J. Oyarzábal

发表

Overview of the chemical compound and drug name recognition ( CHEMDNER ) task

A. Valencia, F. Leitner, Martin Krallinger, 2013 .

Gael Pérez Rodríguez, Martín Pérez Pérez, A. Valencia, 2015 .

Information Retrieval and Text Mining Technologies for Chemistry.

A. Valencia, Martin Krallinger, A. Lourenço, 2017, Chemical reviews.

Discovery of in Vivo Chemical Probes for Treating Alzheimer's Disease: Dual Phosphodiesterase 5 (PDE5) and Class I Histone Deacetylase Selective Inhibitors.

O. Rabal, J. Oyarzábal, J. Sánchez-Arias, 2018, ACS chemical neuroscience.

Discovery of mitogen-activated protein kinase-interacting kinase 1 inhibitors by a comprehensive fragment-oriented virtual screening approach.

O. Rabal, J. Oyarzábal, Manuel Urbano-Cuadrado, 2010, Journal of medicinal chemistry.

Phosphodiesterases as therapeutic targets for Alzheimer's disease.

R. Franco, J. Oyarzábal, M. Cuadrado-Tejedor, 2012, ACS chemical neuroscience.

A cell-based screen identifies ATR inhibitors with synthetic lethal properties for cancer-associated mutations

James R Bischoff, Julen Oyarzabal, Joaquin Pastor, 2011, Nature Structural &Molecular Biology.

Computational medicinal chemistry in fragment-based drug discovery: what, how and when.

Manuel Urbano-Cuadrado, Obdulia Rabal, Julen Oyarzabal, 2011, Future medicinal chemistry.

Discovery of 1,5-disubstituted pyridones: a new class of positive allosteric modulators of the metabotropic glutamate 2 receptor.

María Lourdes Linares, G. Macdonald, G. Tresadern, 2010, ACS chemical neuroscience.

Identification of LAG3 high affinity aptamers by HT-SELEX and Conserved Motif Accumulation (CMA)

O. Rabal, J. Oyarzábal, J. Lasarte, 2017, PloS one.

In Silico Aptamer Docking Studies: From a Retrospective Validation to a Prospective Case Study'TIM3 Aptamers Binding.

Obdulia Rabal, Julen Oyarzabal, O. Rabal, 2016, Molecular therapy. Nucleic acids.

A simple synthesis of 3-phosphonyl-4-aminoquinolines from β-enaminophosphonates

J. Oyarzábal, F. Palacios, A. O. D. Retana, 1999 .

Omipalisib inspired macrocycles as dual PI3K/mTOR inhibitors.

J. Oyarzábal, C. Blanco-Aparicio, R. Álvarez, 2020, European journal of medicinal chemistry.

Hit to lead evaluation of 1,2,3-triazolo[4,5-b]pyridines as PIM kinase inhibitors.

J. Oyarzábal, J. Fominaya, N. Ajenjo, 2012, Bioorganic & medicinal chemistry letters.

CM352 Reduces Brain Damage and Improves Functional Recovery in a Rat Model of Intracerebral Hemorrhage

J. Oyarzábal, T. Sobrino, F. Campos, 2017, Journal of the American Heart Association.

Discovery and safety profiling of a potent preclinical candidate, (4-[4-[[(3R)-3-(hydroxycarbamoyl)-8-azaspiro[4.5]decan-3-yl]sulfonyl]phenoxy]-N-methylbenzamide) (CM-352), for the prevention and treatment of hemorrhage.

O. Rabal, J. Oyarzábal, J. Paramo, 2015, Journal of medicinal chemistry.

Searching for Peptide Inhibitors of T Regulatory Cell Activity by Targeting Specific Domains of FOXP3 Transcription Factor

J. Oyarzábal, A. Pineda-Lucena, J. Lasarte, 2021, Biomedicines.

Targeting aberrant DNA methylation in mesenchymal stromal cells as a treatment for myeloma bone disease

C. Ortiz de Solórzano, E. Ballestar, F. Prósper, 2019, bioRxiv.

Inhibition of FOXP3/NFAT Interaction Enhances T Cell Function after TCR Stimulation

J. Prieto, J. Oyarzábal, P. Coffer, 2015, The Journal of Immunology.

Repurposing ciclopirox as a pharmacological chaperone in a model of congenital erythropoietic porphyria

P. Dubus, J. Castilla, J. Oyarzábal, 2018, Science Translational Medicine.

Impact of Scaffold Exploration on Novel Dual-Acting Histone Deacetylases and Phosphodiesterase 5 Inhibitors for the Treatment of Alzheimer's Disease.

