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Wednesday 4 May 2016

Sharan Bagal

.

Sharan Bagal CChem MRSC

Medicinal Chemistry Team leader - Worldwide Medicinal Chemistry, Senior Principal Scientist at Pfizer Neusentis
LINKS
https://uk.linkedin.com/in/sharan-bagal-cchem-mrsc-81729919
https://www.facebook.com/sharan.bagal

Summary

Summary: 10 years pharmaceutical industry experience, hardworking, highly motivated individual with demonstrable impact and candidate delivery
Key highlights
- Direct inventorship role in the identification of 5 clinical candidates, 3 of which are in Phase I/II
- 33 publications including 13 published patents
- 2012 European Federation for Medicinal Chemistry Prize winner “Young Medicinal Chemist in Industry”
- Granted 7 department impact awards and numerous additional awards for effective problem solving
- Project Managed cross-functional teams within a project to ensure timely delivery of key milestones
- Excellent team member used to working in a multi-disciplinary environment
- Strong organisational and negotiation skills both in an internal and external environment
- Experience with ligand- and structure-based drug design
- Excellent scientific writing skills, oral communication skills, and data visualisation and analysis ability
- Direct line management of up to 4 chemistry graduates per year and 1 Ph.D student
- Internationally recognised subject matter expert through organisation of collaborations with academics, working on RSC, GRC and EFMC committees, referee work, internalisation of external technology, and tutoring at Oxford
- Ability to identify and apply novel methodology to current drug discovery problems through successfully securing departmental funding based on written proposals of work that are accepted by the leadership team
Specialities: medicinal chemist, clinical candidate, research associate, drug discovery, chemist, research, scientist, project manager, preclinical protocol and dossier writing, regulatory affairs, CMC, Good Clinical Practice, GCP

Experience

Senior Principal Scientist Medicinal Chemistry Team Leader

Pfizer Neusentis
– Present (5 years 1 month)Cambridge, United Kingdom
I am 1 of 8 medicinal chemists chosen from Pfizer Sandwich Chemistry (~150 chemists) to set up the Pain Chemistry unit in Cambridge UK after Pfizer Sandwich chemistry closure. I worked on 5 different projects (ion channel, kinase) that were ligand- and structure-based, in the exploratory and candidate seeking arena being accountable for timely project delivery. This role involved organisation and management of cross-functional teams together with leading the chemistry strategy. I regularly presented to the leadership team in order to secure funding for research activities to enable project progression. Our team delivered 2 clinical candidates and numerous hit-to-lead series to underwrite 2 Lead Development transitions. On several occasions I managed cross site drug discovery project teams – US/UK, India/UK, Europe/UK.
(Open)1 honor or award

Principal Scientist Medicinal Chemistry Team Leader

Pfizer
(5 years)Pfizer Sandwich, Kent, UK
I worked on 3 different projects (ion channel, kinase, GPCR) that were ligand- and structure-based, in the exploratory and candidate seeking arena, across 2 therapeutic areas (Pain and Allergy/Respiratory). Moreover our team designed, synthesised and advanced 3 compounds for clinical development that are currently in Phase I/II.

Postdoctoral Research in Synthetic Chemistry

Professor Samir Z. Zard
(1 year)Ecole Polytechnique, France
In collaboration with Professor S. Z. Zard, I have developed a novel acyl radical equivalent. Furthermore, I have devised a facile method for the generation of radicals from aldehydes.
(Open)1 honor or award

Graduate Research Assistant

National Physical Laboratory
(5 months)Teddington, UK
In collaboration with Dr. B. Nimmo, research was conducted into the calibration of a scanning vibrating electrochemical probe. I designed novel experiments followed by publication of a detailed report.

Honors & Awards

EFMC Prize for Young Medicinal Chemist in Industry

European Federation for Medicinal Chemistry (EFMC)

EFMC Prize for Young Medicinal Chemist in Industry
“The EFMC Prize for Young Medicinal Chemist in Industry” was initiated to acknowledge and recognize an outstanding young medicinal chemist (≤ 35 years old) working in industry within Europe. The Prize is given annually and consists of a diploma, € 1.000 and an invitation for a short presentation at an EFMC symposium. .

