Jun Amano, Antje Fuchs, Shuichi Chiba
BACKGROUND: SA237 is a humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody in which the constant and variable regions have been engineered for a longer plasma half-life. According to literature, blocking of IL-6 related functions could have an influence on pregnancy sustainment, development of the immune system, and brain growth. METHODS: SA237 effects on dams, embryo-fetal development, parturition and postnatal development were investigated in an enhanced pre- and postnatal development study, in which SA237 was subcutaneously administered to pregnant cynomolgus monkeys at dose levels of 2 or 50 mg/kg once weekly from gestation day 20 until parturition...
May 15, 2017: Birth Defects Res
https://www.readbyqxmd.com/read/28495902/regio-and-stereo-selective-oxidation-of-a-cardiovascular-drug-metoprolol-mediated-by-cytochrome-p450-2d-and-3a-enzymes-in-marmoset-livers
#11
Shotaro Uehahara, Sakura Ishii, Yasuhiro Uno, Takashi Inoue, Erika Sasaki, Hiroshi Yamazaki
A β-blocker metoprolol is one of the in vivo probes for human cytochrome P450 (P450) 2D6. Investigation of non-human primate P450 enzymes helps improve accuracy of the extrapolation of pharmacokinetic data from animals into humans. Common marmosets (Callithrix jacchus) are a potential primate model for preclinical research, but detailed roles of marmoset P450 enzymes in metoprolol oxidations remained unknown. In this study, regio- and stereo-selectivity of metoprolol oxidations by a variety of P450 enzymes in marmoset and human livers were investigated in vitro...
May 11, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28493964/non-human-primate-orthologues-of-tmprss2-cleave-and-activate-the-influenza-virus-hemagglutinin
#12
Pawel Zmora, Paulina Molau-Blazejewska, Stephanie Bertram, Kerstin Walendy-Gnirß, Inga Nehlmeier, Anika Hartleib, Anna-Sophie Moldenhauer, Sebastian Konzok, Susann Dehmel, Katherina Sewald, Constantin Brinkmann, Christoph Curths, Sascha Knauf, Jens Gruber, Kerstin Mätz-Rensing, Franziska Dahlmann, Armin Braun, Stefan Pöhlmann
The cellular serine protease TMPRSS2, a member of the type II transmembrane serine protease (TTSP) family, cleaves and activates the hemagglutinin of influenza A viruses (FLUAV) in cell culture and is essential for spread of diverse FLUAV in mice. Non-human primates (NHP), in particular rhesus and cynomolgus macaques, serve as animal models for influenza and experimental FLUAV infection of common marmosets has recently also been reported. However, it is currently unknown whether the NHP orthologues of human TMPRSS2 cleave and activate FLUAV hemagglutinin and contribute to viral spread in respiratory tissue...
2017: PloS One
https://www.readbyqxmd.com/read/28488364/comparison-of-the-vaginal-environment-in-rhesus-and-cynomolgus-macaques-pre-and-post-lactobacillus-colonization
#13
Gregory J Daggett, Chunxia Zhao, Fawn Connor-Stroud, Patricia Oviedo-Moreno, Hojin Moon, Michael W Cho, Thomas Moench, Deborah J Anderson, Francois Villinger
BACKGROUND: Rhesus and cynomologus macaques are valuable animal models for the study of human immunodeficiency virus (HIV) prevention strategies. However, for such studies focused on the vaginal route of infection, differences in vaginal environment may have deterministic impact on the outcome of such prevention, providing the rationale for this study. METHODS: We tested the vaginal environment of rhesus and cynomolgus macaques longitudinally to characterize the normal microflora based on Nugent scores and pH...
May 9, 2017: Journal of Medical Primatology
https://www.readbyqxmd.com/read/28487309/molecular-cloning-and-characterization-of-marmoset-aldehyde-oxidase
#14
Shotaro Uehara, Yasuhiro Uno, Eriko Okamoto, Takashi Inoue, Erika Sasaki, Hiroshi Yamazaki
Common marmosets (Callithrix jacchus), New world monkeys, are a promising primate model for preclinical drug metabolism studies due to the similarities of cytochrome P450 (P450) enzyme function to those of humans. Despite an increasing number of drug candidates catalyzed by non-P450 enzymes, drug metabolizing enzymes other than P450s have been hardly identified or characterized in marmosets. In this study, we identified aldehyde oxidase (AOX) 1 gene by marmoset genome analysis. AOX1 cDNA was cloned from marmoset livers by reverse transcription-polymerase chain reaction...
May 9, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28474789/functional-characterization-and-tissue-expression-of-marmoset-cytochrome-p450-2e1
#15
Shotaro Uehara, Yasuhiro Uno, Etsuko Tomioka, Takashi Inoue, Erika Sasaki, Hiroshi Yamazaki
Common marmosets (Callithrix jacchus) have attracted increasing attention as a useful small non-human primate model in preclinical research. However, studies on marmoset cytochrome P450 (P450) 2E enzyme have scarcely been conducted. In this study, the full-length cDNA encoding P450 2E1 enzyme was isolated from marmoset livers by reverse transcription (RT)-polymerase chain reaction (PCR). Marmoset P450 2E1 amino acid sequences were highly identical (>88%) to those of cynomolgus monkey and human P450 2E1 enzymes...
