Klara Valko

==Research==

==Research==

Valko's 1986 study compared the efficacy of microwave irradiation as a sample preparation method for chromatography with traditional approaches. This research highlighted its exceptional time and energy efficiency, particularly suited for rapid extractions in large sample series.{{Cite journal|title=Microwave extraction. A novel sample preparation method for chromatography|first1=K.|last1=Ganzler|first2=A.|last2=Salgó|first3=K.|last3=Valkó|date=December 26, 1986|journal=Journal of Chromatography|volume=371|pages=299–306|doi=10.1016/s0021-9673(01)94714-4|pmid=3558551}} In 1997, she invented the Chromatographic Hydrophobicity Index (CHI) based on reversed-phase HPLC retention times, offering a high-throughput approach for physicochemical profiling in drug design, demonstrating strong correlations with [[acetonitrile]] distribution and octanol/water partition coefficients.{{Cite journal|url=https://pubs.acs.org/doi/10.1021/ac961242d|title=Chromatographic Hydrophobicity Index by Fast-Gradient RP-HPLC: A High-Throughput Alternative to log P/log D|first1=Klára|last1=Valkó|first2=Chris|last2=Bevan|first3=Derek|last3=Reynolds|date=June 1, 1997|journal=Analytical Chemistry|volume=69|issue=11|pages=2022–2029|via=CrossRef|doi=10.1021/ac961242d|pmid=21639241 |url-access=subscription}} Her collaborative effort with GSK colleagues in 2003 outlined the development and validation of a rapid gradient HPLC method for determining Human Serum Albumin (HSA) binding of discovery compounds.{{Cite journal|title=Fast gradient HPLC method to determine compounds binding to human serum albumin. Relationships with octanol/water and immobilized artificial membrane lipophilicity|first1=Klara|last1=Valko|first2=Shenaz|last2=Nunhuck|first3=Chris|last3=Bevan|first4=Michael H.|last4=Abraham|first5=Derek P.|last5=Reynolds|date=November 29, 2003|journal=Journal of Pharmaceutical Sciences|volume=92|issue=11|pages=2236–2248|doi=10.1002/jps.10494|pmid=14603509}} In 2011, she proposed a novel approach, using calibrated HPLC retention times on biomimetic stationary phases to develop mechanistic models. This approach enabled estimating in vivo unbound volume of distribution (V(du)) and fraction unbound in tissue (f(ut)) during lead optimization, aiding consideration of in vitro potency and estimated in vivo pharmacokinetic distribution of compounds.{{Cite journal|title=Estimating unbound volume of distribution and tissue binding by in vitro HPLC-based human serum albumin and immobilised artificial membrane-binding measurements|first1=Klára L.|last1=Valkó|first2=Shenaz B.|last2=Nunhuck|first3=Alan P.|last3=Hill|date=March 29, 2011|journal=Journal of Pharmaceutical Sciences|volume=100|issue=3|pages=849–862|doi=10.1002/jps.22323|pmid=20891009}} In the same year, she explored the optimization of drug properties in drug discovery, introducing the drug efficiency index (DEI) as a marker of in vivo efficacy.{{Cite journal|title=Application of drug efficiency index in drug discovery: a strategy towards low therapeutic dose|first1=Montanari|last1=D|first2=Chiarparin|last2=E|first3=Gleeson|last3=Mp|first4=Braggio|last4=S|first5=Longhi|last5=R|first6=Valko|last6=K|first7=Rossi|last7=T|date=September 29, 2011|journal=Expert Opinion on Drug Discovery|volume=6|issue=9|pages=913–920 |doi=10.1517/17460441.2011.602968|pmid=22646214|s2cid=2167988 }} Moreover, her 2015 study explored developing and optimizing a high-throughput assay for directly measuring intracellular compound concentration in HeLa cells.{{Cite journal|title=Direct Measurement of Intracellular Compound Concentration by RapidFire Mass Spectrometry Offers Insights into Cell Permeability|first1=Laurie J.|last1=Gordon|first2=Morven|last2=Allen|first3=Per|last3=Artursson|first4=Michael M.|last4=Hann|first5=Bill J.|last5=Leavens|first6=André|last6=Mateus|first7=Simon|last7=Readshaw|first8=Klara|last8=Valko|first9=Gareth J.|last9=Wayne|first10=Andy|last10=West|date=February 29, 2016|journal=Journal of Biomolecular Screening|volume=21|issue=2|pages=156–164|doi=10.1177/1087057115604141|pmid=26336900|doi-access=free}}

