Dr. Leticia Manen-Freixa currently holds the position of R&D Scientist in Cheminformatics & Drug Design at IDIBELL, where she also serves as the Computational Lab Manager. This role has provided her with an invaluable opportunity to specialize in a diverse range of areas of Drug Discovery in the oncology R&D field, including polypharmacology, off-target prediction, and the design of antineoplastic drugs. Beyond this, she has delved into the world of artificial intelligence, with a keen focus on Machine Learning, Deep Learning, and NLP. She obtained her PhD in Chemistry and Chemical Engineering from Universitat Ramon Llull in 2022. Her thesis project was positioned in the field of medicinal chemistry, and due to her significant contributions, her profile could be interdisciplinarily described both as a chemoinformatic and organic chemist. She holds a Degree in Chemistry, a MSc in Teacher Training for Secondary School, and a MSc in Pharmaceutical Chemistry.
EDUCATION
PhD in Chemistry & Chemical Engineering (IQS School of Engineering - URL) 2018-2022
Master’s Degree in Pharmaceutical Chemistry (IQS School of Engineering - URL) 2017-2018
Master’s Degree in Formation Of Tearchers For Secondary School (UNIR) 2017-2018
Bachelor of Science: Chemistry (IQS School of Engineering - URL) 2012-2016
RESEARCH, TEACHING, or OTHER INTERESTS
Chemistry, Organic Chemistry, Drug Discovery, Pharmaceutical Science
5
Scopus Publications
34
Scholar Citations
3
Scholar h-index
1
Scholar i10-index
Scopus Publications
Concurrence of FGFR1 mutations modulates oncogenesis in glioneuronal tumors Jacopo Boni, Míriam Fernández-González, HyeRim Han, Carla Roca, Cassandra J Wong, Cristina Rioja, Clara Nogué, Leticia Manen-Freixa, Jonathan Boulais, Endika Torres-Urtizberea, Antonio Gomez, Martin Hasselblatt, Roger Estrada-Tejedor, Albert A Antolin, Islam E Elkholi, Nada Jabado, Jean-François Côté, Anne-Claude Gingras, Barbara Rivera EMBO Journal, 2025 FGFR1 genetic alterations are associated with brain malignancies, including FGFR1 mutations in familial and sporadic cases of low-grade glioneuronal tumors, suggesting intrinsic mechanisms of selective pressure toward FGFR1 multiple events arising in the context of a quiet genome. To decipher the molecular mechanisms triggered by multiple concurrent FGFR1 mutations, we have mapped the proximal interactome of wild-type, single- and double-mutant FGFR1 proteins through a BioID-MS approach. Our data reveal novel oncogenic functionality for the two hotspot mutations N546K and K656E, linked to evasion of lysosomal degradation. Further, we identified a modulatory tumor-suppressive role for the susceptibility variant R661P, which hampers the oncogenic potential of both hotspot N546K and K656E mutations by rescuing receptor degradation and reducing N546K affinity for the downstream effector PLCγ. Introducing the R661P missense variant was sufficient to abolish self-renewal capacity of oligodendroglioma cells and downregulate genes involved in neurodevelopment and neuro-glial cell fate decisions, both aspects overcome in the double mutants. This study sheds light on contextual oncogenic effects associated with FGFR1 alterations and their recurrence in low-mutation burden and therapy naive tumors.
Short-term exposure to environmental levels of nicotine and cotinine impairs visual motor response in zebrafish larvae through a similar mode of action: Exploring the potential role of zebrafish α7 nAChR Marina Bellot, Leticia Manen-Freixa, Eva Prats, Juliette Bedrossiantz, Carlos Barata, Cristian Gómez-Canela, Albert A. Antolin, Demetrio Raldúa Science of the Total Environment, 2024 The current view is that environmental levels of nicotine and cotinine, commonly in the ng/L range, are safe for aquatic organisms. In this study, 7 days post-fertilization zebrafish embryos have been exposed for 24 h to a range of environmental concentrations of nicotine (2.0 ng/L-2.5 μg/L) and cotinine (50 pg/L-10 μg/L), as well as to a binary mixture of these emerging pollutants. Nicotine exposure led to hyperactivity, decreased vibrational startle response and increased non-associative learning. However, the more consistent effect found for both nicotine and cotinine was a significant increase in light-off visual motor response (VMR). The effect of both pollutants on this behavior occurred through a similar mode of action, as the joint effects of the binary mixture of both chemicals were consistent with the concentration addition concept predictions. The results from docking studies suggest that the effect of nicotine and cotinine on light-off VMR could be mediated by zebrafish α7 nAChR expressed in retina. The results presented in this study emphasize the need to revisit the environmental risk assessment of chemicals including additional ecologically relevant sublethal endpoints.