Egide scholarship to fund postdoctoral studies

Egide

Syngenta Postgraduate Scholarship in Organic Chemistry

Syngenta

Scholarship to fund postgraduate studies.

University Graduate Studentship Scheme (UGGS)

Glaxo Wellcome Prize

Glaxo Wellcome

Glaxo Wellcome Prize is presented based upon experimental work and written submission

Oxford University Scholarship for academic excellence

Oxford University

Oxford University Scholarship for academic excellence is awarded when a 1st year student passes Prelim examinations with Distinction honours, and thus becomes a Scholar

Patents

Preparation of N-acylpiperidine ethers as kinase inhibitors

United States WO2015092610
Filed 2015

Tropomyosin-related kinase inhibitors

United States WO2015170218
Filed 2015

Tropomyosin-related kinase inhibitors

United States WO2015159175
Issued 2015

Kinase Inhibitors

United States WO 2014053968
Issued 2014

Kinase Inhibitors

United States WO 2014053967
Filed 2014

Kinase Inhibitors

United States WO 2014053965
Filed

Chemical Compounds

United States WO 2013061205
Issued 2013

Benzimidazole Derivatives

United States WO 2013114250
Issued 2013

Bagal, S. K.; Skerratt, S. et al. “Kinase Inhibitors” PCT Int. Appl. 2012

United States WO 2012137089
Filed 2012

Cyclobutenedione Derivatives

United States WO 2010131147
Filed 2010
2 inventors:

Cyclobutenedione Derivatives

United States WO 2010131146
Filed 2010

Cyclobutenedione Derivatives

United States WO 2010131145
Issued 2010

Pyridine Derivatives

United States WO 2008135826
Issued 2008

Publications

Concise and highly selective asymmetric synthesis of acosamine from sorbic acid

Bagal, S. K.; Davies, S.; Scott, P. M. “Concise and Highly Selective Asymmetric Synthesis of Acosamine from Sorbic Acid”, Tetrahedron Letters, 2010, 52, 2216

Syntheses of the Enantiomers of 1-Deoxynojirimycin and 1-Deoxyaltronojirimycin via Chemo- and Diastereoselective Olefinic Oxidation of Unsaturated Amines

Bagal, S. K.; Davies, S.; Scott, P. M. “Syntheses of the Enantiomers of 1-Deoxynojirimycin and 1-Deoxyaltronojirimycin via Chemo- and Diastereoselective Olefinic Oxidation of Unsaturated Amines”, Journal of Organic Chemistry, 2010, 75, 8133

An Efficient Oxidation & Ring-Contraction Approach to Synthesis of Racemic 1-Deoxynojirimycin & 1-Deoxyaltronojirimycin

Bagal, S. K.; Davies, S.; Scott, P. M. “An Efficient Oxidation and Ring-Contraction Approach to Synthesis of Racemic 1-Deoxynojirimycin and 1-Deoxyaltronojirimycin”, Organic Letters, 2009, 12, 136

Recent advances in biomimetic natural product synthesis

Bulger, P. G.; Bagal, S. K.; Marquez R. “Recent Advances in Biomimetic Natural Product Synthesis”, Natural Products Reports, 2008, 25, 254

Radicals from Aldehydes. A Convergent Access to Dienes and d-Lactones

Bagal, S. K.; Tournier, L.; Zard, S. Z. “Radicals from Aldehydes. A Convergent Access to Dienes and d-Lactones”, Synlett, 2006, 10, 1485

Cyano(ethoxycarbonothioylthio)methyl benzoate: A Novel One-Carbon Radical Equivalent

Bagal, S. K.; de Greef, M.; Zard, S. Z. “Cyano(ethoxycarbonothioylthio)methyl benzoate: A Novel One-Carbon Radical Equivalent”, Organic Letters, 2006, 8, 147

