Q&A – Targeted Protein Degradation (PROTAC) for Drug Discovery

Yue Xiong, Cullgen

Q: Are PTOTAC soluble or insoluble?
A: Yes, PROTAC can be made soluble.

Q: You mentioned not knowing where to target in E3 ligases, why is targeting the substrate and E3 ligase interaction domain not plausible?
A: Yes, it is possible to develop E3 ligand by targeting the substrate-ligase interaction. In fact, that is how VHL ligand was developed. This is one consideration we discussed in our recent review article.

Q: Is there a reason why HECT E3 ligases are not considered in PROTAC design?
A: No specific reason as to why HECT ligases can’t be developed for PROTAC. One reason this has not happened yet may be that HECT are very large proteins and are not studied as well as CRL or other RING-type E3.

Q: Do you think the major challenge of lack of typical active pockets for CRLs being a large multi-unit protein family without typical active pockets to facilitate the drug design?
A: Yes, one major challenge to target/inhibit CRL is the lack of a well-defined active site, even though they act as an enzyme, like other enzymes such as kinases. But one could still target them by other means such as PPI inhibitor, albeit technically more challenging.

Q: How to understand the relationship between degradation activity, selectivity and possible off-target effects based on different targets, different cell lines, and different animal models?
A: I am afraid this is a $1M question and involves multiple aspects and I can’t responded with a simple answer. If you are asking for the selectivity, this is an advantage for the PROTAC since one could gain the view of selectivity of a given degrader at proteome scale by a simple proteomic analysis, which would be much more feasible than finding out how many kinases are affected by a given inhibitor.

Q: Do you think the Post translational modification of the E3 ligase complex is an important factor to be consider when designing PROTAC? Since PTM like Nedd will change the Cul flexibility and conformation. And how can we study this?
A: Neddylation is critically important for the activity of any CRL-based PROTAC. Other PTM such as phosphorylation, acetylation, methylation, so far do not seem to play critical role in the regulation of CRL as needylation.

Q: Did you test in any thermal assays of pain (got plate, tail flick etc.)?
A: No, we have not tested yet, but we do not have any reason to think that TRK degrader would not work for thermal pain.

Q: How to establish a scientific and credible PK/PD evaluation system as traditional methods cannot accurately assess the PK and PD properties of PROTACs?
A: There is no fundamental difference between PROTAC and traditional small molecule drugs when optimizing the PK, PD properties, although PROTAC molecules are larger, tend to be more unstable, have more hot-spots to be fixed and need more efforts to make into orally active.

Q: What are the advantages and disadvantages of N-degron pathway, over currently available E3 ligands.
A: Very little study on the feasibility of N-degron E3 for PROTAC at present. It’s difficult to comment, but I wonder whether high degree of substrate selectivity (specific amino acid sequences at particular location in the substrate protein) might be somewhat less compatible with the need of high degree of flexibility of PROTAC to target ‘any’ given proteins.

Q: This is a new area for me, so please excuse the basic question: what is the evidence that PROTACs (warhead-linker-E3 binder) small molecule is not subject to metabolism or degradation inside cells, and thus can be recycled?
A: PROTAC molecules ARE subjected to the intracellular metabolism and degradation. In fact, improving the metabolic stability of PROTAC is a major aspect of PROTAC medicinal pharmacology. The evidences supporting the recycling of degrader include the high potency, lasting effect and rapid kinetics.

Q: How to quickly and effectively screen for target protein ligands that can be used in PROTACs, especially those targeting protein−protein interactions
A: There are multiple ways to screen small molecule ligands/binders for proteins, but those binders are not very useful if not functional, until now. But there is no effective way right now to screen these initial binder-hits for their suitability as ligands for PROTAC. Such an assay, if developed, would be very useful for the TPD industry.

Q: What needs to happen before PROTACs, and molecular glues become a standard/accepted treatment?
A: Good phase 3 results, especially the ones that target a previously undruggable disease-causing protein.