O. Rabal, J. Oyarzábal, J. Sánchez-Arias, 2017, ACS chemical neuroscience.

Towards the understanding of the activity of G9a inhibitors: an activity landscape and molecular modeling approach

José L. Medina-Franco, Obdulia Rabal, Julen Oyarzabal, 2020, Journal of Computer-Aided Molecular Design.

CM-352 Efficacy in a Mouse Model of Anticoagulant-Associated Intracranial Hemorrhage

J. Oyarzábal, A. Pineda-Lucena, J. Paramo, 2022, Thrombosis and haemostasis.

Phenotypic Screening To Discover Novel Chemical Series as Efficient Antihemorrhagic Agents.

O. Rabal, J. Oyarzábal, Hongyu Ma, 2018, ACS medicinal chemistry letters.

Dual epigenetic modifiers for cancer therapy

F. Prósper, X. Agirre, O. Rabal, 2017, Molecular & cellular oncology.

An easy strategy for the synthesis of 5-phosphorylated pyrimidin-2,4-diones from β-phosphine oxide and phosphonate enamines

J. Oyarzábal, F. Palacios, Jesús M. García, 1999 .

A novel FTY720 analogue targets SET-PP2A interaction and inhibits growth of acute myeloid leukemia cells without inducing cardiac toxicity.

F. Prósper, M. Odero, O. Rabal, 2019, Cancer letters.

StimulationEnhances T Cell Function after TCR Inhibition of FOXP3/NFAT Interaction

J. Oyarzábal, P. Coffer, S. Hervás-Stubbs, 2015 .

Discovery of selective ligands for telomeric RNA G-quadruplexes (TERRA) through 19F-NMR based fragment screening.

Carlos González, A. Villasanté, J. Oyarzábal, 2014, ACS chemical biology.

mRNA-based therapy in a rabbit model of variegate porphyria offers new insights into the pathogenesis of acute attacks

M. Alegre, M. Avila, J. Oyarzábal, 2021, Molecular Therapy. Nucleic Acids.

Pim 1 kinase inhibitor ETP-45299 suppresses cellular proliferation and synergizes with PI3K inhibition.

J. Oyarzábal, J. Leal, J. Bischoff, 2011, Cancer letters.

Trimethylamine-N-Oxide (TMAO) Predicts Cardiovascular Mortality in Peripheral Artery Disease

J. Oyarzábal, J. Paramo, A. Fernández-Montero, 2019, Scientific Reports.

Rapid identification of ETP-46992, orally bioavailable PI3K inhibitor, selective versus mTOR.

M. Barbacid, F. Mulero, P. Pizcueta, 2012, Bioorganic & medicinal chemistry letters.

Identification of ETP-46321, a Potent and Orally Bioavailable PI3K α, δ Inhibitor.

M. Barbacid, F. Mulero, P. Pizcueta, 2012 .

The AhpC and AhpD Antioxidant Defense System of Mycobacterium tuberculosis *

P. Ortiz de Montellano, J. Oyarzábal, A. Wilks, 2000, The Journal of Biological Chemistry.

CHEMDNER: The drugs and chemical names extraction challenge

Alfonso Valencia, Martin Krallinger, Florian Leitner, 2015, Journal of Cheminformatics.

Design, synthesis, and biological evaluation of novel matrix metalloproteinase inhibitors as potent antihemorrhagic agents: from hit identification to an optimized lead.

O. Rabal, J. Oyarzábal, Hongyu Ma, 2015, Journal of medicinal chemistry.

Pharmacokinetic investigation of sildenafil using positron emission tomography and determination of its effect on cerebrospinal fluid cGMP levels

J. Lanciego, R. Franco, J. Oyarzábal, 2016, Journal of neurochemistry.

A “one pot” synthesis of polysubstituted pyridines from metallated alkylphosphonates, nitriles and α,β-unsaturated ketones

J. Oyarzábal, F. Palacios, A. O. D. Retana, 1996 .

Preparation of Fluoroalkyl Imines, Amines, Enamines, Ketones, α-Amino Carbonyls, and α-Amino Acids from Primary Enamine Phosphonates†

J. Oyarzábal, F. Palacios, S. Pascual, 2004 .

Fluoroalkyl alpha,beta-unsaturated imines. Valuable synthetic intermediates from primary fluorinated enamine phosphonates.