Regioselectivity of Dimerisation of Butenolides via Captodative Stabilised Radicaloid Intermediates

Bagal, S. K.; Adlington R. M.; Brown, R. A. B.; Baldwin, J. E. Tetrahedron Letters, 2005, 46, 4633

Dimerization of Butenolide Structures. A Biomimetic Approach to the Dimeric Sesquiterpene Lactones (±)-Biatractylolide and (±)-Biepiasterolide

Bagal, S. K.; Baldwin, J. E.; Adlington R. M.; Marquez R. Journal of Organic Chemistry, 2004, 69, 9100

Biomimetic Synthesis of Biatractylolide and Biepiasterolide

Bagal, S. K.; Baldwin, J. E.; Adlington R. M.; Marquez R. Organic Letters, 2003, 5, 3049

Studies towards the Biomimetic Synthesis of Bisesquiterpenoid Lactones

Bagal, S. K.; Baldwin, J. E.; Adlington R. M.; Marquez, R. Tetrahedron Letters, 2003, 44, 4993

Full efficacy with no CNS side-effects: unachievable panacea or reality? - DMPK considerations in design of drugs with limited brain penetration

Bagal, S. K.; Cole, S. et al. “Full efficacy with no CNS side-effects: unachievable panacea or reality? - DMPK considerations in design of drugs with limited brain penetration” Xenobiotica, 2011, 1
1. Optimising drug properties can be an important strategy to limit penetration into the CNS and offers advantages
in reducing the risk of undesirable neurological effects
2. When considering the design of these drugs it is important to consider the relative influx and efflux rates at the
relevant biological membranes
3. The highest degree of restriction at the brain is probably achievable by...more

Successful medicinal chemistry strategies in the TLR7 agonist programme to avoid aldehyde oxidase metabolism

Bagal, S. K.; Pryde, D. et al. “Successful medicinal chemistry strategies in the TLR7 agonist programme to avoid aldehyde oxidase metabolism” Bioorganic and Medicinal Chemistry Letters, 2012, 2856

Voltage Gated Sodium channels as Drug Discovery Targets

Bagal, S. K.; Pryde, D. et al. “Successful medicinal chemistry strategies in the TLR7 agonist programme to avoid aldehyde oxidase metabolism” Bioorganic and Medicinal Chemistry Letters, 2012, 2856

Discovery and optimization of selective Nav1.8 modulator series that demonstrate efficacy in preclinical models of pain

Bagal S. K. et al. “ Discovery and optimization of selective Nav1.8 modulator series that demonstrate efficacy in preclinical models of pain”, ACS Medicinal Chemistry Letters 2015, 650

Recent progress in sodium channel modulators for pain

Bagal S. K. et al. “Recent progress in sodium channel modulators for pain”, Bioorganic & Medicinal Chemistry Letters 2014, 3690

Designing peripheral drugs for minimal brain exposure, book chapter

Bagal S. K. et al. “Designing peripheral drugs for minimal brain exposure”, book chapter in Blood-Brain Barrier in Drug Discovery: Optimizing Brain Exposure of CNS Drugs and Minimizing Brain Side Effects”, Wiley, 2014, Chapter 20, 446

PF-1247324, a structurally novel selective Nav1.8 blocker that reduces excitability in human sensory neurons in vitro and attenuates nociception in models of inflammatory and neuropathic pain

Bagal, S. K.; Payne, L. et al. British Journal of Pharmacology, 2015, 2654

Restricting CNS penetration of drugs to minimize adverse events: role of drug transporters

Bagal S. K. ; Bungay, P. ; “Restricting CNS penetration of drugs to minimize adverse events: role of drug transporters”, Drug Discovery Today Technology, 2014, 79

Ion Channels as Therapeutic Targets: A Drug Discovery Perspective

Bagal, S. K.; Pyrde, D. et al. “Ion Channels as Therapeutic Targets: A Drug Discovery Perspective”, Journal of Medicinal Chemistry. 2013, 593

