Protein Maps Reveal Hidden Drug Sites, Researchers Say

Researchers at the Wellcome Sanger Institute and the Centre for Genomic Regulation (CRG) in Barcelona have published protein maps of two major protein families, in a pair of papers in Nature Structural & Molecular Biology. The work is lab and cell results only. No drug has been developed from the maps, and a possibility that they could help design drugs with fewer side effects remains just that: a possibility.

The Sanger Institute set out the findings in a 12 November 2026 notice. CRG issued its own account a day earlier, on 11 November 2026 at 17:01 local time in Spain, or 16:01 GMT. Sanger says the research was supported by Wellcome. The two methods are called GPCR-MAPS and TF-MAPS.

Sanger says the papers “mark the beginning of a ‘new era’ of targeted drug discovery”. CRG uses different wording. In its account of the GPCR work, it describes an earlier first chapter of screening thousands of compounds with little understanding of why they worked, and a second chapter, from the 1990s, of designing drugs from a receptor’s three-dimensional structure, work that earned a Nobel Prize in 2012. CRG says the protein’s shape helped researchers understand where a drug can bind, but could not help predict what a drug will do once it binds. It says the new method enables a “third era”, in which scientists can understand both the structure and the function of every part of the receptor. That “third era” phrasing is CRG’s, not Sanger’s.

Maps of receptors that many existing drugs already target

Sanger says there are 800 different types of G protein-coupled receptors, or GPCRs, and that one in three regulatory-approved drugs worldwide targets this family of proteins. Adrenaline, histamine and serotonin all rely on different variants to transmit signals from the outside world into the cell, Sanger says, and the same family is also a target for beta blockers, antihistamines, opioids and asthma inhalers. The first study, led at CRG, focused on the beta-2 adrenergic receptor, the protein targeted by asthma and chronic obstructive pulmonary disease (COPD) inhalers such as salbutamol and salmeterol.

The team built the map by creating thousands of variants of the protein, swapping one building block for another. “They synthesised 7,500 versions in total, each of which was put into a human cell and tested with different drug doses and other parameters, producing more than 150,000 measurements for a single receptor,” Sanger says. The institute says the resulting data showed new potential drug targets that had been previously hidden from sight, and that many of the regions have adjustable positions that can be altered to fine-tune the behaviour of the receptor. To test whether the method works beyond a single receptor, the team applied it to a second protein involved in regulating water in the kidneys “and found comparable results.” CRG says the research team’s long-term ambition is to build similar maps for many more members of the GPCR family.

Dr Taylor Mighell, first author of the GPCR study at CRG, said: “You can have a perfect diagram of the working parts of a protein and still not know what happens when you change a component. Now, we have something closer to a manual than a diagram.”

Transcription factors treated as hard to drug

In the second study, Sanger scientists looked at transcription factors, or TFs, using TF-MAPS. “The human genome encodes more than 1,500 TFs,” Sanger says, “with variants known to cause hundreds of human genetic diseases.” The institute also says that “there are no licensed or experimental drugs against the vast majority of TFs that are implicated in human diseases.”

The team applied TF-MAPS to three transcription factors, HNF1A, FOXG1 and FOXP1, and “found that all three TFs have potentially druggable functional ‘pockets’.” Dr Xianghua (Cici) Li, first author of the TF study, formerly at the Wellcome Sanger Institute and now a lecturer at King’s College London, said: “Using TF-MAPS we have challenged the view that transcription factors are undruggable proteins.” Li also said the method is general, scalable and requires no specialist equipment, and that the team found functionally important drug-sized pockets in three TFs that cause diseases such as diabetes, cancer and rare neurodevelopmental disorders.

Professor Ben Lehner, lead author of both studies, Head of Generative Genomics at the Wellcome Sanger Institute and Senior Group Leader at CRG, said: “There are thousands of proteins that are important drug targets in human diseases that we have not yet been able to develop drugs for. By building complete maps of how these proteins function we can identify the best sites to target with drugs in each of these proteins. With these two new methods we can now do this for hundreds of the most important proteins for human biology and drug discovery.”

Sanger says the protein maps “could help design new treatments, and drugs with fewer side effects, for a wide range of conditions, from heart disease to diabetes and cancer.” That is a prospect the institutes describe, not a result of the two papers. No medicine has been taken into patients on the back of these maps.

The work sits alongside other research TSN has covered on how proteins and DNA can be mapped or targeted, including the Baker Lab’s AI-designed enzymes that cut specific proteins, a DNA nanoswitch platform used to screen protein-protein interaction drug leads, and DeepMind’s AlphaGenome 2, which predicts DNA effects in different cell types. Those projects, like this one, are still a long way from a finished medicine.

Analysis

The two papers give researchers a denser picture of where two important protein families can be poked, and of what happens when those sites change. That is a laboratory and cell-culture result. It is not a clinical result, and it is not a drug.

Lehner’s claim that the methods can now be applied to hundreds of important proteins is a statement about reach, not about a pipeline of new medicines. The kidney-receptor test is presented as a check that GPCR-MAPS can travel beyond one well-known asthma target. It is still a single extra protein, not a library of approved treatments.

The “drugs with fewer side effects” line is easy to over-read. Sanger presents it as something the maps could help design, not as something already shown in people, or even in an animal study reported here. The same caution applies to CRG’s “third era” framing. It is a useful way of placing the work after earlier periods of compound screening and structure-based design, but it is CRG’s wording, and it does not mean a new class of medicines has arrived. Sanger’s “new era” line should be read the same way: as the institute’s description of a shift in method, not as evidence that a treatment is ready.

For readers watching precision medicine, the useful fact is narrower and still substantial: two scalable mapping methods have been published, they have been applied to a handful of well-chosen proteins, and they have pointed to hidden or “potentially druggable” sites. Li’s point that TF-MAPS needs no specialist equipment may matter for how widely other labs can try the approach. Whether those sites can be turned into safer drugs is work that has not yet been done.

Sanger and CRG Map Hidden Drug Sites on Two Protein Families

Maps of receptors that many existing drugs already target

Transcription factors treated as hard to drug

Analysis

Sources

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