DNA-Encoded Library (DEL) Glossary

DEL Fundamentals

DNA-encoded library (DEL)

A collection of small molecules, each permanently linked to a unique DNA barcode that records its chemical structure. Barcoding lets every member of a library containing millions to billions of distinct compounds be screened together in one pooled reaction, with the winners identified afterward by sequencing rather than by testing each compound individually.

Split-pool synthesis

The standard method for building a DEL: a pool of DNA-tagged intermediates is split into subsets, each subset reacts with a different chemical building block and receives a corresponding DNA tag recording that step, and the subsets are pooled again before the next split. Repeating this for several cycles generates a combinatorial library whose size grows multiplicatively with each additional cycle.

Building block (BB)

One of the chemical reagents combined at each synthesis cycle to construct library members. A library’s diversity is largely a function of how many distinct building blocks are available at each cycle and how compatible they are with DNA-linked, aqueous-phase chemistry.

DNA barcode (genetic tag)

The short DNA sequence attached to a library member that uniquely identifies the synthetic steps, and therefore the chemical structure, used to build it. Barcodes are read by PCR amplification and sequencing after selection to identify which compounds were enriched.

On-DNA / off-DNA

"On-DNA" describes a compound still attached to its DNA barcode, as it exists during library synthesis and selection. "Off-DNA" describes the same compound resynthesized without the barcode, which is required before any conventional biochemical, biophysical, or cellular assay can test it directly.

Selection

The core DEL experiment: exposing the library to a target (purified protein, immobilized protein, or a target expressed in a living cell) under conditions that allow binders to be physically separated from non-binders, so that binding library members become relatively more abundant in the recovered DNA pool.

Enrichment

The relative increase in a library member’s sequencing read count after selection compared to its abundance in the starting (unselected) library. Enrichment is a proxy for binding, not a direct measurement of affinity, and is only a hypothesis until the compound is resynthesized off-DNA and tested directly.

Counter-selection

A parallel or sequential selection run against a related but undesired target (e.g., a closely related protein family member, or the DNA tag/matrix itself) to identify and remove library members that bind nonspecifically rather than to the intended target.

Decoding

The process of determining which compounds were enriched by PCR-amplifying and sequencing the DNA barcodes recovered after selection, then computationally translating barcode sequences back into the chemical structures they encode.

DNA-encoded chemical library (DECL)

A synonym for DNA-encoded library, used interchangeably in the literature and in some older publications. Both terms describe the same thing: a pooled collection of small molecules each carrying a DNA barcode that records its structure.

Encoded library technology (ELT)

An umbrella term for the family of methods that attach amplifiable DNA information to synthetic small molecules so that large collections can be screened by affinity selection and read out by sequencing. DEL synthesis and DEL selection are both components of encoded library technology.

DNA-compatible chemistry

Chemical reactions that proceed in the dilute, aqueous, near-neutral conditions a DNA barcode tolerates without depurination, strand cleavage or loss of amplifiability. The set of usable reactions is narrower than in conventional medicinal chemistry, and expanding it is one of the field’s main areas of methodological work.

Truncate (truncated product)

A library member whose DNA barcode records a synthetic step that did not actually occur on the small molecule, leaving an incomplete structure attached to a complete code. Truncates arise when DNA tagging is independent of chemical conversion, and they are a principal source of false positives because the compound resynthesized from the barcode is not the compound that bound.

Library size

The number of distinct compounds in a DEL, commonly between a few million and several billion. Size alone is a weak quality measure: diversity, physicochemical property distribution, barcode fidelity and off-DNA resynthesizability determine how many library members can actually yield a tractable hit.

Chemical diversity

How broadly a library samples chemical space — in scaffold topology, functional groups, three-dimensional shape and stereochemistry — rather than how many members it contains. Diversity is set largely by building block selection and by how many positions are varied per cycle.

