Activities and Technologies

Design, construction and screening of encoded combinatorial libraries, for the identification of small molecule ligands against disease targets. Philochem is a leader in the field of DNA-encoded chemical libraries


Discovery and validation of pharmaceutical targets for ligand-based pharmacodelivery. Philochem uses state-of-the-art chemical proteomics technologies for the identification of accessible targets and for the characterization of the mechanism of action

Development of small molecule therapeutics, with the potential to achieve an unprecedented level of activity and selectivity. Philochem is performing pioneering work for the ligand-based delivery of drugs, radionuclides and immunomodulators.

Encoded Combinatorial Libraries


The discovery of small organic ligands to protein targets has been traditionally performed by screening very large sets of organic molecules (termed “chemical libraries”), one by one, using high-throughput screening procedures. The assembly of such libraries is very expensive and time consuming. While the value of high-throughput library screening has been demonstrated in various pharmaceutical applications, it is not uncommon that binding molecules of sufficient affinity and specificity (called “hits”) cannot be discovered using conventional screening campaigns.

In light of these considerations, considerable efforts have been devoted to the establishment of encoded libraries which enable the construction and screening of compound sets of unprecedented size in a cost-efficient fashion. Encoded libraries enable a physical connection between a phenotype (i.e., a ligand) and the corresponding genetic information.

Philochem has been practicing antibody-phage display technology for the last 25 years. All antibody-ligands, that Philochem has moved to clinical trials, stem from research activities which have been conducted using its proprietary libraries.

In 2004, our group pioneered the construction of DNA-encoded combinatorial libraries of organic molecules. The technology allows the rapid selection of specific binders (“Phenotype”), physically connected to unique DNA tags (“Genotype”) that work as amplifiable identification barcodes. Since then, Philochem has synthesized several DNA-encoded chemical libraries, featuring different designs, that have yielded high affinity and selective binders to a variety of target proteins of pharmaceutical interest.

To date, Philochem uses encoded libraries for both in house discover programs and in the frame of collaborations with pharmaceutical industrial or academic partners.


Puglioli et al. (2022) Chem, doi: 10.1016/j.chempr.2022.10.006

Dakhel et al. (2022) ChemMedChem, 17, e202200350

Bassi et al. (2021) J Med Chem, 64, 15799-15809

Oehler et al. (2021) Chemistry, 27, 8985-8993

Favalli et al. (2021) Nat Chem, 13, 540-548

Gironda-Martinez et al. (2021) J Med Chem  64, 17496-17510

Bassi et al. (2020) Advanced Science, 7(22): 2001970

Prati et al. (2020) Biochem Biopsy’s Res Commun, 533, 235-240

Lerner and Neri (2020) Biochem Biopsy’s Res Commun, 527, 757-759

Sannino et al. (2019) Chembiochem, 20, 955-962

Li et al. (2018) Nat Chem, 10, 441-8

Dal Corso et al. (2018) Agew Chem Int Ed Engl, 57, 17178-82

Neri and Lerner (2018) Annu Rev Biochem, 8, 479-502

Bigatti et al. (2017) ChemMedChem 12,1748

Li et al. (2016)  ACS Comb Sci, 18, 438-43

Franzini et al. (2015) Anger Chem Int Ed Engl, 23, 3927-31

Scheuermann et al. (2015) Curr Open Chem Viol, 26, 99-103

Scheuermann et al. (2010) Chembiochem 11, 931-7

Mannocci et al. (2008) Proc Natl Acad Sci USA, 105, 17670-5

Melkko et al. (2004), Nature Biotechnol, 22-568-74

2. Discovery and validation of pharmaceutical targets


The development of targeted therapeutics crucially relies on the identification of target antigens, which are specifically expressed at the site of disease, and which are readily accessible for agents coming from the bloodstream.

In collaboration with with ETH Zürich, Philochem has pioneered chemical proteomics methods for the characterization of accessible markers of pathology, which can be drugged by antibodies and small molecule ligands.

In a simple setup, cell lines can be submitted to surface biotinylation followed by capture on streptavidin resin and mass spectrometric analysis of tryptic peptides.

In a more complex setup, in vivo biotinylation procedures of rodent models of pathology enable the chemical proteomic characterization of vascular proteins in health and in disease. The technology has been extended to the ex vivo perfusion of surgically-resected human organs with cancer.