May 5, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28469033/a-highly-potent-extended-half-life-antibody-as-a-potential-rsv-vaccine-surrogate-for-all-infants
#16
Qing Zhu, Jason S McLellan, Nicole L Kallewaard, Nancy D Ulbrandt, Susan Palaszynski, Jing Zhang, Brian Moldt, Anis Khan, Catherine Svabek, Josephine M McAuliffe, Daniel Wrapp, Nita K Patel, Kimberly E Cook, Bettina W M Richter, Patricia C Ryan, Andy Q Yuan, JoAnn A Suzich
Prevention of respiratory syncytial virus (RSV) illness in all infants is a major public health priority. However, no vaccine is currently available to protect this vulnerable population. Palivizumab, the only approved agent for RSV prophylaxis, is limited to high-risk infants, and the cost associated with the requirement for dosing throughout the RSV season makes its use impractical for all infants. We describe the development of a monoclonal antibody as potential RSV prophylaxis for all infants with a single intramuscular dose...
May 3, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28468673/low-potential-for-mechanical-transmission-of-ebola-virus-via-house-flies-musca-domestica
#17
Andrew D Haddow, Farooq Nasar, Christopher W Schellhase, Roger D Moon, Susana L Padilla, Xiankun Zeng, Suzanne E Wollen-Roberts, Joshua D Shamblin, Elizabeth C Grimes, Justine M Zelko, Kenneth J Linthicum, Sina Bavari, M Louise Pitt, John C Trefry
BACKGROUND: Ebola virus (EBOV) infection results in high morbidity and mortality and is primarily transmitted in communities by contact with infectious bodily fluids. While clinical and experimental evidence indicates that EBOV is transmitted via mucosal exposure, the ability of non-biting muscid flies to mechanically transmit EBOV following exposure to the face had not been assessed. RESULTS: To investigate this transmission route, house flies (Musca domestica Linnaeus) were used to deliver an EBOV/blood mixture to the ocular/nasal/oral facial mucosa of four cynomolgus macaques (Macaca fascicularis Raffles)...
May 3, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28467931/activation-of-skeletal-muscle-ampk-promotes-glucose-disposal-and-glucose-lowering-in-non-human-primates-and-mice
#18
Emily C Cokorinos, Jake Delmore, Allan R Reyes, Bina Albuquerque, Rasmus Kjøbsted, Nicolas O Jørgensen, Jean-Luc Tran, Aditi Jatkar, Katherine Cialdea, Ryan M Esquejo, John Meissen, Matthew F Calabrese, Jason Cordes, Robert Moccia, David Tess, Christopher T Salatto, Timothy M Coskran, Alan C Opsahl, Declan Flynn, Matthew Blatnik, Wenlin Li, Erick Kindt, Marc Foretz, Benoit Viollet, Jessica Ward, Ravi G Kurumbail, Amit S Kalgutkar, Jørgen F P Wojtaszewski, Kimberly O Cameron, Russell A Miller
The AMP-activated protein kinase (AMPK) is a potential therapeutic target for metabolic diseases based on its reported actions in the liver and skeletal muscle. We evaluated two distinct direct activators of AMPK: a non-selective activator of all AMPK complexes, PF-739, and an activator selective for AMPK β1-containing complexes, PF-249. In cells and animals, both compounds were effective at activating AMPK in hepatocytes, but only PF-739 was capable of activating AMPK in skeletal muscle. In diabetic mice, PF-739, but not PF-249, caused a rapid lowering of plasma glucose levels that was diminished in the absence of skeletal muscle, but not liver, AMPK heterotrimers and was the result of an increase in systemic glucose disposal with no impact on hepatic glucose production...
May 2, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28462816/in-utero-transfer-of-adeno-associated-viral-vectors-produces-long-term-factor-ix-levels-in-a-cynomolgus-macaque-model
#19
Citra N Z Mattar, Irene Gil-Farina, Cecilia Rosales, Nuryanti Johana, Yvonne Yi Wan Tan, Jenny McIntosh, Christine Kaeppel, Simon N Waddington, Arijit Biswas, Mahesh Choolani, Manfred Schmidt, Amit C Nathwani, Jerry K Y Chan
The safe correction of an inherited bleeding disorder in utero prior to the onset of organ damage is highly desirable. Here, we report long-term transgene expression over more than 6 years without toxicity following a single intrauterine gene transfer (IUGT) at 0.9G using recombinant adeno-associated vector (AAV)-human factor IX (hFIX) in the non-human primate model we have previously described. Four of six treated animals monitored for around 74 months expressed hFIX at therapeutic levels (3.9%-120.0%). Long-term expression was 6-fold higher in males and with AAV8 compared to AAV5, mediated almost completely at this stage by random genome-wide hepatic proviral integrations, with no evidence of hotspots...
April 24, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28462776/a-simple-way-to-eradicate-methicillin-resistant-staphylococcus-aureus-in-cynomolgus-macaques-macaca-fascicularis
#20
Tae M Kim, Hyojun Park, Kyo W Lee, Eun W Choi, Sang H Moon, Yong S Lee, Kahee Cho, Wan J Park, Jae B Park, Sung J Kim
Our investigation of indoor-housed cynomolgus macaques (Macaca fascicularis) by using automated identification followedbyantibiotic susceptibility testing revealed 1 of 7 immunocompetent animals and 2 of 9 immunosuppressed monkeys as carriers ofmethicillin-resistant Staphylococcus aureus (MRSA). Follow-up management involving mupirocin treatment resulted in the conversion of the 3 MRSA carriers into MRSA-negative cases. Prospective assessment of newly imported monkeys involving 24-h culture of nasal swabs on chromogenic agar revealed that 22% (18 of 82 animals) were MRSA-positive...
May 1, 2017: Comparative Medicine
keyword
keyword
75142
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"