J. Oyarzábal, F. Palacios, A. M. Ochoa de Retana, 2002, Organic letters.

Synthesis of novel 2,5-dihydro-1,5,2-diazaphosphinines from primary enamine phosphonates and from alkyl phosphonates

J. Oyarzábal, F. Palacios, J. M. Ezpeleta, 2005 .

A new and efficient strategy for the preparation of 1,5,2-diazaphosphorines from primary β-enaminophosphonates

J. Oyarzábal, F. Palacios, A. O. D. Retana, 1999 .

A simple and efficient strategy for the preparation of 5-phosphorylated imidazol-2-ones from primary β-enaminophosphonates

J. Oyarzábal, F. Palacios, J. M. Ezpeleta, 1998 .

SYNTHESIS OF 5-PHOSPHONYL-2(1H)-PYRIDONES FROM PRIMARY BETA -ENAMINOPHOSPHONATE AND ACETYLENIC ESTERS

J. Oyarzábal, F. Palacios, A. O. D. Retana, 1995 .

Discovery of novel triazolo[4,3-b]pyridazin-3-yl-quinoline derivatives as PIM inhibitors.

O. Rabal, J. Oyarzábal, J. Bischoff, 2019, European journal of medicinal chemistry.

Novel approach for chemotype hopping based on annotated databases of chemically feasible fragments and a prospective case study: new melanin concentrating hormone antagonists.

Julen Oyarzabal, Trevor Howe, I. van der Linden, 2009, Journal of medicinal chemistry.

Design, Synthesis, and Biological Evaluation of First-in-Class Dual Acting Histone Deacetylases (HDACs) and Phosphodiesterase 5 (PDE5) Inhibitors for the Treatment of Alzheimer's Disease.

O. Rabal, J. Oyarzábal, J. Sánchez-Arias, 2016, Journal of medicinal chemistry.

Mechanism and structure-activity relationships of norspermidine-based peptidic inhibitors of trypanothione reductase.

J. Essex, M. Bradley, J. Oyarzábal, 2005, Bioorganic & medicinal chemistry.

2-Oxaadamant-1-yl ureas as soluble epoxide hydrolase inhibitors: in vivo evaluation in a murine model of acute pancreatitis.

M. Loza, J. Brea, J. Oyarzábal, 2020, Journal of medicinal chemistry.

Two Affinity Sites of the Cannabinoid Subtype 2 Receptor Identified by a Novel Homogeneous Binding Assay

J. Lanciego, R. Franco, O. Rabal, 2016, The Journal of Pharmacology and Experimental Therapeutics.

Binding and Signaling Studies Disclose a Potential Allosteric Site for Cannabidiol in Cannabinoid CB2 Receptors

Julen Oyarzabal, Pier Andrea Borea, Gemma Navarro, 2017, Front. Pharmacol..

Discovery of Reversible DNA Methyltransferase and Lysine Methyltransferase G9a Inhibitors with Antitumoral in Vivo Efficacy.

J. Martinez-Climent, F. Prósper, X. Agirre, 2018, Journal of medicinal chemistry.

Hsp70 protects from stroke in atrial fibrillation patients by preventing thrombosis without increased bleeding risk.

O. Rabal, J. Oyarzábal, J. González-Porras, 2016, Cardiovascular research.

Chemical Interrogation of FOXO3a Nuclear Translocation Identifies Potent and Selective Inhibitors of Phosphoinositide 3-Kinases*

O. Rabal, J. Oyarzábal, J. Bischoff, 2009, The Journal of Biological Chemistry.

Novel pharmacological maps of protein lysine methyltransferases: key for target deorphanization

Obdulia Rabal, Julen Oyarzabal, Andrea Castellar, 2018, Journal of Cheminformatics.

Reversible dual inhibitor against G9a and DNMT1 improves human iPSC derivation enhancing MET and facilitating transcription factor engagement to the genome

F. Prósper, X. Agirre, O. Rabal, 2017, PloS one.

Endogenous retroelement activation by epigenetic therapy reverses the Warburg effect and elicits mitochondrial-mediated cancer cell death.