Valko's 1986 study compared the efficacy of microwave irradiation as a sample preparation method for chromatography with traditional approaches. This research highlighted its exceptional time and energy efficiency, particularly suited for rapid extractions in large sample series.{{Cite journal|title=Microwave extraction. A novel sample preparation method for chromatography|first1=K.|last1=Ganzler|first2=A.|last2=Salgó|first3=K.|last3=Valkó|date=December 26, 1986|journal=Journal of Chromatography|volume=371|pages=299–306|doi=10.1016/s0021-9673(01)94714-4|pmid=3558551}} In 1997, she invented the Chromatographic Hydrophobicity Index (CHI) based on reversed-phase HPLC retention times, offering a high-throughput approach for physicochemical profiling in drug design, demonstrating strong correlations with [[acetonitrile]] distribution and octanol/water partition coefficients.{{Cite journal|url=https://pubs.acs.org/doi/10.1021/ac961242d|title=Chromatographic Hydrophobicity Index by Fast-Gradient RP-HPLC: A High-Throughput Alternative to log P/log D|first1=Klára|last1=Valkó|first2=Chris|last2=Bevan|first3=Derek|last3=Reynolds|date=June 1, 1997|journal=Analytical Chemistry|volume=69|issue=11|pages=2022–2029|via=CrossRef|doi=10.1021/ac961242d|pmid=21639241 |url-access=subscription}} Her collaborative effort with GSK colleagues in 2003 outlined the development and validation of a rapid gradient HPLC method for determining [[Human serum albumin|Human Serum Albumin]] (HSA) binding of discovery compounds.{{Cite journal|title=Fast gradient HPLC method to determine compounds binding to human serum albumin. Relationships with octanol/water and immobilized artificial membrane lipophilicity|first1=Klara|last1=Valko|first2=Shenaz|last2=Nunhuck|first3=Chris|last3=Bevan|first4=Michael H.|last4=Abraham|first5=Derek P.|last5=Reynolds|date=November 29, 2003|journal=Journal of Pharmaceutical Sciences|volume=92|issue=11|pages=2236–2248|doi=10.1002/jps.10494|pmid=14603509}} In 2011, she proposed a novel approach, using calibrated HPLC retention times on biomimetic stationary phases to develop mechanistic models. This approach enabled estimating in vivo unbound [[volume of distribution]] (V(du)) and fraction unbound in tissue (f(ut)) during lead optimization, aiding consideration of in vitro potency and estimated in vivo pharmacokinetic distribution of compounds.{{Cite journal|title=Estimating unbound volume of distribution and tissue binding by in vitro HPLC-based human serum albumin and immobilised artificial membrane-binding measurements|first1=Klára L.|last1=Valkó|first2=Shenaz B.|last2=Nunhuck|first3=Alan P.|last3=Hill|date=March 29, 2011|journal=Journal of Pharmaceutical Sciences|volume=100|issue=3|pages=849–862|doi=10.1002/jps.22323|pmid=20891009}} In the same year, she explored the optimization of drug properties in drug discovery, introducing the drug efficiency index (DEI) as a marker of in vivo efficacy.{{Cite journal|title=Application of drug efficiency index in drug discovery: a strategy towards low therapeutic dose|first1=Montanari|last1=D|first2=Chiarparin|last2=E|first3=Gleeson|last3=Mp|first4=Braggio|last4=S|first5=Longhi|last5=R|first6=Valko|last6=K|first7=Rossi|last7=T|date=September 29, 2011|journal=Expert Opinion on Drug Discovery|volume=6|issue=9|pages=913–920 |doi=10.1517/17460441.2011.602968|pmid=22646214|s2cid=2167988 }} Moreover, her 2015 study explored developing and optimizing a high-throughput assay for directly measuring intracellular compound concentration in HeLa cells.