Karo Bio AB

Sweden

Karo Bio AB

Sweden
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Nilsson S.,Karo Bio AB | Nilsson S.,Karolinska Institutet | Koehler K.F.,Karo Bio AB | Gustafsson J.-A.,Karo Bio AB | And 2 more authors.
Nature Reviews Drug Discovery | Year: 2011

The two oestrogen receptor subtypes α and β are hormone-regulated modulators of intracellular signalling and gene expression. Regulation of oestrogen receptor activity is crucial not only for development and homeostasis but also for the treatment of various diseases and symptoms. Classical selective oestrogen receptor modulators are well established in the treatment of breast cancer and osteoporosis, but emerging data suggest that the development of subtype-selective ligands that specifically target either oestrogen receptor-α or oestrogen receptor-β could be a more optimal approach for the treatment of cancer, cardiovascular disease, multiple sclerosis and Alzheimer's disease. © 2011 Macmillan Publishers Limited. All rights reserved.


Nilsson S.,Karo Bio AB | Gustafsson J.-A.,Novum | Gustafsson J.-A.,University of Houston
Clinical Pharmacology and Therapeutics | Year: 2011

Over the past two decades, we have learned that estrogens play important physiological roles not only in women but also in men and that the biological effects of estrogen are mediated by not one but two distinct estrogen receptors (ERs), ERα and ERΒ. Our appreciation of the physiological importance of estrogen and the mechanisms by which it acts has significantly increased over the years; however, we are only now beginning to decipher the roles of ERα and ERΒ in different organs and to elucidate how selective ligands, acting through either of the two ERs, can prevent or treat various age- or sex-specific diseases. The specific roles of ERα and ERΒ and the therapeutic potential of ER subtype-selective agonists in bone and metabolic homeostasis, depression, vasomotor symptoms, neurodegenerative diseases, and cancer are reviewed herein. It must be stated, however, that appropriate clinical studies are necessary to validate these compounds as agents for the prevention and treatment of diseases. © 2010 American Society for Clinical Pharmacology and Therapeutics.


Osterlund M.K.,Karo Bio AB
Biochimica et Biophysica Acta - General Subjects | Year: 2010

Background: There is an increased risk for depressive symptoms and affective disorders in individuals who experience drastic drops or fluctuations of gonadal hormones. Moreover, clinical studies indicate that estrogens have the potential to be effective in treating depression. Scope of the review: Possible underlying mechanisms for the antidepressant activity of estrogens are reviewed and discussed. Major conclusions: Estrogens exert their antidepressant activity via a multimodal mechanism of action by regulating several pathways and functions associated with antidepressive effects. Estrogens increase serotonergic activity by regulating the synthesis and degradation of serotonin, as well as spontaneous firing of the serotonergic neurons in the raphe nuclei. Both pre- and postsynaptic serotonin receptors are shown to be regulated by estrogens. In addition, estrogens are neurotrophic and promote neuroplasticity and neurogenesis. Similar effects are also observed after treatment with current antidepressant therapies. However in stark contrast to current therapies which must be administered chronically to produce an effect, the responses to estrogens are often observed after a single dose. Many of these estrogenic effects, including antidepressant and anxiolytic responses in behavioral models in rodents, appear to be mediated via the estrogen receptor β subtype. General significance: The rapid onset of action combined with the multifactorial mechanism of action of estrogens indicates that estrogen treatment could complement currently available therapies for depression. Considering safety aspects, selective estrogen receptor β agonists would probably be the optimal estrogenic therapy. © 2009 Elsevier B.V.


