A5021136090- Peptidase Inhibition and Analysis
- Nitric Oxide and Endothelin Effects
- Eicosanoids and Hypertension Pharmacology
- Cancer, Stress, Anesthesia, and Immune Response
- Prostate Cancer Treatment and Research
- Neuropeptides and Animal Physiology
- CAR-T cell therapy research
- Adenosine and Purinergic Signaling
- Neuroscience of respiration and sleep
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Pulmonary Hypertension Research and Treatments
- Electron Spin Resonance Studies
- Pain Mechanisms and Treatments
- Bone health and treatments
- Cancer Research and Treatments
- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- Psoriasis: Treatment and Pathogenesis
- Cardiac Ischemia and Reperfusion
- Reproductive System and Pregnancy
- Organ and Tissue Transplantation Research
- Autoimmune Bullous Skin Diseases
- Organic Chemistry Cycloaddition Reactions
- Genetics and Neurodevelopmental Disorders
Kymab (United Kingdom)
2019
GlaxoSmithKline (United Kingdom)
2001
University of Hertfordshire
1997-2000
King's College London
1993-1995
University of London
1993-1995
Universidad de Londres
1993-1994
National Hospital for Neurology and Neurosurgery
1994
University College London
1994
7‐Nitro indazole (7‐NI) produces potent inhibition of rat cerebellar nitric oxide synthase (NOS) with an IC 50 0.9 ± 0.1 μ m ( n = 6). NOS activity is dependent on the presence both exogenous CaCl 2 and NADPH. The inhibitory potency 7‐NI remained unaltered in different concentrations either (0.75–7.5 ) or NADPH (0.05–5.0 ). Kinetic (Lineweaver‐Burke) analysis effect revealed that was a competitive nature K i value 5.6 . respect to L‐arginine 2.5 following derivatives (IC values shown...
The functional consequences of P2X receptor activation on peripheral sensory neurones have been investigated in vivo . Behavioural indices acute nociception were monitored the conscious rat following subplantar injection adenosine 5′‐triphosphate (ATP), α,β‐methylene ATP, 5′‐diphosphate (ADP) and adenosine. Signs overt nociception, i.e. hindpaw lifting licking, apparent animals injected with agonist, ATP. Nociceptive behaviours continued for 15 min administration ATP (200 nmol) dose‐related...
7-Nitro indazole (7-NI) inhibits rat striatal, cerebellar, hippocampal, cerebral cortex and olfactory bulb nitric oxide synthase (NOS) in vitro with IC50 values of 0.68 +/- 0.01 microM, 0.64 0.03 1.53 0.05 0.93 0.04 microM 1.05 0.02 respectively (n = 6). Intraperitoneal (i.p.) or oral administration 7-NI (30 mg kg-1) to rats inhibited NOS enzyme activity measured ex vivo all five brain regions 5-6). inhibition (maximal effect, 0.5 h post-injection) was transient complete recovery at either 4...
Abstract Purpose: CD137 is a T- and NK-cell costimulatory receptor involved in consolidating immunologic responses. The potent agonist urelumab has shown clinical promise as cancer immunotherapeutic but development been hampered by on-target off-tumor toxicities. A targeted to the prostate-specific membrane antigen (PSMA), frequently highly expressed on castration-resistant metastatic prostate (mCRPC) tumor cells, could bring effective immunotherapy this immunologically challenging address...
Abstract Background:CB307 is a tri-specific variable heavy-chain antibody fragment against PSMA, CD137, and human serum albumin. It designed to mitigate hepatotoxicity by activating T cells only in the PSMA-positive tumors increase drug half-life albumin binding. This Phase I study investigated safety tolerability of CB307 as monotherapy or with pembrolizumab.Methods: Patients who were heavily pretreated solid enrolled dose-escalation phase monotherapy. Additional efficacy assessed expansion...