Vipergen Technology & Platforms

YoctoReactor (yR)

Vipergen’s DEL synthesis platform, which assembles DNA-encoded small molecules using self-assembling, complementary DNA junctions to bring chemical building blocks into reactive proximity. Purification using the DNA itself as a handle after each chemical step is designed to eliminate truncated or incompletely reacted intermediates, so that each DNA barcode corresponds to one defined, fully synthesized compound.

Binder Trap Enrichment (BTE)

Vipergen’s in vitro, homogeneous (solution-phase) DEL selection method. Rather than immobilizing the target on a bead, BTE lets the library and a DNA-tagged target reach binding equilibrium in solution, uses high-factor dilution to shift the system into dissociation-dominated kinetics, then emulsifies the mixture into water-in-oil droplets so that genuine binding pairs can be isolated and their DNA tags ligated together for later sequencing.

Cellular Binder Trap Enrichment (cBTE)

Vipergen’s in vivo DEL selection method, in which the target protein is expressed from injected mRNA inside a living cell (a Xenopus laevis oocyte) and the DEL is selected against it intracellularly, without ever purifying the target outside the cell. Published in the Journal of the American Chemical Society (2021), validated to date on three targets: p38α, ACSS2, and DOCK5.

Bait

In BTE/cBTE selection, a DNA-tagged small molecule or binding moiety that attaches to the target protein, giving it a sequence-specific DNA identity so that library members binding near it can be captured and ligated to that identity during selection.

Prey

A fusion tag expressed together with the target protein (e.g., in cBTE) that the bait molecule recognizes, establishing the DNA-taggable link between the target and the Binder Trap Enrichment chemistry.

Dissociation-dominated kinetics

A state obtained during selection, used in BTE, in which the system is diluted enough that bound complexes are governed primarily by their off-rate (how slowly they dissociate) rather than by rebinding. This allows selection to discriminate binders by residence time rather than by binding event frequency alone.

Residence time

How long a bound complex persists before dissociating. Selection methods that rely on wash steps systematically favor compounds with longer residence time, independent of their equilibrium affinity (Kd).

Xenopus laevis oocyte

A large (roughly 1 mm diameter) frog egg cell long used in electrophysiology and receptor pharmacology as a heterologous expression system, because it folds, traffics, and functionally supports complex human proteins, including membrane proteins, with reasonable fidelity after mRNA injection. It is the cell type Vipergen’s cBTE selection is performed in.

Microinjection

The technique of injecting mRNA, DNA-tagged bait, and DEL library directly into an individual oocyte, used to deliver all the components cBTE selection requires into the same living cell.

Selection Formats & Target Classes

Affinity-bead (immobilized-target) selection

The classical DEL selection format: the target protein is immobilized on a solid support (typically streptavidin or magnetic beads), the library is incubated with it, and unbound material is washed away before recovering binders. It is the most widely used and longest-established DEL selection format, but it requires a purified, immobilizable (usually soluble or truncated) form of the target.

Homogeneous selection

A selection format in which target and library are mixed freely in solution rather than with the target bound to a surface. Vipergen’s BTE is a homogeneous, in vitro method.

Cell-based selection

DEL selection performed against a target expressed inside or on a living cell rather than purified outside one. Published methods include cell-surface selection (library incubated directly with intact cells) and intracellular selection such as Vipergen’s cBTE; the category exists specifically to reach targets that resist purification in active form.

Affinity selection

The general principle underlying DEL screening: the library is exposed to a target and library members are partitioned by their affinity for it, with bound members physically recovered and identified. The term covers immobilized, homogeneous and cell-based formats alike.

Panning

A term borrowed from phage display for an iterative cycle of binding, washing and recovery, sometimes applied to multi-round DEL selections. The analogy is imperfect: DEL members cannot be amplified and re-displayed the way a phage particle can, so only the barcode is amplified between rounds.

False positive

A library member that appears enriched after selection but does not bind the target when resynthesized and tested off-DNA. Common causes are truncates, binding to the matrix or the DNA rather than the target, PCR and sequencing artifacts, and aggregation.