Polypharmacology prediction: the long road toward comprehensively anticipating small-molecule selectivity to de-risk drug discovery Leticia Manen-Freixa, Albert A. Antolin Expert Opinion on Drug Discovery, 2024 INTRODUCTION Small molecules often bind to multiple targets, a behavior termed polypharmacology. Anticipating polypharmacology is essential for drug discovery since unknown off-targets can modulate safety and efficacy - profoundly affecting drug discovery success. Unfortunately, experimental methods to assess selectivity present significant limitations and drugs still fail in the clinic due to unanticipated off-targets. Computational methods are a cost-effective, complementary approach to predict polypharmacology. AREAS COVERED This review aims to provide a comprehensive overview of the state of polypharmacology prediction and discuss its strengths and limitations, covering both classical cheminformatics methods and bioinformatic approaches. The authors review available data sources, paying close attention to their different coverage. The authors then discuss major algorithms grouped by the types of data that they exploit using selected examples. EXPERT OPINION Polypharmacology prediction has made impressive progress over the last decades and contributed to identify many off-targets. However, data incompleteness currently limits most approaches to comprehensively predict selectivity. Moreover, our limited agreement on model assessment challenges the identification of the best algorithms - which at present show modest performance in prospective real-world applications. Despite these limitations, the exponential increase of multidisciplinary Big Data and AI hold much potential to better polypharmacology prediction and de-risk drug discovery.
Deconstructing Markush: Improving the R&D Efficiency Using Library Selection in Early Drug Discovery Leticia Manen-Freixa, José I. Borrell, Jordi Teixidó, Roger Estrada-Tejedor Pharmaceuticals, 2022 Most of the product patents claim a large number of compounds based on a Markush structure. However, the identification and optimization of new principal active ingredients is frequently driven by a simple Free Wilson approach, leading to a highly focused study only involving the chemical space nearby a hit compound. This fact raises the question: do the tested compounds described in patents really reflect the full molecular diversity described in the Markush structure? In this study, we contrast the performance of rational selection to conventional approaches in seven real-case patents, assessing their ability to describe the patent’s chemical space. Results demonstrate that the integration of computer-aided library selection methods in the early stages of the drug discovery process would boost the identification of new potential hits across the chemical space.