Q: I believe PROTAC will decompose in few hours. So why we call it as catalytic?
A: We call the degrader catalytic because it connects an enzyme (E3 ligase) to a substrate and promotes a catalytic reaction (ubiquitylation). We don’t call the degrader catalyst, though. Yes, the degraders will be eventually decomposed, like the enzymes will be eventually degraded.

Q: For the TRK study, did you use a focused library to identify the degraders?
A: We discovered TRK degrader by linking and testing existing TRK ligands to a E3 ligand. This led to the discovery of potent degrader and we did not need to screen any library.

Q: What are your thoughts on the ADME optimization of PROTAC molecules for orally bioavailable drugs, since your company is optimizing their degraders?
A: Optimizing PROTAC into orally active compounds is not as challenging as a year or two ago. Although not routing yet, we have developed multiple orally active degraders targeting different proteins now.

Q: After targets ubiquitinated, they are always degraded by proteasome or they can be degraded by other mechanism, for example, autophagy?
A: Ubiquitin also tags proteins for lysosomal degradation, not just proteasome. This can be determined simply by using inhibitor specific to proteasome, lysosome or autophagy.

Q: Do you have any comments on the target selection for PROTAC drug discovery, for example, to differentiate from well-established inhibitors?
A: We think the future of PROTAC is to target previously undruggable non-enzyme proteins, not to compete with inhibitors.

Q: What do you think of slow vs. fast degrader? Would you go after slow degraders? (E.g. a degrader that start degrading the substrate after 20h)
A: We don’t see obvious reason for the need of a slow or delayed degrader. No one has attempted yet to developed a delayed degrader, but this need can certainly change for different target or indications.

Q: If you can’t see in vitro differentiation of a PROTAC from a SM inhibitor at a given target, do you think you can see differentiation from in vivo studies?
A: Yes, there are multiple situations an in vivo differentiation can occur. These include the ability of degrader to overcome the drug resistance, to achieve more potent efficacy and perhaps most importantly selective degradation based on tissue-selective E3 expression.

David Preston
David Preston


David Preston has had 38 years of healthcare experience with publicky Traded and Private companies in the fields of Phammaceuticals, Animal Health and Biotechnology as a Board Member. The last 30 years of his xperience has been in China, Taiwan and Hong Kong building successful igh growth businesses. David Has been Chaiman and CEO for Greater China for Sanofi and Boehringer – Ingelheim as well as the Janssen Corporation since 1991 in China. During this time he build high Growth ousinesses in China through diversified strategies in Innovative Pharmaceuticals. branded Generics. Biotechnology. and Animal Healthcare.

Key highlights in this period indluded building of the first Westem Multinational Biotechnoloqy C.M.O. facility as well as obtaining the first Test CM.OJ MAHI license. Establishment of a number of High tech Vaccine Plants, and R and D facilities in in the field of Animal Health. Signing and development of numerous JV’s as well as Wholly owned Subsidiaries. Mergers and Acquisitions across Phamaceutical’s. Animal Health. and Biotechnology industries

David’s achievement’s in the Healthcare industry and it Growth and development in China is widely recognized By the Chinese Govemnment and the City of Shanghai In 2013 he was awarded the Silver Magnolia ollowed in 2015 the Gold Magnolia award. This was then followed by being awarded in 2017 the Honorary Citizen of Shanghai by 40th People’s Municipal Congress of Shanghai. David Holds a Business Science Degree

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Filippo de Vecchi

Director, Advent Partner

Filippo de Vecchi joined Advent in February 2000. He started in the Advent São Paulo office, then moved to Milan in 2002, in 2012 set up the Advent office in Shanghai and in 2016 set up the Hong Kong office. Before joining Advent, he was a senior consultant with Value Partners, in São Paulo and Milan, focusing on strategy and organization in the automotive, energy, cable and media sectors. He began his career at Wasserstein Perella & Co., working as an analyst in the Mergers and Acquisitions department in London and New York. Filippo holds an undergraduate degree cum laude in Economics, with a major in Business Administration, from the LUISS University and an MBA from Columbia Business School, where he currently serves as a member of the Board of Overseers.