Hit rate

The proportion of selected and resynthesized library members that confirm as genuine binders in an orthogonal off-DNA assay. Hit rate is a property of the library, the selection format and the target together, and is more informative about platform quality than raw enrichment values.

Next-generation sequencing (NGS)

High-throughput parallel DNA sequencing, used after selection to count how many times each barcode was recovered. NGS read counts are the raw quantitative output of a DEL screen.

Read count

The number of times a given barcode is observed in sequencing output. Read counts are compared against the compound’s abundance in the unselected library, and against a statistical background model, to decide whether an apparent enrichment is meaningful.

Multiplexed selection

Running one library against several targets, or against a target plus related anti-targets, in the same experiment. Multiplexing yields comparative selectivity data from a single screen rather than requiring a separate campaign per protein.

Expression (feasibility) study

A preparatory experiment, used ahead of cell-based selection, confirming that the target protein is expressed, folded and accessible in the chosen cell system before library material is committed. It replaces the protein production and purification step that in vitro selection requires.

GPCR (G protein-coupled receptor)

A large family of integral membrane receptors whose signaling-relevant conformations typically depend on their native lipid bilayer environment, making them difficult to study once extracted and purified with detergent — a frequently cited rationale for cell-based DEL selection.

Ion channel

A multi-pass membrane protein that forms a pore regulating ion flow across a cell membrane. Like GPCRs, ion channels are a drug target class for which purified, immobilized preparations often fail to preserve the conformations relevant to drug binding.

Integral membrane protein

A protein permanently embedded in a lipid membrane (as opposed to a soluble, extracellular, or peripherally-associated protein). This category, which includes GPCRs and ion channels, is the target class most often cited as the dividing line between affinity-bead and cell-based DEL selection.

Protein-protein interaction (PPI)

A binding interaction between two proteins, often targeted in DEL campaigns either to find a small molecule that blocks the interaction (a PPI inhibitor) or that stabilizes it (a molecular glue).

Soluble target

A protein that is stable, folds correctly, and remains active once purified away from a cell — the target type affinity-bead and homogeneous selection handle well, including most enzymes and many protein-protein interaction pairs.

Target immobilization

The step, specific to bead-based selection, of chemically attaching a purified target protein to a solid support (commonly via a His-tag or biotin handle) so the library can be washed over it. Immobilization is a documented source of selection artifacts, including tag-induced misfolding and steric occlusion of the target’s binding face.

Transcription factor (TF)

A protein that binds specific DNA sequences to control gene transcription. Transcription factors are frequently cited as hard-to-drug because they typically act through broad protein-protein and protein-DNA interfaces and contain disordered regions rather than enzyme-like pockets, although approved drugs and clinical candidates against several now exist.

DNA-binding protein

Any protein whose function involves binding DNA, including transcription factors, polymerases, repair enzymes and chromatin-associated proteins. As a screening category the shared difficulty is that a DNA-barcoded library can be captured nonspecifically by a nucleic-acid-binding surface, which selection conditions must control for.

Intrinsically disordered protein (IDP)

A protein that does not adopt a single stable three-dimensional structure under physiological conditions, existing instead as an ensemble of interconverting conformations. Disorder is often functional, allowing one protein to recognize several partners and respond quickly to cellular signals.

Intrinsically disordered region (IDR)

A disordered segment within an otherwise structured protein. IDRs commonly mediate cofactor recruitment, post-translational regulation and assembly, and are frequent in transcription factors and signaling scaffolds.

Conformational ensemble

The population of distinct conformations a flexible protein samples at equilibrium. Ligands acting on disordered targets are generally understood to shift the balance within this population rather than to occupy one fixed pocket.

Biomolecular condensate

A membraneless cellular compartment formed when proteins and nucleic acids, often disorder-rich, demix into a distinct phase through multivalent interactions. Because local concentration and dynamics inside a condensate differ from dilute solution, a compound’s effect there may not be predicted by a conventional binding assay.

