Sergio Wittlin
YOU?
Author Swipe
View article: Medicinal Chemistry Progression of Sapanisertib, the Anticancer and Dual <i>Plasmodium</i> Phosphatidylinositol 4-Kinase Beta and cGMP-Dependent Protein Kinase Inhibitor, for Malaria
Medicinal Chemistry Progression of Sapanisertib, the Anticancer and Dual <i>Plasmodium</i> Phosphatidylinositol 4-Kinase Beta and cGMP-Dependent Protein Kinase Inhibitor, for Malaria Open
We recently demonstrated that the anticancer human mTOR inhibitor sapanisertib displays antimalarial activity in a malaria mouse model of infection and inhibits multiple Plasmodium kinases, including the high-value targets phosphatidylinos…
View article: Cell-Based Progression of Spiroindoline Phenotypic Hits Leads to the Identification of Compounds with Diverging Parasitological Profiles against the Human Malaria Parasite <i>Plasmodium falciparum</i>
Cell-Based Progression of Spiroindoline Phenotypic Hits Leads to the Identification of Compounds with Diverging Parasitological Profiles against the Human Malaria Parasite <i>Plasmodium falciparum</i> Open
In the search for novel chemotypes with high sp3 character and activity against the human malaria parasite Plasmodium falciparum, a spiroindoline series was identified from a phenotypic high-throughput screening campaign. The spiroindoline…
View article: The ATM Kinase Inhibitor AZD0156 Is a Potent Inhibitor of <i>Plasmodium</i> Phosphatidylinositol 4‐Kinase (PI4Kβ) and Is an Attractive Candidate for Medicinal Chemistry Optimization Against Malaria
The ATM Kinase Inhibitor AZD0156 Is a Potent Inhibitor of <i>Plasmodium</i> Phosphatidylinositol 4‐Kinase (PI4Kβ) and Is an Attractive Candidate for Medicinal Chemistry Optimization Against Malaria Open
New compounds targeting human malaria parasites are critical for effective malaria control and elimination. Here, we pursued the imidazoquinolinone AZD0156 (MMV1580483), a human ataxia‐telangiectasia mutated (ATM) kinase inhibitor that com…
View article: The ATM Kinase Inhibitor AZD0156 Is a Potent Inhibitor of <i>Plasmodium</i> Phosphatidylinositol 4‐Kinase (PI4Kβ) and Is an Attractive Candidate for Medicinal Chemistry Optimization Against Malaria
The ATM Kinase Inhibitor AZD0156 Is a Potent Inhibitor of <i>Plasmodium</i> Phosphatidylinositol 4‐Kinase (PI4Kβ) and Is an Attractive Candidate for Medicinal Chemistry Optimization Against Malaria Open
New compounds targeting human malaria parasites are critical for effective malaria control and elimination. Here, we pursued the imidazoquinolinone AZD0156 (MMV1580483), a human ataxia‐telangiectasia mutated (ATM) kinase inhibitor that com…
View article: A potent and selective reaction hijacking inhibitor of Plasmodium falciparum tyrosine tRNA synthetase exhibits single dose oral efficacy in vivo
A potent and selective reaction hijacking inhibitor of Plasmodium falciparum tyrosine tRNA synthetase exhibits single dose oral efficacy in vivo Open
The Plasmodium falciparum cytoplasmic tyrosine tRNA synthetase ( Pf TyrRS) is an attractive drug target that is susceptible to reaction-hijacking by AMP-mimicking nucleoside sulfamates. We previously identified an exemplar pyrazolopyrimidi…
View article: Addressing the Intracellular Vestibule of the Plasmodial Lactate Transporter PfFNT by p-Substituted Inhibitors Amplifies In Vitro Activity
Addressing the Intracellular Vestibule of the Plasmodial Lactate Transporter PfFNT by p-Substituted Inhibitors Amplifies In Vitro Activity Open
Inhibition of the lactate transporter PfFNT is a valid novel mode of action against malaria parasites. Current pyridine-substituted pentafluoro-3-hydroxy-pent-2-en-1-ones act as substrate analogs with submicromolar EC50 in vitro, and >99.7…
View article: Total Synthesis of Tosyl‐Samroiyotmycin A and Its Biological Profiling
Total Synthesis of Tosyl‐Samroiyotmycin A and Its Biological Profiling Open
A total synthesis of the enantiopure syn,syn‐ tosyl‐samroiyotmycin A, a C 2 ‐symmetric 20‐membered antimalarial macrodiolide with syn,syn‐ configuration of the 8,24‐dihydroxy‐9,25‐dimethyl units and it's enantiopure anti,anti‐ derivative i…
View article: Identification of potent and reversible piperidine carboxamides that are species-selective orally active proteasome inhibitors to treat malaria
Identification of potent and reversible piperidine carboxamides that are species-selective orally active proteasome inhibitors to treat malaria Open
Malaria remains a global health concern as drug resistance threatens treatment programs. We identified a piperidine carboxamide (SW042) with anti-malarial activity by phenotypic screening. Selection of SW042-resistant Plasmodium falciparum…
View article: A potent and selective reaction hijacking inhibitor of<i>Plasmodium falciparum</i>tyrosine tRNA synthetase exhibits single dose oral efficacy<i>in vivo</i>