M. Moreno-Aliaga, Jiahuai Han, J. Martinez-Climent, 2020, Cancer discovery.

An integrated one-step system to extract, analyze and annotate all relevant information from image-based cell screening of chemical libraries.

Obdulia Rabal, Wolfgang Link, Beatriz G Serelde, 2010, Molecular bioSystems.

Inhibition of a G9a/DNMT network triggers immune-mediated bladder cancer regression

F. Prósper, G. De Velasco, X. Agirre, 2019, Nature Medicine.

Imidazo[1,2-a]pyrazines as novel PI3K inhibitors.

O. Rabal, J. Oyarzábal, J. Bischoff, 2012, Bioorganic & medicinal chemistry letters.

GPR55: A therapeutic target for Parkinson's disease?

C. Müller, R. Franco, J. Oyarzábal, 2017, Neuropharmacology.

The CHEMDNER corpus of chemicals and drugs and its annotation principles

Zhiyong Lu, Karin M. Verspoor, Hongfang Liu, 2015, Journal of Cheminformatics.

Using Novel Descriptor Accounting for Ligand-Receptor Interactions To Define and Visually Explore Biologically Relevant Chemical Space

Obdulia Rabal, Julen Oyarzabal, O. Rabal, 2012, J. Chem. Inf. Model..

Targeting the anion exchanger 2 with specific peptides as a new therapeutic approach in B lymphoid neoplasms

J. Martinez-Climent, J. Prieto, O. Rabal, 2017, Haematologica.

A First-in-Class Small-Molecule that Acts as a Dual Inhibitor of HDAC and PDE5 and that Rescues Hippocampal Synaptic Impairment in Alzheimer’s Disease Mice

G. Perea, R. Franco, O. Rabal, 2017, Neuropsychopharmacology.

Decreased levels of guanosine 3′, 5′‐monophosphate (cGMP) in cerebrospinal fluid (CSF) are associated with cognitive decline and amyloid pathology in Alzheimer's disease

R. Franco, J. Oyarzábal, A. Cedazo-Mínguez, 2015, Neuropathology and applied neurobiology.

In vivo, in vitro and in silico methods for small molecule transfer across the BBB.

Julen Oyarzabal, Patrick Augustijns, Claire Mackie, 2009, Journal of pharmaceutical sciences.

Discovery of first-in-class reversible dual small molecule inhibitors against G9a and DNMTs in hematological malignancies

J. Martinez-Climent, F. Prósper, J. Martín-Subero, 2017, Nature Communications.

Dual Targeting of Histone Methyltransferase G9a and DNA‐Methyltransferase 1 for the Treatment of Experimental Hepatocellular Carcinoma

R. Urtasun, F. Prósper, J. Zucman‐Rossi, 2019, Hepatology.

Epigenetic drugs in Alzheimer’s disease

R. Franco, J. Oyarzábal, A. García-Osta, 2013, Biomolecular concepts.

Salermide, a Sirtuin inhibitor with a strong cancer-specific proapoptotic effect

M. Fraga, S. Ropero, M. Esteller, 2009, Oncogene.

ICAM‐1 Peptide Inhibitors of T‐cell Adhesion bind to the allosteric site of LFA‐1. An NMR Characterization

J. Oyarzábal, B. A. Tejo, T. Siahaan, 2007, Chemical biology & drug design.

Blockage of FOXP3 transcription factor dimerization and FOXP3/AML1 interaction inhibits T regulatory cell activity: sequence optimization of a peptide inhibitor

J. Prieto, O. Rabal, J. Oyarzábal, 2017, Oncotarget.

Zebrafish: Speeding Up the Cancer Drug Discovery Process.

Julen Oyarzabal, J. Oyarzábal, I. de Miguel, 2018, Cancer research.