Cryptic pocket

A binding site that is not visible in a protein’s unbound structure but opens transiently, or forms upon ligand binding. Cryptic pockets explain why interfaces that look featureless in a single structure can still prove ligandable.

Hotspot

A small cluster of residues contributing a disproportionate share of the binding energy at a protein-protein interface. Hotspots are why a molecule far smaller than the buried interface area can still disrupt an interaction, and they are the usual anchor point for inhibitor design.

Orthosteric and allosteric

Orthosteric describes a ligand binding at the functional site itself, competing directly with the natural partner or substrate. Allosteric describes a ligand binding elsewhere and changing activity indirectly, which can offer selectivity or partial modulation where the functional site is too flat or too conserved.

Protein-protein interaction stabilizer

A compound that strengthens or locks an existing protein-protein interaction rather than disrupting it. Stabilization is therapeutically useful where the disease state involves loss of a complex or where holding a complex in an unproductive state is the desired outcome; molecular glues are the induced-proximity case of the same principle.

Kinase

An enzyme that transfers a phosphate group from ATP to a substrate protein. Kinases are among the most tractable small-molecule target classes because of their defined ATP-binding pocket, and they are commonly used as benchmark targets for new screening platforms.

Nuclear receptor

A ligand-regulated transcription factor family, including the androgen and estrogen receptors, that binds small-molecule ligands directly and then acts on DNA. Nuclear receptors are both a validated drug target class and a transcription factor class, and so sit between conventional and hard-to-drug categories.

Molecular Glues & Induced-Proximity Modalities

Targeted protein degradation (TPD)

A therapeutic strategy that removes a disease-associated protein from the cell by recruiting it to the cell’s own degradation machinery, rather than blocking its activity. Because the effect is catalytic, TPD can act on proteins that lack a functional site to inhibit, including scaffolding proteins and transcription factors.

Induced proximity

The deliberate forcing of an interaction between two proteins that would not normally associate, in order to produce a biological effect. Degradation is the most developed application, but the same principle is used to recruit deubiquitinases, kinases, autophagy machinery and nucleases.

Molecular glue

A small, monovalent compound that induces or stabilizes an interaction between two proteins, forming a ternary complex. Most reported glues recruit a target protein to an E3 ubiquitin ligase and cause its degradation, but the mechanism also covers stabilizing a beneficial complex or holding one in an inactive state.

E3 ubiquitin ligase

The enzyme that confers substrate specificity in the ubiquitin-proteasome system by transferring ubiquitin to a target protein. More than 600 are encoded in the human genome; only a small number have so far been exploited pharmacologically, which is why discovering ligands for new ones is an active area.

Cereblon (CRBN)

The substrate receptor of a cullin-RING E3 ligase complex, and the most clinically validated molecular glue target. Thalidomide and its analogues bind cereblon and reprogram its substrate preference, redirecting it onto proteins it would not otherwise degrade.

Von Hippel-Lindau (VHL)

A substrate recognition component of an E3 ubiquitin ligase complex, and with cereblon one of the two E3 handles most widely used in heterobifunctional degrader design. Ligands that bind VHL serve as the E3-recruiting end of a PROTAC.

Immunomodulatory imide drug (IMiD)

The drug class comprising thalidomide, lenalidomide and pomalidomide. Approved and in clinical use for years before their mechanism was understood, IMiDs were retrospectively shown to act as molecular glues that recruit transcription factors to cereblon for degradation.

Degron

A structural feature in a protein that marks it for degradation by targeting it to a specific E3 ligase. Molecular glues can work by presenting or mimicking a degron, creating a recognition signal on a protein that did not previously carry one.

Ternary complex

The three-component assembly of target protein, compound and recruited protein that induced-proximity drugs must form to work. Its formation, geometry and lifetime, rather than the compound’s affinity for either protein alone, usually determine whether degradation occurs.

