A5085172744- Prostate Cancer Treatment and Research
- Estrogen and related hormone effects
- Protein Degradation and Inhibitors
- Hormonal Regulation and Hypertension
- Histone Deacetylase Inhibitors Research
- Hormonal and reproductive studies
- Cancer, Lipids, and Metabolism
- Cancer-related gene regulation
- Ubiquitin and proteasome pathways
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer, Hypoxia, and Metabolism
- Virus-based gene therapy research
- Eicosanoids and Hypertension Pharmacology
- Vitamin D Research Studies
- Neuroblastoma Research and Treatments
- Cancer Treatment and Pharmacology
- Monoclonal and Polyclonal Antibodies Research
- Pharmaceutical studies and practices
- Cancer, Stress, Anesthesia, and Immune Response
- Peptidase Inhibition and Analysis
- Sexual Differentiation and Disorders
- Cell Adhesion Molecules Research
- Social and Educational Sciences
- Insect Resistance and Genetics
- Collagen: Extraction and Characterization
Orion Corporation (Finland)
2015-2022
Orion Corporation (United Kingdom)
2014
University of Jyväskylä
2000-2006
Abstract Activation of androgen receptor (AR) is crucial for prostate cancer growth. Remarkably, also castration-resistant (CRPC) dependent on functional AR and several mechanisms have been proposed to explain the addiction. Known causes CRPC include gene amplification overexpression as well point mutations AR. We report here pharmacological profile ODM-201, a novel inhibitor that showed significant antitumor activity favorable safety in phase 1/2 studies men with CRPC. ODM-201 full...
The collagens are recognized by the αI domains of collagen receptor integrins. A common structural feature in collagen-binding is presence an extra helix, named helix αC. However, its participation binding has not been shown. Here, we have deleted αC α<sub>2</sub>I domain and tested function resultant recombinant protein (ΔαCα<sub>2</sub>I) using a real-time biosensor. ΔαCα<sub>2</sub>I had reduced affinity for type I (430 ± 90 nm) when compared with wild-type (90 30 nm), indicating both...
Abstract Binding of steroid hormones to their cognate receptors regulates the growth most prostate and breast cancers. We hypothesized that CYP11A inhibition might halt synthesis all hormones, because is only enzyme catalyses first step hormone biosynthesis. speculated a inhibitor could be administered safely provided steroids essential for life are replaced. Virtual screening systematic structure–activity relationship optimization were used develop ODM-208, first-in-class, selective,...
We report the discovery of a novel nonsteroidal dual-action compound, ODM-204, that holds promise for treating patients with castration-resistant prostate cancer (CRPC), an advanced form characterised by high androgen receptor (AR) expression and persistent activation AR signaling axis residual tissue androgens. For has dual mechanism action. The compound is anticipated to efficiently dampen androgenic stimuli in body inhibiting CYP17A1, prerequisite enzyme formation dihydrotestosterone...
The use of baculovirus vectors shows promise as a tool for gene delivery into mammalian cells. These insect viruses have been shown to transduce variety cell lines, and transfer has also demonstrated in vivo. In this study, we generated two recombinant displaying an integrin-specific motif, RKK, part different loops the green fluorescent protein (GFP) fused with major envelope gp64 Autographa californica M nucleopolyhedrovirus. By enzyme linked immunosorbent assays, these were bind peptide...
Abstract Introduction: BET (bromodomain and extraterminal) family proteins (BRD2, BRD3, BRD4, BRDT) are epigenetic readers that bind to acetylated-lysine residues in histones recruit protein complexes promote transcription elongation. In many cancers, have been shown regulate expression of MYC other oncogenic drivers important for cell proliferation survival. Pharmacologic inhibition the BET-histone interaction has result transcriptional downregulation a number oncogenes tumor growth...
5057 Background: Activating AR mutations ensure a continued activation by non-androgen steroid ligands, e.g. progesterone and glucocorticoids. CYP11A1 is the only enzyme that catalyzes conversion of cholesterol to pregnenolone, from which all hormones (glucocorticoids, mineralocorticoids, sex steroids) are subsequently derived. ODM-208, an oral, selective inhibitor CYP11A1, being evaluated for safety efficacy as treatment mCRPC in ongoing CYPIDES phase I/II trial men previously treated with...
340 Background: Castration-resistant prostate cancer (CRPC) is a major cause of mortality worldwide. The mechanisms behind the development resistance are complex and not fully understood; altered androgen synthesis, receptor (AR) overexpression or gene amplification, mutations have been indentified. However, tumor growth may still be responsive to therapies that can further suppress de novo intratumoral steroid synthesis upstream CYP17A1. ODM-208 an oral, non-steroidal selective inhibitor...