RECENT SCHOLAR PUBLICATIONS
Concurrence of FGFR1 mutations modulates oncogenesis in glioneuronal tumors J Boni, M Fernández-González, HR Han, C Roca, CJ Wong, C Rioja, ... The EMBO Journal 44 (24), 7513 , 2025 2025.0
META-PRIME: Repurposing Drug Metabolites in Precision Oncology using AI L Ruvo, L Manen-Freixa, S Santos, L Josa-Culleré, C Serra, A Llebaria, ... RExPO25 Conference , 2025 2025.0
Leveraging cancer drug metabolites for precision drug repurposing AA Antolin, L Ruvo, L Manen-Freixa, S Santos, J Brea, MI Loza, ... RExPO25 Conference , 2025 2025.0
Multiple FGFR1 mutations modulate tumorigenic mechanisms in glioneuronal tumors J Boni, M Fernández-González, HR Han, C Roca, CJ Wong, C Rioja, ... bioRxiv, 2025.05. 27.654799 , 2025 2025.0
Polypharmacology prediction: the long road toward comprehensively anticipating small-molecule selectivity to de-risk drug discovery L Manen-Freixa, AA Antolin Expert Opinion on Drug Discovery 19 (9), 1043-1069 , 2024 2024.0 Citations: 9
Exploring the unexplored chemical space: Rational identification of new Tafenoquine analogs with antimalarial properties L Manen-Freixa, S Moliner-Cubel, FJ Gamo, B Crespo, JI Borrell, ... Bioorganic Chemistry 148, 107472 , 2024 2024.0 Citations: 2
Short-term exposure to environmental levels of nicotine and cotinine impairs visual motor response in zebrafish larvae through a similar mode of action: Exploring the potential … M Bellot, L Manen-Freixa, E Prats, J Bedrossiantz, C Barata, ... Science of the Total Environment 912, 169301 , 2024 2024.0 Citations: 18
Exploring Molecular Diversity: There is Plenty of Room at Markush's L Manén Freixa Universitat Ramon Llull , 2022 2022.0
Deconstructing Markush: improving the R&D efficiency using library selection in early drug discovery L Manen-Freixa, JI Borrell, J Teixidó, R Estrada-Tejedor Pharmaceuticals 15 (9), 1159 , 2022 2022.0 Citations: 5
Exploring the Unexplored Tafenoquine's Chemical Space: Rational Identification of New Tafenoquine Analogues with Antimalarial Properties L Manen-Freixa, S Moliner-Cubel, FJ Gamo, B Crespo, JI Borrell, ... Available at SSRN 4773572 , 0
MOST CITED SCHOLAR PUBLICATIONS
Short-term exposure to environmental levels of nicotine and cotinine impairs visual motor response in zebrafish larvae through a similar mode of action: Exploring the potential … M Bellot, L Manen-Freixa, E Prats, J Bedrossiantz, C Barata, ... Science of the Total Environment 912, 169301 , 2024 2024.0 Citations: 18
Polypharmacology prediction: the long road toward comprehensively anticipating small-molecule selectivity to de-risk drug discovery L Manen-Freixa, AA Antolin Expert Opinion on Drug Discovery 19 (9), 1043-1069 , 2024 2024.0 Citations: 9
Deconstructing Markush: improving the R&D efficiency using library selection in early drug discovery L Manen-Freixa, JI Borrell, J Teixidó, R Estrada-Tejedor Pharmaceuticals 15 (9), 1159 , 2022 2022.0 Citations: 5
Exploring the unexplored chemical space: Rational identification of new Tafenoquine analogs with antimalarial properties L Manen-Freixa, S Moliner-Cubel, FJ Gamo, B Crespo, JI Borrell, ... Bioorganic Chemistry 148, 107472 , 2024 2024.0 Citations: 2
Concurrence of FGFR1 mutations modulates oncogenesis in glioneuronal tumors J Boni, M Fernández-González, HR Han, C Roca, CJ Wong, C Rioja, ... The EMBO Journal 44 (24), 7513 , 2025 2025.0
META-PRIME: Repurposing Drug Metabolites in Precision Oncology using AI L Ruvo, L Manen-Freixa, S Santos, L Josa-Culleré, C Serra, A Llebaria, ... RExPO25 Conference , 2025 2025.0
Leveraging cancer drug metabolites for precision drug repurposing AA Antolin, L Ruvo, L Manen-Freixa, S Santos, J Brea, MI Loza, ... RExPO25 Conference , 2025 2025.0
Multiple FGFR1 mutations modulate tumorigenic mechanisms in glioneuronal tumors J Boni, M Fernández-González, HR Han, C Roca, CJ Wong, C Rioja, ... bioRxiv, 2025.05. 27.654799 , 2025 2025.0
Exploring Molecular Diversity: There is Plenty of Room at Markush's L Manén Freixa Universitat Ramon Llull , 2022 2022.0
Exploring the Unexplored Tafenoquine's Chemical Space: Rational Identification of New Tafenoquine Analogues with Antimalarial Properties L Manen-Freixa, S Moliner-Cubel, FJ Gamo, B Crespo, JI Borrell, ... Available at SSRN 4773572 , 0