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Andrew Li
Andrew Li

Director, Advent Partner

Andrew Li joined Advent in 2012. He previously worked at Warburg Pincus, HSBC PE, Solera Capital and Credit Suisse where he focused on the retail and consumer, healthcare, industrial, and energy sectors. Andrew has worked in finance and private equity throughout the U.S. and China since 1999. Andrew holds a BA from Middlebury College and an MBA from Harvard Business School.    

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Michael Miltenberger
Michael Miltenberger

Director, Advent Partner

Michael Miltenberger  joined Advent in 2011 as an associate on the healthcare team. Following business school, he rejoined Advent’s Boston office, focusing on healthcare investments. Prior to Advent, Michael was a consultant at McKinsey & Company in their Washington DC office, serving a range of healthcare and private equity clients. Michael earned a BA, cum laude, from Harvard College and an MBA from Harvard Business School, graduating with High Distinction as a Baker Scholar and a Harvey Fellow.

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Masood Tayebi
Masood Tayebi, PhD

Director, Operating Partner

Dr. Masood Tayebi is the Founder of BioDuro. He currently serves as CEO of a nationwide real estate portfolio and is a Partner and Chief Executive Officer of the Bridgewest Group. Prior to BioDuro, Dr. Tayebi was Co-Founder and Chairman of Wireless Facilities, Inc. (NASDAQ: WFI), a global leader in telecommunications outsourcing.

  • Co-Founder of Wireless Facilities, Inc.

  • Co-Founder of BioAtla, LLC

  • Recipient of the Ernst and Young 2000 Entrepreneur of the Year award in San Diego

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Kewen Jin
Kewen Jin, PhD

Director, Operating Partner

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Amit patel
Amit Patel

Director, Operating Partner

Amit Patel has twenty years of healthcare industry experience with publicly-traded, private equity-backed, and start-up companies in the capacity of executive, board member, advisor, and investor.  He is currently Executive Chairman of Azurity Pharmaceuticals (a NovaQuest Capital Management portfolio company) and a board member at BioDuro (Advent International portfolio company), Tergus Pharma (Great Point Partners portfolio company) and Calyptus Pharma.  Recently, Amit was SVP & President of Dosage Form Solutions at Capsugel, a KKR portfolio company (purchased from Pfizer in 2011 and sold to Lonza in 2017).   

Prior to Capsugel, he worked at Dr. Reddy’s Laboratories, Inc. as EVP & Head of North America, and SVP & Head of Global Corporate Development & Strategic Planning. Earlier, Amit was VP of Corporate Development at CTIS, Inc., and Co-founder & CEO of MedOnTime, Inc. (acquired by CTIS).  He started his career as a strategy consultant with Marakon Associates. Amit holds an M.B.A. degree from Harvard Business School, a B.S. degree in Economics from the Wharton School of Business, University of Pennsylvania, and a B.A.S. degree in Systems Engineering from the Moore School of Engineering, University of Pennsylvania.

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Haijun Dong
Haijun Dong

Chief Executive Officer

Dr. Haijun Dong currently serves as global CEO of BioDuro-Sundia. He previously was CEO for over 5 years at PharmaBlock Sciences Inc., a public company listed in the Shenzhen Stock Exchange (300725.SZ). The positions he held prior to PharmaBlock includes, among others, Senior Scientist at Boehringer Ingelheim Pharmaceuticals in Ridgefield, Connecticut; Senior Principal Scientist at Roche in Nutley, New Jersey; Head of DMPK and Drug Safety at Roche China R&D Company in Shanghai; Chief Operating Officer of Eli Lilly China R&D Center in Shanghai.

Dr. Dong received his PhD in organic chemistry from the University of Washington in Seattle, Washington, and MBA from China Europe International Business School in Shanghai. 