More broadly, we use MS-based chemical proteomics approaches to study the mechanism of action of our drugs. This includes the mass spectrometric quantification of drug delivery and release, as well as MHC-I peptidome analysis


Mass Spectrometry-Based Method for the Determination of the Biodistribution of Tumor-Targeting Small Molecule–Metal Conjugates
Gilardoni et al. (2022) Anal Chem, 93, 10715

Probst et al. (2017) Cancer Res, 77, 3644-54

Ritz et al. (2017) Proteomics, 17, 10.1002/pmic.201600364

Gloger et al. (2016) Cancer Immunol Immunother, 65, 1377-93

Ritz et al. (2016) Proteomics, 16, 1570-80

Sofron et al. (2016) Eur J Immunol, 46, 319-28

Elia et al. (2014) J Proteomics, 107, 50-5

Neri and Supuran (2011) Nat Rev Drug Discov, 10, 767-77

Fugmann et al. (2011) Kidney Int, 80, 272-81

Roesli et al. (2011) J Proteomics, 74, 539-46

Schliemann et al. (2010) Blood, 115, 736-44

Borgia et al. (2010) Cancer Res, 70, 309-18

Fugmann et al. (2010) Proteomics, 10, 2631-43

Rösli et al. (2008) Methods Mol Biol, 418, 89-100

Conrotto et al. (2008) Int J Cancer, 123, 2856-64

Castronovo et al. (2006) Mol Cell Proteomics, 5, 2083-91

Brack et al. (2006) Clin Cancer Res, 12, 3200-8

Scheurer et al. (2005) Proteomics, 5,2718-28

Rybak et al. (2005) Nat Methods, 2, 291-98

Neri and Bicknell (2005) Nat Rev Cancer, 5,436-46

Small Molecule Therapeutics


Low molecular weight compounds represent attractive alternatives to antibodies for tumor targeting applications. The advantages of small molecule therapeutics include a fast extravasation, a deep and homogeneous penetration into solid tumors, as well as faster development timelines.

Thanks to technological advances in the field of DNA-encoded chemical libraries, we are able to generate small molecule ligands with antibody-like properties featuring ultra-high affinity to their target antigen and long residence time at the tumor site.

Philochem uses small ligands with exceptional targeting performance for the selective delivery of (i) radionuclides, (ii) cytotoxic agents, (ii) immunomodulators, or (iv) adaptors for universal Chimeric Antigen Receptor T cell therapy.

Please visit our pipeline section for more information about individual programs.


Puglioli et al. (2022) Chem, doi: 10.1016/j.chempr.2022.10.006

Zana et al. (2022), Clin Cancer Res CCR-22-1788

Lucaroni et al. (2022)  Eur J Nucl Med Mol Imaging, doi: 10.1007/s00259-022-05982-8

Galbiati et al. (2022) J Nucl Med, numed.122.264036

Backhaus et al. (2021) Eur J Nucl Med Mol Imaging, 10.21203/

Millul et al. (2021) PNAS, 118, 16, e2101852118

Immunotherapy with Immunocytokines and PD-1 Blockade Enhances the Anticancer Activity of Small Molecule-Drug Conjugates Targeting Carbonic Anhydrase IX

Millul et al. (2021) Mol Cancer Ther, 20, 512-22

Kulterer et al. (2021) J Nucl Med, 62, 360-5

Pellegrino et al. (2020) Bioconjug Chem, 31, 1775-83

Cazzamalli et al. (2018) Clin Cancer Res, 24, 3656-67

Cazzamalli et al. (2018) JACS, 140, 1617-21

Cazzamalli et al. (2017) J Control Release, 246, 39-45

Cazzamalli et al. (2016) Mol Cancer Ther, 15, 2926-35

Krall et al. (2016) J Nucl Med, 57, 943-9

Wichert et al. (2015) Nat Chem, 7, 241-9

Casi & Neri (2015) J Med Chem, 58, 8751-61

Minn et al. (2016) Oncotarget, 7, 56471-79

Yang et al. (2015) Oncotarget, 6, 33733-42

Krall et al. (2014) Chem Sci, 5, 3640-4

Krall et al. (2014) Angew Chem Int Ed, 53, 4231-5

Krall et al. (2013) Angew Chem Int Ed Engl, 52, 1384-1402

Müller et al. (2013) J Nucl Med, 54, 124-31

Ahlskog et al. (2009) Bioorg Med Chem Lett, 19, 4581-6

Dumelin et al. (2008) Angew Chem Int Ed Engl, 47, 3196-3201