Targeting CB1 and GPR55 Endocannabinoid Receptors as a Potential Neuroprotective Approach for Parkinson’s Disease

J. Lanciego, R. Franco, J. Oyarzábal, 2019, Molecular neurobiology.

Fatty acid amide hydrolase inhibition for the symptomatic relief of Parkinson’s disease

R. Franco, J. Oyarzábal, R. Maldonado, 2016, Brain, Behavior, and Immunity.

Impact of Neurodegenerative Diseases on Drug Binding to Brain Tissues: From Animal Models to Human Samples

J. Oyarzábal, A. Ugarte, A. García-Osta, 2018, Neurotherapeutics.

Tadalafil crosses the blood–brain barrier and reverses cognitive dysfunction in a mouse model of AD

J. Lanciego, R. Franco, J. Oyarzábal, 2013, Neuropharmacology.

The monoacylglycerol lipase inhibitor JZL184 is neuroprotective and alters glial cell phenotype in the chronic MPTP mouse model

R. Franco, J. Oyarzábal, C. Hillard, 2014, Neurobiology of Aging.

Dual Targeting of G9a and DNA Methyltransferase‐1 for the Treatment of Experimental Cholangiocarcinoma

C. Trautwein, F. Prósper, S. Morini, 2020, Hepatology.

Targeting CB1 and GPR55 Endocannabinoid Receptors as a Potential Neuroprotective Approach for Parkinson’s Disease

J. Lanciego, J. Oyarzábal, Gemma Navarro, 2019, Molecular Neurobiology.

Decreased levels of cGMP in CSF are associated with cognitive decline and amyloid pathology in Alzheimer ’ s disease 1 Authors :

R. Franco, J. Oyarzábal, A. Cedazo-Mínguez, 2014 .

Phosphodiesterase inhibition in cognitive decline.

J. Lanciego, R. Franco, J. Oyarzábal, 2014, Journal of Alzheimer's disease : JAD.

Evaluation of chemical and gene/protein entity recognition systems at BioCreative V.5: the CEMP and GPRO patents tracks

Alfonso Valencia, Martín Pérez-Pérez, Anália Lourenço, 2017 .

Optimizing the Performance of In Silico ADMET General Models According to Local Requirements: MARS Approach. Solubility Estimations As Case Study

Julen Oyarzabal, Joaquin Pastor, Trevor J. Howe, 2009, J. Chem. Inf. Model..

Epigenetic mechanisms and metabolic reprogramming in fibrogenesis: dual targeting of G9a and DNMT1 for the inhibition of liver fibrosis

F. Prósper, B. Sangro, J. Oyarzábal, 2020, Gut.

Inducing heat shock protein 70 expression provides a robust anti-thrombotic effect with minimal bleeding risk

J. Oyarzábal, E. Guruceaga, R. Lecumberri, 2017, Thrombosis and Haemostasis.

Dual Pharmacological Targeting of HDACs and PDE5 Inhibits Liver Disease Progression in a Mouse Model of Biliary Inflammation and Fibrosis

B. Sangro, J. Oyarzábal, M. Ávila, 2020, Cancers.

Development and Validation of Molecular Overlays Derived from Three-Dimensional Hydrophobic Similarity with PharmScreen

F. J. Luque, Enric Herrero, Enric Gibert, 2018, J. Chem. Inf. Model..

Defining the mechanism of action of 4-phenylbutyrate to develop a small-molecule-based therapy for Alzheimer's disease.

R. Franco, J. Oyarzábal, A. García-Osta, 2011, Current medicinal chemistry.

Targeting aberrant DNA methylation in mesenchymal stromal cells as a treatment for myeloma bone disease

E. Ballestar, M. Esteller, F. Prósper, 2021, Nature Communications.

Design, synthesis, biological evaluation and in vivo testing of dual phosphodiesterase 5 (PDE5) and histone deacetylase 6 (HDAC6)-selective inhibitors for the treatment of Alzheimer's disease.

O. Rabal, J. Oyarzábal, J. Sánchez-Arias, 2018, European journal of medicinal chemistry.

Concomitant histone deacetylase and phosphodiesterase 5 inhibition synergistically prevents the disruption in synaptic plasticity and it reverses cognitive impairment in a mouse model of Alzheimer’s disease

G. Perea, R. Franco, O. Rabal, 2015, Clinical Epigenetics.

LimTox: a web tool for applied text mining of adverse event and toxicity associations of compounds, drugs and genes

Martin Krallinger, Salvador Capella-Gutiérrez, Obdulia Rabal, 2017, Nucleic Acids Res..

Databases of protein-protein interactions and their use in drug discovery.

Julen Oyarzabal, Ana M Rojas, Gloria Fuentes, 2009, Current opinion in drug discovery & development.