Background: Prostate cancer is a major global challenge due to the increasing number of aging population and frequency diagnosis. During past decade new treatments have been targeted androgen signaling axis either by inhibiting binding androgens receptor (AR) AR nuclear translocation, or production via CYP17A1 enzyme. Despite significant progress on research therapies, CRPC still incurable there urgent need for better, more effective treatments. ODM-208 an oral, non-steroidal selective...
Abstract Introduction: The bromodomain and extraterminal (BET) family of proteins are chromatin readers that promote the transcription several important cell identity genes. BET also control expression many genes play an essential role in pathogenesis human cancer, including cell-cycle proliferation-regulating small-molecule inhibitors block binding to have shown antitumor activity a variety pre-clinical cancer models. In this study, we evaluated anticancer novel inhibitor, ODM-207, ER+...
Abstract Background: The Bromodomain (BRD) and Extra-Terminal domain (BET) family of proteins are key regulators epigenetic control. Although pan BET Inhibitors show good clinical activity, progressive disease was seen after several months treatment in responders, likely due to secondary resistance mechanisms. plausible mechanisms increased expression TCF7L2, c-Myc, Survivin PIM1. Cyclic AMP response element binding protein (CREB)-binding (CBP) E1A interacting 300 kDa (EP300 or p300) two...
221 Background: Castration-resistant prostate cancer (CRPC) is characterized by high androgen receptor (AR) expression and persistent activation of AR signaling axis residual tissue/tumor androgens. Targeting biosynthesis together may be more effective than either alone. ODM-204 a novel, non-steroidal dual inhibitor CYP17A1 AR, which has shown promising results in preclinical studies. Methods: The binding affinity to wild type was determined rat cytosolic lysates. potency functional activity...
Abstract Background: Bromodomain and extra-terminal (BET) family proteins are dual bromodomain-containing epigenetic readers that bind to acetylated-lysine residues at gene promoter enhancer elements in histones recruit protein complexes promote transcriptional elongation. Recent evidence demonstrates BET bromodomain inhibition leads anti-proliferative activity pre-clinical models of many hematological malignancies solid tumors. Selective bromodomains by small molecule inhibitors has emerged...
Abstract Introduction: The bromodomain and extraterminal (BET) family of proteins are chromatin readers that recognize bind to specific acetylated histones promote the transcription several important cell identity genes. BET inhibitors have shown promising antitumor activity in a variety pre-clinical cancer models, as inhibition abrogates key oncogenes type-specific manner. It is known effectively inhibits proliferation estrogen receptor positive (ER+) breast cells, at least part through...
Introduction: The bromodomain and extraterminal (BET) family of proteins are chromatin readers that promote the transcription several important cell identity genes. BET also control expression many genes play an essential role in pathogenesis human cancer, including cell-cycle proliferation-regulating small-molecule inhibitors block binding to have shown antitumor activity a variety pre-clinical cancer models. In this study, we evaluated anticancer novel inhibitor, ODM-207, ER+ breast models...
Abstract Androgen receptor (AR) mutations have been described to emerge in response prostate cancer treatment with first generation AR antagonists, resulting broadened ligand specificity and antagonist-to-agonist switch. Second-generation antagonists enzalutamide ARN-509 function as the presence of overexpression. They express high clinical efficacy castration resistant (CRPC) but eventually resistance will emerge. Recently, a F876L missense mutation ligand-binding domain has that confers...
230 Background: Castration-resistant prostate cancer (CRPC) is characterized by high androgen receptor (AR) expression and persistent activation of AR signaling axis residual tissue androgens. Inhibiting biosynthesis together may be more effective than inhibiting either alone to treat CRPC. ODM-204 a potent, orally administered investigational non-steroidal dual inhibitor CYP17A1 AR. In vivo, shows favourable pharmacokinetic/ pharmacodynamics (PK/PD) properties in intact mature male monkeys...
Supplementary Data from First-in-Class Small Molecule to Inhibit CYP11A1 and Steroid Hormone Biosynthesis
Supplementary Data from First-in-Class Small Molecule to Inhibit CYP11A1 and Steroid Hormone Biosynthesis
<div>Abstract<p>Binding of steroid hormones to their cognate receptors regulates the growth most prostate and breast cancers. We hypothesized that CYP11A inhibition might halt synthesis all hormones, because is only enzyme catalyses first step hormone biosynthesis. speculated a inhibitor could be administered safely provided steroids essential for life are replaced. Virtual screening systematic structure–activity relationship optimization were used develop ODM-208,...
<div>Abstract<p>Binding of steroid hormones to their cognate receptors regulates the growth most prostate and breast cancers. We hypothesized that CYP11A inhibition might halt synthesis all hormones, because is only enzyme catalyses first step hormone biosynthesis. speculated a inhibitor could be administered safely provided steroids essential for life are replaced. Virtual screening systematic structure–activity relationship optimization were used develop ODM-208,...