{{Cite journal|title=Direct Measurement of Intracellular Compound Concentration by RapidFire Mass Spectrometry Offers Insights into Cell Permeability|first1=Laurie J.|last1=Gordon|first2=Morven|last2=Allen|first3=Per|last3=Artursson|first4=Michael M.|last4=Hann|first5=Bill J.|last5=Leavens|first6=André|last6=Mateus|first7=Simon|last7=Readshaw|first8=Klara|last8=Valko|first9=Gareth J.|last9=Wayne|first10=Andy|last10=West|date=February 29, 2016|journal=Journal of Biomolecular Screening|volume=21|issue=2|pages=156–164|doi=10.1177/1087057115604141|pmid=26336900|doi-access=free}}

Investigating the use of standardized HPLC methods, Valko's 2016 research suggested that Chromatographic properties measured at early stages of the drug discovery process can assess lipophilicity, oral absorption, volume of distribution, drug efficiency, and even early dose estimation.{{Cite journal|title=Lipophilicity and biomimetic properties measured by HPLC to support drug discovery|first=Valkó|last=Kl|date=October 25, 2016|journal=Journal of Pharmaceutical and Biomedical Analysis|volume=130|pages=35–54 |doi=10.1016/j.jpba.2016.04.009|pmid=27084527}} In related research, she introduced standardized procedures for accelerating drug discovery by evaluating in vivo distribution and non-specific binding through chromatographic profiling of analogs, highlighting the advantages over traditional metrics such as Ligand Lipophilicity Efficiency (LLE).{{Cite journal|url=https://pub.iapchem.org/ojs/index.php/admet/article/view/373|title=In vitro membrane binding and protein binding (IAM MB/PB technology) to estimate in vivo distribution: applications in early drug discovery|first1=Klara Livia|last1=Valko|first2=Simon P.|last2=Teague|first3=Charles|last3=Pidgeon|date=March 24, 2017|journal=ADMET and DMPK|volume=5|issue=1|pages=14–38|via=pub.iapchem.org|doi=10.5599/admet.5.1.373|doi-access=free}} Later, her 2018 work tackled peptide therapeutic challenges by assessing biomimetic properties like lipophilicity and membrane affinity via High-Performance Liquid Chromatography, using chemically bonded protein and immobilized artificial membrane stationary phases.{{Cite journal|url=https://pub.iapchem.org/ojs/index.php/admet/article/view/544|title=Application of biomimetic HPLC to estimate lipophilicity, protein and phospholipid binding of potential peptide therapeutics|first1=Klara Livia|last1=Valko|first2=Gabriela|last2=Ivanova-Berndt|first3=Paul|last3=Beswick|first4=Mark|last4=Kindey|first5=Dorothy|last5=Ko|date=June 16, 2018|journal=ADMET and DMPK|volume=6|issue=2|pages=162–175|via=pub.iapchem.org|doi=10.5599/admet.544|doi-access=free}} Her 2021 suggested that membrane and alpha-1-acid [[glycoprotein]] retention can be considered as promising indices for assessing the ecotoxicological risk of drugs, with membrane models showing superior performance compared to those derived from the traditional octanol-water system.{{Cite web|url=https://www.tandfonline.com/doi/full/10.1080/02772248.2021.2005065#:~:text=4.-,Conclusions,of%20fish%20and%20water%20flea.|title=The use of biomimetic chromatography to predict acute aquatic toxicity of pharmaceutical compounds: Toxicological & Environmental Chemistry: Vol 104, No 1|doi=10.1080/02772248.2021.2005065 |s2cid=244046500 }} In addition, she also proposed a model using biomimetic HPLC methods and measured binding properties to predict hERG inhibition, addressing early screening for potential cardiotoxicity and reducing late-stage failures in drug discovery.{{Cite journal|title=Prediction of hERG inhibition of drug discovery compounds using biomimetic HPLC measurements|first1=Chrysanthos|last1=Stergiopoulos|first2=Fotios|last2=Tsopelas|first3=Klara|last3=Valko|date=June 6, 2021|journal=ADMET and DMPK|volume=9|issue=3|pages=191–207|doi=10.5599/admet.995|pmid=35300361|pmc=8920097}}