Overview of the BioCreative VI chemical-protein interaction Track

Anália Lourenço, Martin Krallinger, Obdulia Rabal, 2017 .

Multitarget Approach for the Treatment of Alzheimer`s Disease: Inhibition of Phosphodiesterase 9 (PDE9) and Histone Deacetylases (HDACs) covering diverse selectivity profiles.

O. Rabal, J. Oyarzábal, A. Pineda-Lucena, 2019, ACS chemical neuroscience.

Taking Advantage of the Selectivity of Histone Deacetylases and Phosphodiesterase Inhibitors to Design Better Therapeutic Strategies to Treat Alzheimer’s Disease

O. Rabal, J. Oyarzábal, V. Segura, 2019, Front. Aging Neurosci..

Biologically Relevant Chemical Space Navigator: From Patent and Structure-Activity Relationship Analysis to Library Acquisition and Design

Obdulia Rabal, Julen Oyarzabal, O. Rabal, 2012, J. Chem. Inf. Model..

Systematic Roadmap for Cancer Drug Screening Using Zebrafish Embryo Xenograft Cancer Models: Melanoma Cell Line as a Case Study

J. Oyarzábal, A. Hurlstone, María Montoya, 2021, Cancers.

Fragment-Hopping-Based Discovery of a Novel Chemical Series of Proto-Oncogene PIM-1 Kinase Inhibitors

Obdulia Rabal, Julen Oyarzabal, Joaquin Pastor, 2012, PloS one.

Salermide, a Sirtuin inhibitor with a strong cancer-specific proapoptotic effect

M. Fraga, S. Ropero, M. Esteller, 2009, Oncogene.

Conformational selection versus induced fit in kinases: the case of PI3K-γ.

Francesco Luigi Gervasio, Obdulia Rabal, Julen Oyarzabal, 2012, Angewandte Chemie.

Detailed Exploration around 4-Aminoquinolines Chemical Space to Navigate the Lysine Methyltransferase G9a and DNA Methyltransferase Biological Spaces.

J. Martinez-Climent, F. Prósper, X. Agirre, 2018, Journal of medicinal chemistry.

Novel Scaffold Fingerprint (SFP): Applications in Scaffold Hopping and Scaffold-Based Selection of Diverse Compounds

Fares Ibrahim Amr, O. Rabal, J. Oyarzábal, 2015, J. Chem. Inf. Model..

Assessment of additive/nonadditive effects in structure-activity relationships: implications for iterative drug design.

Peter Willett, Valerie J Gillet, Julen Oyarzabal, 2008, Journal of medicinal chemistry.

In vivo, in vitro and in silico methods for small molecule transfer across the BBB.

J. Oyarzábal, J. Mensch, P. Augustijns, 2009, Journal of pharmaceutical sciences.

Pim 1 kinase inhibitor ETP-45299 suppresses cellular proliferation and synergizes with PI3K inhibition.

J. Oyarzábal, J. Leal, J. Bischoff, 2011, Cancer letters.

CHEMDNER challenge overview paper with summary tables of systems performance , methods , features and used resources : •

A. Valencia, F. Leitner, Martin Krallinger, 2014 .

Identification of ETP-46321, a potent and orally bioavailable PI3K α, δ inhibitor.

M. Barbacid, F. Mulero, P. Pizcueta, 2012, Bioorganic & medicinal chemistry letters.

Biologically Relevant Chemical Space Navigator: From Patent and Structure-Activity Relationship Analysis to Library Acquisition and Design

J. Oyarzábal, Obdulia Rabal, 2012, J. Chem. Inf. Model..

Epigenetic-based differentiation therapy for Acute Myeloid Leukemia

J. Martín-Subero, M. Calasanz, X. Agirre, 2024, Nature communications.

Design and Synthesis of Novel Epigenetic Inhibitors Targeting Histone Deacetylases, DNA Methyltransferase 1, and Lysine Methyltransferase G9a with In Vivo Efficacy in Multiple Myeloma.

F. Prósper, X. Agirre, J. Oyarzábal, 2021, Journal of medicinal chemistry.

AI is a viable alternative to high throughput screening: a 318-target study

Eva M García-Cuesta, Frederick S. Vizeacoumar, Stephen J. Capuzzi, 2024, Scientific reports.