A5080207443- Estrogen and related hormone effects
- Psoriasis: Treatment and Pathogenesis
- Neuroendocrine regulation and behavior
- Receptor Mechanisms and Signaling
- Aquaculture Nutrition and Growth
- Pharmacogenetics and Drug Metabolism
- Inflammatory mediators and NSAID effects
- Chemical synthesis and alkaloids
- Hormonal and reproductive studies
- Reproductive biology and impacts on aquatic species
- Carbohydrate Chemistry and Synthesis
- Cytokine Signaling Pathways and Interactions
- Stress Responses and Cortisol
- Neuropeptides and Animal Physiology
- Asthma and respiratory diseases
- Fungal Biology and Applications
- Dermatology and Skin Diseases
- Hypothalamic control of reproductive hormones
- Diet and metabolism studies
- T-cell and B-cell Immunology
- Organophosphorus compounds synthesis
- Synthetic Organic Chemistry Methods
- Olfactory and Sensory Function Studies
- Cancer Treatment and Pharmacology
- Analytical Chemistry and Chromatography
AstraZeneca (Sweden)
1992-2025
Medicines for Malaria Venture
2022
AstraZeneca (United Kingdom)
2014
Uppsala University
1997
Graco (United States)
1996
Lund University
1987-1991
Karolinska Institutet
1984-1990
Integrated Cardio Metabolic Centre
1984-1989
University of Gothenburg
1982
Abstract RORγt, an isoform of the retinoic acid‐related orphan receptor gamma (RORc, RORγ), has been identified as master regulator T‐helper 17 (T H 17) cell function and development, making it attractive target for treatment autoimmune diseases. Validation this comes from antibodies targeting interleukin‐17 (IL‐17), signature cytokine produced by T cells, which have shown impressive results in clinical trials. Through focused screening our compound collection, we a series N‐ sulfonylated...
A class of potent, nonsteroidal, selective indazole ether-based glucocorticoid receptor modulators (SGRMs) was developed for the inhaled treatment respiratory diseases. Starting from an orally available compound with demonstrated anti-inflammatory activity in rat, a soft-drug strategy implemented to ensure rapid elimination drug candidates minimize systemic GR activation. The first clinical candidate 1b (AZD5423) displayed potent inhibition lung edema rat model allergic airway inflammation...
Multiple genetic associations suggest a causative relationship between Th17-related genes coding for proteins, such as IL-17A, IL-23 and STAT3, psoriasis. Further support this link comes from the findings that neutralizing antibodies directed against IL-17RA are efficacious in diseases like psoriasis, psoriatic arthritis ankylosing spondylitis. RORγt is centrally positioned transcription factor driving Th17 polarization cytokine secretion modulation of may thus provide additional benefit to...
The effects of neurotensin in vitro (1–100 n m ) on the binding characteristics [ 3 H]N‐propylnorapomorphine ([ H]NPA) were analysed striatal membrane preparations adult male rat. Subsequently, it was investigated whether modulatory To nmt H]NPA altered by treatment with toluene vivo (80 p.p.m., days, 6 h day ‐1 and (19 μ mol ml ). Displacement raclopride (IC 50 about 15 SCH 23390 (without effect) indicated that labelled only D 2 dopamine receptors present study. Neurotensin found to reduce...
Retinoic acid receptor related orphan γt (RORγt), has been identified as the master regulator of TH17-cell function and development, making it an attractive target for treatment autoimmune diseases by a small-molecule approach. Herein, we describe our investigations on series 4-aryl-thienyl acetamides, which were guided insights from X-ray cocrystal structures. Efforts in targeting cofactor-recruitment site 4-aryl group thiophene led to potent binders with nanomolar activity primary...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA short enantiospecific route to isodaucane sesquiterpenes from limonene. On the absolute configuration of (+)-aphanamol I and II.Thomas Hansson Boerje WickbergCite this: J. Org. Chem. 1992, 57, 20, 5370–5376Publication Date (Print):September 1, 1992Publication History Published online1 May 2002Published inissue 1 September 1992https://pubs.acs.org/doi/10.1021/jo00046a018https://doi.org/10.1021/jo00046a018research-articleACS PublicationsRequest...
A quantitative assessment of the levels cytochromes P-450 b and c in brains pituitary glands untreated beta-naphthoflavone (BNF)-pretreated rats was made with polyclonal antibodies raised against hepatic sensitive fluorometric assay catalytic activity, namely, O-deethylation ethoxycoumarin (ETC). In microsomal fraction rats, rate formation 7-hydroxycoumarin from ETC ranged between 0.1 20 pmol/min/mg protein, which is approximately 0.01-2% level microsomes phenobarbital-induced rats. This...