Investigating the use of standardized HPLC methods, Valko's 2016 research suggested that Chromatographic properties measured at early stages of the drug discovery process can assess lipophilicity, oral absorption, volume of distribution, drug efficiency, and even early dose estimation.{{Cite journal|title=Lipophilicity and biomimetic properties measured by HPLC to support drug discovery|first=Valkó|last=Kl|date=October 25, 2016|journal=Journal of Pharmaceutical and Biomedical Analysis|volume=130|pages=35–54 |doi=10.1016/j.jpba.2016.04.009|pmid=27084527}} In related research, she introduced standardized procedures for accelerating drug discovery by evaluating in vivo distribution and non-specific binding through chromatographic profiling of analogs, highlighting the advantages over traditional metrics such as Ligand Lipophilicity Efficiency (LLE).{{Cite journal|url=https://pub.iapchem.org/ojs/index.php/admet/article/view/373|title=In vitro membrane binding and protein binding (IAM MB/PB technology) to estimate in vivo distribution: applications in early drug discovery|first1=Klara Livia|last1=Valko|first2=Simon P.|last2=Teague|first3=Charles|last3=Pidgeon|date=March 24, 2017|journal=ADMET and DMPK|volume=5|issue=1|pages=14–38|via=pub.iapchem.org|doi=10.5599/admet.5.1.373|doi-access=free}} Later, her 2018 work tackled peptide therapeutic challenges by assessing biomimetic properties like lipophilicity and membrane affinity via High-Performance Liquid Chromatography, using chemically bonded protein and immobilized artificial membrane stationary phases.{{Cite journal|url=https://pub.iapchem.org/ojs/index.php/admet/article/view/544|title=Application of biomimetic HPLC to estimate lipophilicity, protein and phospholipid binding of potential peptide therapeutics|first1=Klara Livia|last1=Valko|first2=Gabriela|last2=Ivanova-Berndt|first3=Paul|last3=Beswick|first4=Mark|last4=Kindey|first5=Dorothy|last5=Ko|date=June 16, 2018|journal=ADMET and DMPK|volume=6|issue=2|pages=162–175|via=pub.iapchem.org|doi=10.5599/admet.544|doi-access=free}} Her 2021 suggested that membrane and alpha-1-acid [[glycoprotein]] retention can be considered as promising indices for assessing the ecotoxicological risk of drugs, with membrane models showing superior performance compared to those derived from the traditional octanol-water system.{{Cite web|url=https://www.tandfonline.com/doi/full/10.1080/02772248.2021.2005065#:~:text=4.-,Conclusions,of%20fish%20and%20water%20flea.|title=The use of biomimetic chromatography to predict acute aquatic toxicity of pharmaceutical compounds: Toxicological & Environmental Chemistry: Vol 104, No 1|doi=10.1080/02772248.2021.2005065 |s2cid=244046500 }} In addition, she also proposed a model using biomimetic HPLC methods and measured binding properties to predict hERG inhibition, addressing early screening for potential cardiotoxicity and reducing late-stage failures in drug discovery.{{Cite journal|title=Prediction of hERG inhibition of drug discovery compounds using biomimetic HPLC measurements|first1=Chrysanthos|last1=Stergiopoulos|first2=Fotios|last2=Tsopelas|first3=Klara|last3=Valko|date=June 6, 2021|journal=ADMET and DMPK|volume=9|issue=3|pages=191–207|doi=10.5599/admet.995|pmid=35300361|pmc=8920097}}