Minimising drug exposure in the CNS whilst maintaining good oral absorption

Bagal S. K. ; Bungay, P. “Minimising drug exposure in the CNS whilst maintaining good oral absorption”, ACS Medicinal Chemistry Letters, 2012, 948

Education

University of Oxford

PhD, Organic synthesis

(Open)2 honors and awards

University of Oxford

MChem ( Masters + B.Sc), Chemistry

First Class Honours (within top 10 of year / Top 3%)
(Open)2 honors and awards

Cornerstones of Management, Pfizer

People Management, Pass

Highly interactive and intensive program developed to build managerial capability and capacity across the global organization. It is comprised of three face-to-face workshop experiences geared to develop key manager accountabilities that align with your role as a manager:
 Delivering Results - Expectations of a Pfizer Manager
 Engaging Talent - Leading People, Teams and Projects Successfully
 Shaping the Future - Coaching & Developing for Peak Performance

Organizations

EFMC-ISMC 2016:

Local organising committee member for 2016 EFMC conference
Starting

RSC Biorganic and Medicinal Chemistry Section

RSC Bio-Org and Med Chem Section Committee Member: Organise RSC conferences/UK education
Starting
Transporters conference organiser 2014
Anglo Nordic Medicinal Chemistry Conference Chair organiser

Gordon Research Conference

Part of organising committee and Session chair
Starting

American Chemical Society

Member
Starting

Royal Society of Chemistry

MRSC and RSC BMCS comittee member
Starting




Dr. Sharan K. Bagal (1978) graduated with first class honours in MChem in 2001 from the University of Oxford, U.K. where she subsequently completed her DPhil in chemistry in 2004 under the supervision of Professor Sir Jack Baldwin and Dr. Robert Adlington. Her doctorate was based on biomimetic natural product synthesis, in particular, the first total synthesis of two natural products biatractylolide and biepiasterolide via a biomimetic radical dimerisation. Sharan then moved to Professor Samir Zard’s group at the École Polytechnique in France as a postdoctoral researcher studying xanthate-based radical chemistry. This work led to the development of a novel acyl radical equivalent, along with a facile method for the generation of radicals from aldehydes.
In 2006 Sharan joined Pfizer Global Research and Development, Sandwich, UK as a medicinal chemist (www.pfizer.com), and is now a Senior Principal Medicinal Chemist at Pfizer Neusentis in Cambridge, UK (www.neusentis.com) with a focus on drug discovery targets for the treatment of pain. Sharan’s research interests encompass all aspects of medicinal chemistry and she has worked on several drug discovery targets including voltage-gated ion channels, GPCRs and protein kinases e.g. NaV1.8 and CXCR1/2. This work has used ligand-based medicinal chemistry design methods to identify potent and selective ion channel modulators within highly challenging medicinal chemistry space, and highly potent chemokine receptor antagonists with a balanced subtype selectivity profile. More recently, Sharan has used structure-based design methodology to successfully design highly potent receptor tyrosine kinase inhibitors with excellent selectivity and a favourable tissue distribution profile.  Her focus has ranged from hit identification, hit to lead optimisation and candidate selection and Sharan has been directly involved in the invention of two compounds currently undergoing clinical trials.
So far over her career, Sharan has co-authored more than 20 papers and patents. She has a particular interest in aldehyde oxidase (AO) catalysed metabolism, in particular the structural aspects that underpin substrate recognition by AO and the role played by both steric and electronic effects of susceptible ring systems. She has developed several datasets that inform how structural features relate to species-specific metabolism by AO, and hypotheses of how this metabolism can be switched off by design. Sharan has also developed an interest in the design of compounds that penetrate, or are restricted from, the central nervous system (CNS) based on an understanding of CNS-located transporters and compound physicochemistry and the implications of CNS distribution on drug safety. She has delivered several reviews and presentations in this area.