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Teo Nee Chuan
Teo Nee Chuan

Chief Financial Officer

Teo Nee Chuan joined us in May 2021 as chief financial officer. Prior to joining us, he was chief financial officer of Huazhu Group from November 2015 to May 2021, and was the chief financial officer for Rnomac International Limited, from November 2011 to August 2015. Mr. Teo worked in DDB Greater China Group, was appointed as the chief financial officer in September 2009, and was additionally appointed as the director of operations in January 2011. He previously served in Focus Media Group and was appointed as the financial deputy director in June 2007. Prior to that, from September 1994 to May 2007, Mr. Teo worked at Ernst & Young and Ernst & Young Business Services Ltd. in various positions in Kuala Lumpur and Toronto, including as a senior manager in the Transaction Advisory Services. Mr. Teo has been an independent director of 111, Inc. (a company listed on the NASDAQ, ticker symbol: YI) since September 2018. Mr. Teo received his Bachelor of Science in Accounting and Financial Analysis degree from The University of Warwick in the United Kingdom in July 1994. He is a Chartered Certified Accountant in the United Kingdom, who has obtained his qualification in July 1998 from The Association of Chartered Certified Accountants, and is a Certified Public Accountant in the United States and Hong Kong, who has obtained his qualification from American Institute of Certified Public Accountants in May 2002 and Hong Kong Society of Accountants in October 2003, respectively.

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TJ Deng, PhD

President, Discovery

Dr TJ Deng joined BioDuro in the initial stages of the company and helped BioDuro grow to an industry leading discovery services organization. He established and managed several scientific departments, including DMPK, before transitioning to a leader of the business and operations functions. Prior to joining BioDuro, Dr. Deng spent six years at PPD, in positions with increasing responsibilities from scientist to scientific manager.




  • Developed the extractable/leachable capabilities at PPD
  • 18 years industry experience

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Kent Payne
Kent M. Payne, PhD

Chief Executive Officer

Kent is distinguished as a business operator and leader in areas of sales, commercial manufacturing and product development. He has extensive executive experience in M&A as well as successfully running, start up, growth and turn around businesses. This includes both Fortune 500 and Private Equity environments. He combines strong business leadership, successful P&L track record, and technical background to strategically lead and grow enterprise value across Biotechnology and Pharmaceutical market segments. He has successfully led the geographic expansion of businesses into Europe, Asia, and South America in addition to the United States.  He currently serves as CEO for BioDuro-Sundia, LLC (an Advent International company). He also currently serves as a board member for Goodwin Biotechnologies (a Signet Healthcare company). 

Prior Roles

  • President, Global CMC Solutions BioDuro-Sundia, a global
  • CEO Socorro Pharmaceuticals, LLC, a generic pharmaceutical
  • President Americas, Qualicaps Inc.(a Mitsubishi Chemical Holdings subsidiary)
  • Principal Consultant and Partner at CoreFactor LLC, providing executive strategic, licensing and operational advisory services to clients.
  • Vice President/General Manager Catalent Pharma Solutions, Inc. (a Blackstone Group company formed in 2007, formerly part of Cardinal Health)
  • Progressive leadership responsibility at: Novartis, Monsanto and G.D. Searle.  

Prior Brand Position

  • Board Advisor Vitruvias Therapeutics
  • Board Member Qualicaps, Inc. (a wholly owned subsidiary of
    Mitsubishi Chemical Holdings)
  • Board member Technophar, Inc. (a wholly owned subsidiary of
    Mitsubishi Chemical Holdings)
  • Board Advisor, Corporate Strategy Office, Life Science Institute
    Inc. (a wholly owned subsidiary of Mitsubishi Chemical Holdings)
  • Non-executive Chair and Board Member PDS Biotechnology·        (PDSB: NASDAQ)

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John Phillips
John Phillips

Vice President, Business Development (US & EU)

Coming soon…



  • Coming soon…

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Roy Xu
Roy Xu

Chief Strategy Officer

Roy has over 25 years of healthcare industry experience.  He started his career as an orthopedic surgeon.  Roy joined Eli Lilly as a sales rep in 1997.  Since then he has had various roles in market research, business intelligence, BU head, strategy, regional general management, business development etc., both at Eli Lilly and Boehringer Ingelheim (BI).  Roy also spent more than two years in Germany where he was BI’s Director of Corporate Business and Enabling Strategy.