Cooperativity

Whether the presence of one protein makes the compound bind the other more tightly, measured as the ratio of ternary to binary affinity. Positive cooperativity indicates favorable protein-protein contacts in the complex and is often a better predictor of degradation efficiency than binary binding data.

Ubiquitin-proteasome system (UPS)

The main cellular pathway for disposing of short-lived and misfolded soluble proteins, in which a chain of ubiquitin molecules is attached to a substrate and the tagged protein is degraded by the 26S proteasome. Most targeted degraders operate through this pathway.

PROTAC (proteolysis-targeting chimera)

A bifunctional molecule with a ligand for the target protein, a ligand for an E3 ubiquitin ligase, and a linker joining them. By binding both simultaneously it forces a ternary complex and drives ubiquitination and degradation of the target.

Heterobifunctional molecule

Any compound built from two distinct binding ligands joined by a linker, each engaging a different protein. PROTACs are the best-known example; the architecture underlies most of the proximity-inducing modalities named below.

Degrader linker

The chemical tether joining the two ligands of a heterobifunctional degrader. Its length, rigidity and attachment geometry determine whether a productive ternary complex can form, and linker optimization is usually a major part of degrader medicinal chemistry. DEL-derived hits carry an inherent advantage here, because the position where the compound was attached to its DNA barcode indicates a vector known to tolerate substitution.

Hook effect

The loss of activity seen at high concentrations of a bifunctional degrader, where the compound saturates the target and the E3 ligase separately in two binary complexes instead of bridging them into one ternary complex. Monovalent molecular glues do not show this behaviour.

Occupancy-driven and event-driven pharmacology

Occupancy-driven describes a conventional inhibitor, which must remain bound to sustain its effect. Event-driven describes a degrader, which triggers an irreversible outcome and can then dissociate and act again, so sustained high exposure is less critical.

Targeted protein stabilization

The inverse of targeted degradation: deliberately preventing a protein’s destruction to raise its cellular level. Relevant where disease arises from insufficient protein, such as loss of a tumour suppressor or a degradation-prone variant.

DUBTAC (deubiquitinase-targeting chimera)

A bifunctional molecule that recruits a deubiquitinase to a ubiquitinated target, removing its ubiquitin chains and rescuing it from degradation. The mechanism achieves targeted protein stabilization without globally inhibiting E3 ligase activity.

RIPTAC (regulated induced proximity targeting chimera)

A bifunctional molecule that binds a broadly expressed essential protein and a tumour-restricted protein at the same time, functionally disabling the essential protein only in cells that express both. The result resembles synthetic lethality without requiring a directly druggable mutation.

LYTAC (lysosome-targeting chimera)

A conjugate that routes an extracellular or cell-surface protein to the lysosome for degradation by engaging a cell-surface trafficking receptor. LYTACs extend degradation to targets the proteasome cannot reach.

ATTEC (autophagosome-tethering compound)

A small molecule that tethers a target directly to a component of the autophagy machinery, delivering it to the autophagosome. Because it acts without ubiquitination, the approach can address aggregates and organelles.

AUTAC (autophagy-targeting chimera)

A bifunctional molecule carrying a degradation tag that marks its target for selective autophagy. Reported applications include degradation of protein aggregates and of damaged mitochondria.

AUTOTAC (autophagy-targeting chimera, p62-mediated)

A bifunctional molecule that recruits a target to the autophagy receptor p62, driving its delivery to the autophagy-lysosome pathway.

RIBOTAC (ribonuclease-targeting chimera)

A bifunctional molecule that recruits a cellular ribonuclease to a specific RNA, causing that RNA to be cleaved. It applies induced-proximity logic to RNA rather than protein targets.

ULKTAC (ULK1-targeting chimera)

A bifunctional molecule that recruits the autophagy-initiating kinase ULK1 to a target protein to trigger autophagic degradation.