ABSTRACT Sexual behaviour was induced in castrated male rats with oestradiol-17β- or testosterone-filled constant-release implants. Testosterone-induced sexual unaffected by treatment the 5α-reductase inhibitor 17β-N,N-diethylcarbamoyl-4-aza-5α-androstan-3-one (4-MA; 16·7 mg/day) but aromatization 1,4,6-androstatriene-3,17-dione (ATD; 10 prevented testosterone from inducing behaviour. could be activated treated plus ATD 4-MA implants filled a low dose of oestradiol. Lordosis ovariectomized...
Background: Glucocorticoids are the most potent anti-inflammatory drugs available and allow successful treatment of several chronic inflammatory autoimmune diseases. The discovery molecular mechanisms glucocorticoid receptor (GR), recognition that activation repression gene expression could be addressed separately, opened possibility improving safety profiles by identifying ligands predominantly induce over activation. Recent progress in development dissociated other non-steroidal GR...
The further optimization of a recently disclosed series inverse agonists the nuclear receptor RORC2 is described. Investigations into left-hand side compound 1, guided by X-ray crystal structures, led to substitution 4-aryl-thiophenyl residue with hexafluoro-2-phenyl-propan-2-ol moiety. This change resulted in 28, which combined improved drug-like properties good cell potency and significantly lower dose, using an early dose man prediction. Target engagement vivo was demonstrated thymus mice...
Inverse agonists of the nuclear receptor RORC2 have been widely pursued as a potential treatment for variety autoimmune diseases. We discovered novel series isoindoline-based inverse RORC2, derived from our recently disclosed agonist 2. Extensive structure–activity relationship (SAR) studies resulted in AZD0284 (20), which combined potent inhibition IL-17A secretion primary human TH17 cells with excellent metabolic stability and good PK preclinical species. In two vivo studies, compound 20...
Subacute treatment with toluene (80–1500 p.p.m.) produces a dose‐dependent reduction of affinity and increase in density the β‐adrenergic antagonist [ 3 H]dihydroalprenolol binding sites frontoparietal cortex male rat, while characteristics a,‐adrenergic ([ H]WB 4101) α 2 ‐ adrenergic H]p‐aminoclonidine) same region is unaffected by this as evaluated vitro . Therefore, it suggested that cortical receptors are particularly vulnerable to action vivo It speculated result neurotransmission may...
(+)-Isovelleral, an antibiotic and antifeedant sesquiterpene dialdehyde from Basidiomycetes, has been synthesised via a diastereoselective intramolecular Diels–Alder cyclisation of chiral intermediate derived D-ribonolactone.
1. Polyclonal antibodies against rat cytochrome P-450c (IA1), P-450d (IA2), P-450b (IIB1), P-450h (IIC11) and P-450j (IIE1), were used to probe liver microsomes prepared from six sea bird species collected the Irish Sea between 1978 1988.2. Significant cross-reactivity in all was seen only with P450 IA1. Expression of cross-reactive proteins highly variable individual birds, which show evidence environmental induction.3. Shared epitopes IA1 IA2 on a single protein expressed cormorant...
New antimalarial treatments with novel mechanism of action are needed to tackle Plasmodium falciparum infections that resistant first-line therapeutics. Here we report the exploration MMV692140 (2) from Pathogen Box, a collection 400 compounds was made available by Medicines for Malaria Venture (MMV) in 2015. Compound 2 profiled vitro models malaria and found be active against multiple life-cycle stages parasites. The mode resistance, putatively its action, identified as translation...
Effects of subacute toluene exposure (80 p.p.m. in air, 5 + 4 days, 6 h day ‐1 ) were analysed on calcium (Ca 2 +)‐ and cyclic adenosine monophosphate (cAMP)‐induced protein phosphorylation levels membrane preparations from the frontoparietal cortex striatum adult male rat. After separation by gel electrophoresis, amount radioactive phosphate incorporated 5′‐[ γ ‐ 32 P] triphosphate, tetra‐(ethylammonium) salt ([ P]ATP) was measured indirectly auto‐radiography. The 21 most phosphorylated...
ABSTRACT Castrated male rats were treated with constant-release implants filled testosterone, oestradiol-17β, 17β-hydroxy-5α-androstan-3-one (5α-dihydrotestosterone; DHT), 5α-androstane-3α,17β-diol (3α-Adiol) or 5α-androstane-3β,17β-diol (3β-Adiol). Only testosterone activated the sexual behaviour of rats. If combined oestradiol, DHT 3α-Adiol induced behaviour, but 3β-Adiol failed to have this effect. Oestradiol inhibited in-vitro formation [ 14 C]Adiols from C]DHT by preoptic and...