Roy obtained a bachelor’s degree in Clinical Medicine at Zhejiang Traditional Chinese Medicine University, and an MBA from Zhejiang University.



  • 25 years of healthcare industry experience including Eli Lily and Boehringer Ingelheim. 
  • Former Director of Corporate Business & Enabling Strategy at oehringer Ingelheim in Germany.

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San Diego

San Diego - BioDuro-Sundia

Our San Diego site is our corporate headquarters. The facility is home to BioDuro-Sundia’s drug product development technologies and has 9 GMP clean rooms. Development and manufacturing operations are conducted for projects up to Phase III clinical trials.

Size: 44,000 sq. ft.
Featured capabilites: Tableting, Coating, Hot Melt Extrusion, Spray Dried Dispersion

11011 Torreyana Rd.
San Diego
CA 92121
United States

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BioDuro Beijing

Operating since 2006, our Beijing site is home to BioDuro-Sundia’s first wet chemistry operations. With 300 regular fume hoods and 18 scale-up chemistry hoods the Beijing facility houses most of BioDuro’s chemistry operations, while also hosting labs for biology and monoclonal antibody discovery.

Size: 100,000 sq. ft. 
Featured capabilities: Radioactivity Lab, Monoclonal Antibody Discovery, Medicinal Chemistry

No. 29 Life Science Park Road
Changping District Beijing,
P.R. China

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BioDuro- Shanghai Facility

Established in 2012, BioDuro-Sundia’s Shanghai facility has been growing with its departments. The cutting edge facility contains labs for ADME, bioanalysis, in vitro assays and translational research. The site includes a 18,000 sq. ft vivarium and 20,000 sq. ft of office space.

Size: 92,000 sq. ft.
Featured capabilities: Scale-up Chemistry, Discovery Biology, DMPK, In Vivo Pharmacology

No. 233 North Fu Te Road
Waigaoqiao Free Trade Zone
Shanghai, 200131
P.R. China

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Cathy Yen
Cathy Yen

Director, Operating Partner

Cathy joined the Board of Directors of BioDuro-Sundia in 2020, with the Advent-led acquisition of Sundia and creation of BioDuro-Sundia. Prior to that, she was Chairman of the Board at Sundia Meditech Group, where she was the key architect of Sundia’s strategic vision and growth. Under her leadership, Sundia solidified its position as one of the leading pre-clinical CROs in China.

Prior to Sundia, Cathy had a distinguished career as a seasoned venture capitalist, having led numerous investments in high-growth companies in Asia. Cathy served as a Partner of AsiaVest Partners, TCW/YFY Ltd., a global venture capital firm, for over a decade, Vice President at Global Financial Services, Vice President at Crimson Ventures/Chinatrust Bank and Senior Manager at Fortune Capital. She brings over 20 years of experience in corporate finance, accounting, strategic planning and private equity investments. 

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Wuxi - BioDuro

Established in 2019, BioDuro-Sundia’s fully integrated discovery facility located at the heart of Jiangsu Wuxi Life Science & Technology Industrial Park with plans of growing staff to 1000+ scientists.

Size: 300,000 sq. ft.
Featured capabilities:
Discovery Chemistry & Biologics, Biology, DMPK, Pharmacology, CMC Services

no.1699,Huishan avenue
Huishan Economic 
Development Zone,Wuxi
P.R. China

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Hebei - Sundia

Established in 2011, this pilot plant this handles mg to kg scale up.

Size: 45,208 sq. ft.

Featured capabilities: SFFS Chemistry: mg to kg scale up
(150 hood)

238 Changjiang Road
Hebei province
P.R. China

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