PHICS (phosphorylation-inducing chimeric small molecule)

A bifunctional molecule that brings a kinase and a chosen substrate into proximity, causing the substrate to be phosphorylated. The outcome is a post-translational modification rather than degradation.

PHORC (phosphatase-recruiting chimera)

A bifunctional molecule that recruits a phosphatase to a phosphorylated target to drive its dephosphorylation, the converse of a phosphorylation-inducing chimera.

Photoswitchable and photocaged degraders (PHOTAC, pcPROTAC)

Degraders designed to be activated by light. Photoswitchable versions toggle reversibly between active and inactive forms under different wavelengths; photocaged versions are irreversibly unmasked when a blocking group is cleaved by light, giving spatial and temporal control.

Hit Validation & Medicinal Chemistry Terms

Off-DNA resynthesis

Chemically resynthesizing an enriched DEL hit without its DNA barcode, so it can be tested in conventional assays. Enrichment data alone is a hypothesis; resynthesis and confirmatory testing are what turn it into a validated hit.

SAR (structure-activity relationship)

The pattern linking small changes in a compound’s chemical structure to changes in its measured potency or activity. SAR data from close structural analogs within a DEL hit cluster is often used as early evidence that a hit’s activity is real and structurally specific rather than an assay artifact.

SPR (surface plasmon resonance)

A label-free biophysical technique used to directly measure the binding affinity and kinetics (on-rate, off-rate) of an off-DNA resynthesized hit against its target.

ITC (isothermal titration calorimetry)

A biophysical technique that measures the heat released or absorbed during binding, used to directly confirm and thermodynamically characterize an off-DNA hit’s interaction with its target.

CETSA (cellular thermal shift assay)

An assay that measures a target protein’s thermal stability shift upon ligand binding inside intact cells, used to confirm that a hit engages its target in a cellular (not just biochemical) context.

FP (fluorescence polarization)

A solution-based binding assay that measures changes in the rotational speed of a fluorescently labeled molecule upon binding, commonly used as an orthogonal confirmation assay for off-DNA DEL hits.

Rule of Five (Ro5)

Lipinski’s set of simple physicochemical guidelines (molecular weight, hydrogen bond donors/acceptors, cLogP, each kept below set thresholds) associated with orally druglike small molecules. Used as one benchmark for assessing a DEL library’s or hit’s drug-likeness.

cLogP

A calculated measure of a compound’s lipophilicity (its predicted partition between octanol and water). One of the Rule of Five properties and a common library-composition statistic.

Fsp3

The fraction of a molecule’s carbon atoms that are sp3-hybridized (three-dimensional rather than flat/aromatic). Higher Fsp3 is generally associated with better clinical-stage success rates and is a common library-quality statistic.

Tanimoto similarity

A standard numerical measure (0 to 1) of chemical structural similarity between two molecules, used to assess library diversity and to cluster DEL hits into structurally related families.

Hit-to-lead

The drug discovery stage following hit confirmation, in which a validated hit series is chemically optimized for potency, selectivity, and drug-like properties before advancing toward lead candidate status.

Hit identification (Hit ID)

The first stage of small-molecule discovery, in which large compound collections are narrowed to a small set of structurally diverse compounds with confirmed, reproducible activity suitable for optimization. DEL screening is one of several hit identification methods, alongside high-throughput, virtual, fragment-based and phenotypic screening.

Lead

A confirmed hit that has been optimized to meet stricter thresholds for potency, selectivity, metabolic and physicochemical properties, and synthetic tractability, sufficient to justify preclinical investment. The distinction from a hit is one of degree and of evidence, not of chemical class.

High-throughput screening (HTS)

Testing a plated compound library one compound per well against a biological target, using automation and a biochemical or cellular readout. HTS measures activity directly but requires an assay to be developed, and library sizes are typically hundreds of thousands to a few million.

Virtual screening

Computational triage of compound collections before any physical testing, using structure-based docking, ligand-based pharmacophore models or machine-learned scoring. It can rank very large enumerated spaces cheaply but depends on the quality of the target structure and the scoring function.