A potent and selective reaction hijacking inhibitor of<i>Plasmodium falciparum</i>tyrosine tRNA synthetase exhibits single dose oral efficacy<i>in vivo</i> Open
The Plasmodium falciparum cytoplasmic tyrosine tRNA synthetase ( Pf TyrRS) is an attractive drug target that is susceptible to reaction-hijacking by AMP-mimicking nucleoside sulfamates. We previously identified an exemplar pyrazolopyrimidi…
View article: Optimization of pyrazolopyridine 4-carboxamides with potent antimalarial activity for which resistance is associated with the P. falciparum transporter ABCI3
Optimization of pyrazolopyridine 4-carboxamides with potent antimalarial activity for which resistance is associated with the P. falciparum transporter ABCI3 Open
Emerging resistance to current antimalarials is reducing their effectiveness and therefore there is a need to develop new antimalarial therapies. Toward this goal, high throughput screens against the P. falciparum asexual parasite identifi…
View article: 2,8-Disubstituted-1,5-naphthyridines as Dual Inhibitors of <i>Plasmodium falciparum</i> Phosphatidylinositol-4-kinase and Hemozoin Formation with <i>In Vivo</i> Efficacy
2,8-Disubstituted-1,5-naphthyridines as Dual Inhibitors of <i>Plasmodium falciparum</i> Phosphatidylinositol-4-kinase and Hemozoin Formation with <i>In Vivo</i> Efficacy Open
Structure-activity relationship studies of 2,8-disubstituted-1,5-naphthyridines, previously reported as potent inhibitors of Plasmodium falciparum (Pf) phosphatidylinositol-4-kinase β (PI4K), identified 1,5-naphthyridines with basic groups…
View article: Chemoproteomics validates selective targeting of Plasmodium M1 alanyl aminopeptidase as an antimalarial strategy
Chemoproteomics validates selective targeting of Plasmodium M1 alanyl aminopeptidase as an antimalarial strategy Open
New antimalarial drug candidates that act via novel mechanisms are urgently needed to combat malaria drug resistance. Here, we describe the multi-omic chemical validation of Plasmodium M1 alanyl metalloaminopeptidase as an attractive drug …
View article: Reviewer #2 (Public Review): Chemoproteomics validates selective targeting of Plasmodium M1 alanyl aminopeptidase as an antimalarial strategy
Reviewer #2 (Public Review): Chemoproteomics validates selective targeting of Plasmodium M1 alanyl aminopeptidase as an antimalarial strategy Open
New antimalarial drug candidates that act via novel mechanisms are urgently needed to combat malaria drug resistance. Here, we describe the multi-omic chemical validation of Plasmodium M1 alanyl metalloaminopeptidase as an attractive drug …
View article: Author response: Chemoproteomics validates selective targeting of Plasmodium M1 alanyl aminopeptidase as an antimalarial strategy
Author response: Chemoproteomics validates selective targeting of Plasmodium M1 alanyl aminopeptidase as an antimalarial strategy Open
New antimalarial drug candidates that act via novel mechanisms are urgently needed to combat malaria drug resistance. Here, we describe the multi-omic chemical validation of Plasmodium M1 alanyl metalloaminopeptidase as an attractive drug …
View article: Reviewer #3 (Public Review): Chemoproteomics validates selective targeting of Plasmodium M1 alanyl aminopeptidase as an antimalarial strategy
Reviewer #3 (Public Review): Chemoproteomics validates selective targeting of Plasmodium M1 alanyl aminopeptidase as an antimalarial strategy Open
New antimalarial drug candidates that act via novel mechanisms are urgently needed to combat malaria drug resistance. Here, we describe the multi-omic chemical validation of Plasmodium M1 alanyl metalloaminopeptidase as an attractive drug …
View article: Chemoproteomics validates selective targeting of Plasmodium M1 alanyl aminopeptidase as an antimalarial strategy
Chemoproteomics validates selective targeting of Plasmodium M1 alanyl aminopeptidase as an antimalarial strategy Open
New antimalarial drug candidates that act via novel mechanisms are urgently needed to combat malaria drug resistance. Here, we describe the multi-omic chemical validation of Plasmodium M1 alanyl metalloaminopeptidase as an attractive drug …
View article: Reviewer #1 (Public Review): Chemoproteomics validates selective targeting of Plasmodium M1 alanyl aminopeptidase as an antimalarial strategy
Reviewer #1 (Public Review): Chemoproteomics validates selective targeting of Plasmodium M1 alanyl aminopeptidase as an antimalarial strategy Open
New antimalarial drug candidates that act via novel mechanisms are urgently needed to combat malaria drug resistance. Here, we describe the multi-omic chemical validation of Plasmodium M1 alanyl metalloaminopeptidase as an attractive drug …
View article: In vivo antimalarial efficacy of Artemisia afra powder suspensions
In vivo antimalarial efficacy of Artemisia afra powder suspensions Open
Our experiments conducted in mice do not support the pro-drug hypothesis.