The insider: Mixing synthesis and drug discovery

http://www.rsc.org/chemistryworld/Issues/2009/January/MixingSynthesisAndDrugDiscovery.asp
Sarah Houlton talks to Sharan Bagal about life as a medicinal chemist
Sharan Bagal
Sharan Bagal, Pfizer
If you're considering a career in medicinal chemistry, then talking to Sharan Bagal at pharma giant Pfizer might be just the boost you need. Bagal decided she wanted to be a medicinal chemist during her PhD with Jack Baldwin at Oxford. 'I was keen to find a career that challenged me scientifically and which used my training in organic synthesis,' she says. And after gaining a further year's experience as a postdoc with Samir Zard in France, she accepted a job as a trainee medicinal chemist at Pfizer. She's now been based in their labs in Sandwich, Kent for two-and-a-half years.
'My job is a great mix of synthesis and drug discovery,' she says. 'As a trainee designer, you start off doing a lot of synthesis while your knowledge of medicinal chemistry grows. Learning the subject is fascinating - there are so many new concepts to grasp. While the fundamentals can be learnt from a text book, you can only really learn how to be a medicinal chemist by actually doing the job, getting a 'feel' for designing compounds that have the biological activity we want, and which don't have other biological activities that can cause side-effects. You can only learn this sort of thing from working with and hearing about real-life examples.'
Bagal also loves the fact that she works as part of a team - it's very different from a PhD or postdoc project. 'We're all working on the same project, so there's always other people to talk things through with,' she says. 'The team consists of both medicinal chemists and synthetic chemists. And I don't just work with other chemists - I get to interact with scientists from other disciplines, such as biologists who find out whether the compounds I've designed really are active, and drug metabolism experts who work out whether they are likely to be stable in the body. I've learnt so much just by seeing the results of their experiments and how they match up to our predictions.'
A typical day for Bagal starts with checking whether any new data on the compounds the team has made has arrived. These results determine what next steps will be made in the drug design process - either because the activity they were hoping for is there, or because it isn't. She also checks the literature - alerts arrive in her inbox every night - to help keep on top of the field. And then it's down to the business of designing the next potential lead compound - and getting on with synthesising it.
Stick with the team
'I think it's important to carry on with synthesis while you're training as a medicinal chemist,' she says. 'Otherwise, there's a danger of removing yourself from the rest of the team who work in synthesis while you're learning - and it's important that we all work together. As you gain more experience, the amount of medicinal chemistry you do increases, while the synthesis side decreases. My boss, the team's design lead, is an experienced medicinal chemist who concentrates solely on medicinal chemistry, and there's another trainee medicinal chemist in the team who started a year after I did so is still doing more synthesis than I do.'
Mixing synthesis and drug discovery
While the job market in the pharmaceutical industry is uncertain at the moment and (as with so many other sectors) no one can rely on having a career within a single company for life, Bagal has no regrets about her choice as it offers her great opportunities for learning and promotion.  Bagal supervises a graduate chemist in her team, and mentors a chemist from another team. 'With my supervisee, the focus is very much on practical and technical chemistry skills, whereas it's more going through research papers and problem solving with the graduate I mentor,' she says. 'It's also really useful for me as it makes sure I keep up with what's going on in the literature!'
And she believes there will always be opportunities for good scientists. 'The great thing about medicinal chemistry is that you're faced with problems and you've got a variety of tools to help you solve them,' she says. 'You develop a hypothesis, and synthetic chemistry helps you prove or disprove it. I have so much freedom to try out my ideas and see if they work - and it's very rewarding when they do.
I am learning a whole new science.'









Map of Neusentis
Neusentis 
Research Institute
Address: The Portway Building, Granta Park, Great Abington, Cambridge CB21 6GS, United Kingdom





 


 Ruth McKernan, chief scientific officer for Neusentis Ltd., a unit of Pfizer Inc., speaks during an interview at the company's research centre in Cambridge, ...
 



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