Fragment-based screening (FBS)

Screening low-molecular-weight fragments at relatively high concentrations using sensitive biophysical readouts, then growing, merging or linking the fragments into larger compounds. Hit rates are high and binding is weak, so structural information is usually needed to guide elaboration.

Phenotypic screening

Screening in a cellular or organismal assay that measures an observable outcome without presupposing a molecular target. It captures cellular context and can find first-in-class mechanisms, at the cost of requiring subsequent target deconvolution.

Rule of Three (Ro3)

A set of property guidelines for fragment libraries, generally molecular weight below 300, cLogP of 3 or less, and no more than three hydrogen bond donors and acceptors. It is the fragment-screening counterpart to the Rule of Five.

PAINS (pan-assay interference compounds)

Structural motifs known to produce apparent activity across unrelated assays through mechanisms such as redox cycling, covalent reactivity, chelation or aggregation. Hits matching a PAINS motif are flagged for extra scrutiny rather than automatically discarded.

Z-factor

A statistic describing how well an assay separates its positive and negative controls relative to their variability, used to decide whether an assay is robust enough to screen. Values above 0.5 are conventionally considered acceptable.

IC50 and EC50

The concentration producing half-maximal inhibition, or half-maximal effect, in a given assay. Both are assay-dependent and so are used for ranking compounds and tracking structure-activity relationships rather than as absolute constants.

KD (dissociation constant)

The equilibrium constant describing the affinity of a binding interaction, measured by biophysical methods such as surface plasmon resonance or isothermal titration calorimetry. Unlike IC50, it is a property of the interaction rather than of the assay format.

Ki (inhibition constant)

The equilibrium constant for an inhibitor binding its enzyme, derived from kinetic measurements. It is model-dependent but more closely tied to mechanism than an IC50.

BLI (bio-layer interferometry)

A label-free optical technique measuring binding kinetics in real time from interference changes at a sensor surface. Used alongside surface plasmon resonance for orthogonal confirmation of off-DNA hits.

DSF (differential scanning fluorimetry)

A thermal shift method that detects ligand binding from the change in a protein’s melting temperature. It is fast and consumes little material, which makes it useful for triaging a hit list before more demanding biophysics.

NanoBRET

A live-cell resonance energy transfer assay that measures whether a compound engages its target inside intact cells, and with what residence time. It addresses the gap between confirmed biochemical binding and cellular activity.

Orthogonal assay

An assay that tests the same conclusion by a physically different mechanism than the primary screen. Confirming a DEL hit in an orthogonal format is what distinguishes a genuine binder from a selection or sequencing artifact.

Emerging Approaches

Synthetic lethality

A relationship in which loss or inhibition of either of two genes is tolerated, but loss of both is lethal. In oncology it allows a tumour-specific genetic lesion to be exploited by drugging its partner, killing cancer cells while sparing normal tissue.

RNA-targeted small molecule

A compound that binds a structured RNA to alter its splicing, translation, stability or processing, rather than acting on a protein. Approaches include direct binders and recruitment of cellular nucleases.

Commercial & IP Terms

Confirmed hit

A library member that has been resynthesized off-DNA and shown to bind or act on the target in an orthogonal assay — distinct from a raw sequencing enrichment signal, which is a hypothesis rather than a confirmed result.

Barcode-to-compound fidelity

How reliably a DEL’s DNA barcode corresponds to the chemical structure it is meant to encode. Split-pool synthesis is vulnerable to truncated products and mis-encoding; fidelity is typically protected by purifying after each synthetic step to remove incompletely reacted intermediates before the next cycle.

Turnaround time (staged)

The calendar time a DEL screening engagement takes, broken into discrete stages (e.g., selection, sequencing/decoding, hit triage, off-DNA resynthesis, and confirmation), rather than a single headline number. (See also: How to Choose a DNA-Encoded Library Screening Partner: 7 Criteria.)