View article: On-target, dual aminopeptidase inhibition provides cross-species antimalarial activity
On-target, dual aminopeptidase inhibition provides cross-species antimalarial activity Open
To combat the global burden of malaria, development of new drugs to replace or complement current therapies is urgently required. Here, we show that the compound MMV1557817 is a selective, nanomolar inhibitor of both Plasmodium falciparum …
View article: Incomplete Plasmodium falciparum growth inhibition following piperaquine treatment translates into increased parasite viability in the in vitro parasite reduction ratio assay
Incomplete Plasmodium falciparum growth inhibition following piperaquine treatment translates into increased parasite viability in the in vitro parasite reduction ratio assay Open
Antimalarial resistance to the first-line partner drug piperaquine (PPQ) threatens the effectiveness of artemisinin-based combination therapy. In vitro piperaquine resistance is characterized by incomplete growth inhibition, i.e. increased…
View article: Chemoproteomics validates selective targeting of Plasmodium M1 alanyl aminopeptidase as an antimalarial strategy
Chemoproteomics validates selective targeting of Plasmodium M1 alanyl aminopeptidase as an antimalarial strategy Open
New antimalarial drug candidates that act via novel mechanisms are urgently needed to combat malaria drug resistance. Here, we describe the multi-omic chemical validation of Plasmodium M1 alanyl metalloaminopeptidase as an attractive drug …
View article: Next Generation Chemiluminescent Probes for Antimalarial Drug Discovery
Next Generation Chemiluminescent Probes for Antimalarial Drug Discovery Open
Malaria is caused by parasites of the Plasmodium genus and remains one of the most pressing human health problems. The spread of parasites resistant to or partially resistant to single or multiple drugs, including frontline antimalarial ar…
View article: Activity refinement of aryl amino acetamides that target the P. falciparum STAR-related lipid transfer 1 protein
Activity refinement of aryl amino acetamides that target the P. falciparum STAR-related lipid transfer 1 protein Open
Malaria is a devastating disease that causes significant morbidity worldwide. The development of new antimalarial chemotypes is urgently needed because of the emergence of resistance to frontline therapies. Independent phenotypic screening…
View article: hERG, <i>Plasmodium</i> Life Cycle, and Cross Resistance Profiling of New Azabenzimidazole Analogues of Astemizole
hERG, <i>Plasmodium</i> Life Cycle, and Cross Resistance Profiling of New Azabenzimidazole Analogues of Astemizole Open
Toward addressing the cardiotoxicity liability associated with the antimalarial drug astemizole (AST, hERG IC50 = 0.0042 μM) and its derivatives, we designed and synthesized analogues based on compound 1 (Pf NF54 IC50 = 0.012 μM; hERG IC50…
View article: Reviewer #1 (Public Review): Chemoproteomics validates selective targeting of Plasmodium M1 alanyl aminopeptidase as a cross-species strategy to treat malaria
Reviewer #1 (Public Review): Chemoproteomics validates selective targeting of Plasmodium M1 alanyl aminopeptidase as a cross-species strategy to treat malaria Open
New antimalarial drug candidates that act via novel mechanisms are urgently needed to combat malaria drug resistance. Here, we describe the multi-omic chemical validation of Plasmodium M1 alanyl metalloaminopeptidase as an attractive drug …
View article: Chemoproteomics validates selective targeting of Plasmodium M1 alanyl aminopeptidase as an antimalarial strategy
Chemoproteomics validates selective targeting of Plasmodium M1 alanyl aminopeptidase as an antimalarial strategy Open
New antimalarial drug candidates that act via novel mechanisms are urgently needed to combat malaria drug resistance. Here, we describe the multi-omic chemical validation of Plasmodium M1 alanyl metalloaminopeptidase as an attractive drug …
View article: Reviewer #3 (Public Review): Chemoproteomics validates selective targeting of Plasmodium M1 alanyl aminopeptidase as a cross-species strategy to treat malaria
Reviewer #3 (Public Review): Chemoproteomics validates selective targeting of Plasmodium M1 alanyl aminopeptidase as a cross-species strategy to treat malaria Open
New antimalarial drug candidates that act via novel mechanisms are urgently needed to combat malaria drug resistance. Here, we describe the multi-omic chemical validation of Plasmodium M1 alanyl metalloaminopeptidase as an attractive drug …