Abstract Pulmonary arterial hypertension (PAH) is a rare but fatal disease. Current treatments increase life expectancy have limited impact on the progressive pulmonary vascular remodelling that drives PAH. Osteoprotegerin (OPG) increased within serum and lesions of patients with idiopathic PAH mitogen migratory stimulus for artery smooth muscle cells (PASMCs). Here, we report pro-proliferative phenotype in PASMCs stimulated OPG mediated via Fas receptor treatment human antibody targeting...
. After a period of myocardial ischaemia, reperfusion the myocardium can elicit cardiac arrhythmias. Susceptibility to these arrhythmias declines with time, such that preceding more than approximately 40 min ischaemia is associated few reperfusion‐induced We have tested hypothesis this decline in susceptibility occurs, part, because protection by endogenous guanosine 3′:5′‐cyclic monophosphate (cyclic GMP). Rat isolated hearts were subjected 60 left regional followed ( n = 10 per group)....
The effect of the nitric oxide synthase (NOS) inhibitor, 7‐nitro indazole (7‐NI), on sympathetic and purinergic neurotransmission in rat isolated vas deferens preparation has been studied. 7‐NI (50–200 μ m ) caused a dose‐ frequency‐dependent inhibition phasic (predominantly purinergic) contractile response to electrical (field) stimulation (100 V, 0.5 ms). Greatest occurred at lower frequencies (0.1–10 Hz). sustained tonic noradrenergic) was inhibited only high frequency (60 Hz) highest...
Interleukin (IL)-17A underlies the pathogenesis of chronic plaque psoriasis (CPP). Well-tolerated, effective IL-17A inhibitors for mild-to-moderate CPP are needed. ZL-1102 is a novel antibody fragment targeting IL-17A. To assess safety, tolerability, preliminary efficacy and skin penetration topical 1% hydrogel in patients with CPP, two-part, Phase Ib study was conducted. Open-label Part A: six received single application onto psoriatic plaque; double-blind B: 53 were randomised 1:1 to...
Abstract INTRODUCTION: CD137 is a TNF receptor superfamily (TNFRSF9) costimulatory expressed by T cells and NK cells. Clustering-mediated signaling enhances immune cell survival, proliferation, cytokine production memory formation. CD40 (previously TNFRSF5) related member primarily on B antigen-presenting (APCs) which upon clustering also key modulator of responses. Mesothelin (MSLN) highly upregulated tumor in ovarian pancreatic cancer select other solid tumour histologies. To avoid...
Abstract INTRODUCTION: CD137 is a T and NK cell costimulatory receptor involved in consolidating immunological responses. The potent agonist urelumab has shown clinical promise as cancer immunotherapeutic but development been hampered by on-target off-tumour toxicities. A targeted to the prostate-specific membrane antigen (PSMA), frequently highly expressed on castration-resistant metastatic prostate (mCRPC) tumour cells, could bring effective immunotherapy this immunologically challenging...
<p>Supplementary Figure 8: Spheroid end-of-study T=240h images</p>
<p>Supplementary Figure 9: Neuroendocrine Differentiation Phenotypes in Prostate Cancer Liver Metastases</p>
<p>Supplementary Figure 10: hPSMA expression on RP1 tumour cells is lost over time, even in tumours dosed with HSA only</p>
<p>Supplementary Figure 9: Neuroendocrine Differentiation Phenotypes in Prostate Cancer Liver Metastases</p>
<div>AbstractPurpose:<p>CD137 is a T- and NK-cell costimulatory receptor involved in consolidating immunologic responses. The potent CD137 agonist urelumab has shown clinical promise as cancer immunotherapeutic but development been hampered by on-target off-tumor toxicities. A targeted to the prostate-specific membrane antigen (PSMA), frequently highly expressed on castration-resistant metastatic prostate (mCRPC) tumor cells, could bring effective immunotherapy this...
<p>Supplemental Methods</p>
<p>Supplementary Figure 3: PK/TK dosing strategies</p>
<p>Supplementary Figure 8: Spheroid end-of-study T=240h images</p>