Bonde Y.,Karolinska University Hospital | Breuer O.,Karo Bio AB | Lutjohann D.,University of Bonn | Sjoberg S.,Karolinska University Hospital | And 2 more authors.
Journal of Lipid Research | Year: 2014

Reduced plasma LDL-cholesterol is a hallmark of hyperthyroidism and is caused by transcriptional stimulation of LDL receptors in the liver. Here, we investigated whether thyroid hormone (TH) actions involve other mechanisms that may also account for the reduction in LDL-cholesterol, including effects on proprotein convertase subtilisin/kexin type 9 (PCSK9) and bile acid synthesis. Twenty hyperthyroid patients were studied before and after clinical normalization, and the responses to hyperthyroidism were compared with those in 14 healthy individuals after 14 days of treatment with the liver-selective TH analog eprotirome. Both hyperthyroidism and eprotirome treatment reduced circulating PCSK9, lipoprotein cholesterol, apoB and AI, and lipoprotein(a), while cholesterol synthesis was stable. Hyperthyroidism, but not eprotirome treatment, markedly increased bile acid synthesis and reduced fibroblast growth factor (FGF) 19 and dietary cholesterol absorption. Eprotirome treatment, but not hyperthyroidism, reduced plasma triglycerides. Neither hyperthyroidism nor eprotirome treatment altered insulin, glucose, or FGF21 levels. TH reduces circulating PSCK9, thereby likely contributing to lower plasma LDL-cholesterol in hyperthyroidism. TH also stimulates bile acid synthesis, although this response is not critical for its LDL-lowering effect. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.


Patent
Karo Bio Ab | Date: 2014-01-10

The invention provides a compound of formula (I) wherein G is a pyrazole ring as defined in the specification and R^(4), R^(5), R^(6 )and R^(7 )are as defined in the specification; or a pharmaceutically acceptable ester, amide, solvate or salt thereof, including a salt of such an ester or amide, and a solvate of such an ester, amide or salt. The invention also provides the use of such compounds in the treatment or prophylaxis of a condition associated with a disease or disorder associated with estrogen receptor activity.


Patent
Karo Bio Ab and Bristol Myers Squibb | Date: 2011-09-28

The invention relates to a novel crystalline form of 3-[[3,5-dibromo-4-[4-hydroxy-3-(1-methylethyl)-phonoxy]-phenyl]-amino]-3-oxopropanoic acid, said crystalline form being characterised by a powder X-ray diffraction pattern having major peaks at 2 = 9.00.2, 14.70.2, 19.60.2, 21.60.2, and 24.30.2.


Patent
Karo Bio Ab | Date: 2010-10-06

The invention provides a compound of formula (I) wherein G is a pyrazole ring as defined in the specification and R^(4), R^(5), R^(6 )and R^(7 )are as defined in the specification; or a pharmaceutically acceptable ester, amide, solvate or salt thereof, including a salt of such an ester or amide, and a solvate of such an ester, amide or salt. The invention also provides the use of such compounds in the treatment or prophylaxis of a condition associated with a disease or disorder associated with estrogen receptor activity.


Patent
Karo Bio Ab | Date: 2010-10-06

The invention provides a compound of formula (I) or a pharmaceutically acceptable ester, amide, solvate or salt thereof, including a salt of such an ester or amide, and a solvate of such an ester, amide or salt. The invention also provides the use of such compounds in the treatment or prophylaxis of a condition associated with a disease or disorder associated with estrogen receptor activity. Formula (I) wherein R^(1), R^(2), R^(3), R^(4), R^(5), R^(6), R^(7), R^(8), R^(9 )and R^(10 )are as defined in the specification.


Patent
Karo Bio Ab | Date: 2013-01-11

The invention provides a compound of formula (I) or a pharmaceutically acceptable ester, amide, carbamate, solvate or salt thereof, including a salt of such an ester, amide or carbamate, and a solvate of such an ester, amide, carbamate or salt. The invention also provides also provides the use of such compounds in the treatment or prophylaxis of a condition associated with a disease or disorder associated with estrogen receptor activity, wherein R^(1), R^(2), R^(3), R^(5 )and R^(6 )are as defined in the specification.


Patent
Karo Bio Ab | Date: 2012-08-02

Compounds of formula (I) or a pharmaceutically acceptable ester, amide, carbamate or salt thereof, including a salt of such an ester, amide or carbamate in which R^(1 )to R^(9 )have meanings as defined in the Specification, are useful as estrogen receptor ligands.

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