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PROTACs

(PROteolysis TArgeting Chimeras)

PROTACs are a specific type of molecule or compound designed for targeted protein degradation (TPD). TPD involves employing heterobifunctional small molecules known as “Degraders,” like PROTAC Degraders, or utilising PROTAC services to effectively reduce the levels of specific target proteins within cells. PROTACs are heterobifunctional small molecules consisting of a target binding handle bridged via a chemical linker to an E3 ligase handle which hijacks the endogenous ubiquitin machinery to target proteins, resulting in subsequent ubiquitination and degradation of your target of interest.

PROTAC services and process

PROTACs provide significant therapeutic potential with possible prolonged pharmacodynamics, improved potency, and ability to target proteins previously thought of as “undruggable”.

o2h discovery offeres intigrated PROTAC synthesis services as well as a bespoke and customisable “off-the-shelf” PROTAC toolbox to jump-start your targeted protein degradation program, along with our strong expertise in medicinal and synthetic chemistry.

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o2h discovery’s expertise in PROTAC services and targeted protein degradation:

In the last few years, we have developed strong expertise in PROTAC services, synthesis and screening of complex PROTAC molecules, and related specialty chemistry. We provide comprehensive solutions for the design and synthesis of PROTAC building blocks, linkers, compound libraries, and related intermediates to help proof and de-risk your targeted protein degradation approach.Read More

We also developed a range of biology capability along with analytical methods and purification protocols for the isolation of high-quality complex PROTAC molecules and their accurate characterisation. Several building blocks have been prepared at gm scale with reliable synthetic routes and purification methodologies.

o2h discovery can provide you a range of E3 ligase ligands from our o2h PROTAC toolboxTM for the quick synthesis of PROTAC equipped with a variety of linkers for rapid assembly of degrader analogues to accelerate your drug discovery and development process with our PROTAC services.Read Less

Listen to what our client says about our protac services

- Julian Blagg, Executive VP, Drug Discovery
- Martin Drysdale, Chief Scientific Officer

o2h PROTAC toolbox™

we offer PROTAC services with our customizable PROTAC toolbox™ kit of over 100 monomers, including various linkers, ligands and necessary controls. They can provide significant therapeutic potential with possible prolonged pharmacodynamics, improved potency, and ability to target proteins previously thought of as “undruggable”.

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protein degradation - biology

biology evaluation suite to estimate ternary complex formation and targeted protein degradation

o2h biologists can support you in addressing the following questions:

Q.Is my target degraded?

Q.Is my target ubiquitinated?

Q.Do they form a ternary complex?

Q.Are they soluble and cell permeable?

Q.What is the binary affinity for POI and E3 ligase?

Q.What is the phenotypic consequence of target degradation?

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case study

PROTAC induced ternary complex formation and kinetics of targeted protein degradation

PROTAC-induced BRD4-VHL ternary complex formation and BRD4 protein degradation. HEK292 cells transfected with NanoLuc-BRD4 donor plasmid and Halo-Tag-VHL acceptor plasmid at 1:100 ratio. Subsequently cells treated with 1uM MZ1 or AT1 PROTAC and compared with untreated DMSO control.

(A, B) Indicates ternary complex formation at 6h (C,D) BRD4-BD2 protein levels at 6h (E,F) real-time ternary complex formation with BRD4-B2/VHL following PROTAC treatment (G,H) real-time kinetics of BRD4-BD2 protein degradation following PROTAC treatment. MG132, a potent, reversible and cell permeable proteasomal inhibitor rescues BRD4 degradation in all condition.

PROTACs purification - analytical capabilities

o2h discovery has analytical capabilities in purification of PROTACs molecules for targeted protein degradation and PROTAC services

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Purification of multiple PROTAC compounds containing various Linkers/Ligands like VHL or CRBN.
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5 years of hands-on experience on PROTAC compounds purification, Available different column chemistry for the purification of PROTAC molecules.
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Successfully enriched the purity level from ~20% to >95%
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Well experienced Analytical team to handle purification from mg to g scale.
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Attained up to 60% practical recovery from prep purification.
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Have effectively purified no. of PROTAC compounds via Prep. HPLC at various scales (mg/g).

case study - VHL ligand chemistry

  • Purified the mentioned PROTAC-molecule by reversed phase Prep. HPLC using basic modifier(pH~9) in water and acetonitrile with gradient elution and the column chemistry used was C18.
  • Collected pure fractions were concentrated using lyophiliser.
  • Crude Quantity was ~1.1 gm with 30% purity of desired product.
  • Successfully isolated ~100 mg in pure form (with 30% recovery)
  • After purification - 95% purity achieved.
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our team

prashant shah

Prashant Shah

CEO - o2h discovery and Co-Founder - o2h group

Prashant's Biography

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Prashant Shah

CEO - o2h discovery and Co-Founder - o2h group

Prashant is a serial entrepreneur in life sciences and tech in which one of those companies was acquired by a public company. He is currently active in seed investing (a portfolio of ~50 companies), product/IP development, services, and building lab/office infrastructure. The early career was with the Strategy group at Accenture. He has a BEng, an MSc, in which he worked on the Human Genome Program at the Sanger Centre, and an MPhil in Management from the Judge Institute. Prashant is also a General Partner in the o2h SEIS/EIS Human Health Funds.


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Sunil

Sunil Shah

CEO - o2h Ventures and Co-Founder - o2h group

Sunil's Biography

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Sunil Shah

CEO - o2h Ventures and Co-Founder - o2h group

A serial entrepreneur having begun a career in the Life Sciences team at PA Consulting group followed by co-founding two companies in the information technology and life sciences sector. The second of these companies, Oxygen Healthcare Ltd was acquired by Piramal Enterprises Ltd (BSE: PEL). Sunil co-founded o2h ventures which involves discovery services / collaborations, seeding drug discovery, academic in-licensing and biotechnology incubation. Sunil has a degree in Biochemistry and an MBA from Cambridge University


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Andy Morley

Andy Morley

Chief Scientific Officer

Andy's Biography

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Andy Morley

Chief Scientific Officer

Andy is a highly experienced and accomplished Medicinal Chemist with over 25 years of experience in major pharmaceutical companies such as Sanofi-Aventis and AstraZeneca. He has extensive experience across all phases of drug discovery and has played a key role in the development of five candidates that have reached clinical trials. Andy is a prolific author and inventor, with over 55 publications and patents to his name. Since 2013, he has been working full-time with o2h Limited, where he leads the scientific evaluation of investment opportunities and provides scientific support. He has also served as CSO for two early-stage collaborations within the o2h Ventures portfolio, demonstrating his ability to successfully guide drug discovery projects from concept to clinical development.


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David Davies - o2h

David Davies

Head of Medicinal Chemistry

David's Biography

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David Davies

Head of Medicinal Chemistry

David Davies has 25 years of experience in medicinal chemistry within the pharmaceutical industry with a focus on the antibacterial area (clavulanates, penicillinates, pseudomonates and bacterial topoisomerase inhibitors). He previously worked at GSK and currently holds a part-time academic position at University College London (UCL). He served as the Head of Medicinal Chemistry at Antabio for nearly a decade, specialising in antibacterial research, and has extensive experience managing chemistry projects in multiple countries including France, UK, India and China. He is the inventor of 40 patents and has authored 37 publications.


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