Project Development
Resume:
Pranab K. Mishra, Ph.D.
San Diego CA 92131
**************@*****.***
Lead Medicinal Chemist with proven track record in the areas of infectious diseases,
vaccine adjuvant, oncology, metabolic diseases, auto-immune disorder, and extensive
expertise in developing small molecule therapeutics, including building IP position,
structure-based drug design, extensive SAR study, pre-clinical and clinical candidate
selection. Effectively drive medicinal chemistry projects from early stage discovery
research through IND enabling studies. Creative, self-motivated with strong work ethic.
Strong reputation in solving tough problems in SAR study and ADMET optimization to
deliver potent, oral drugs.
PROFESSIONAL EXPERIENCE
Genomics Institute of the Novartis Research Foundation, San
Diego, CA
03/2010 – 02/2013
Investigator
Responsibilities:
Lead Medicinal Chemist in the team for Anti-Leishmania /Anti-Malaria Project
Development of hit to lead and lead optimization for Anti-malarial and Anti-
Leishmania project, independently working in parallel on multiple scaffolds to
determine best
Generation of proof of concept compounds for in vivo efficacy testing for four
distinct series that meet key criteria for in vitro potency and oral exposure
Accomplishments:
Introduction of chemical functionalities to dramatically improve oral PK properties
and cellular selectivity for pathogens over mammalian cells. Utilization of difficult
synthetic chemistry for making enantiopure analogs. One of the scaffold was
transitioned to pre-clinical development
Independently progressed for design and synthesis of specific targeted analogs
in one scaffold which showed significant improvement in mouse efficacy over the
current drugs in the market for Leishmaniasis; subsequently this scaffold was
transitioned to full lead optimization and was key person in bringing rest of the
chemistry team up to speed on SAR, SPR, and synthesis model evaluation
Currently this compound is at the final stage of CSP (compound selection
process) declaration
06/2007 – 03/2010
Research Fellow
Responsibilities:
Lead Medicinal Chemist for Toll Like Receptor 7 Agonist project, oncology B-Raf
project, Itpkb inhibitor project and mPGES-1 inhibitor project:
Sometime worked in parallel in two or three projects
Development of hit to lead and lead optimization and invention of proof of
concept compounds or developing new chemistry for all these projects
Rational modification of Quinaxolinone hit through a systematic SAR for the Itpkb
project
Synthesis of long and difficult carboxylate analog during the lead optimization
studies of the mPGES-1 inhibitor project.
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Accomplishments:
TLR-7 project: Invention of one of the preclinical drug candidates for use as a
vaccine adjuvant. Invention of Topical SMIP-7.7, a toll-like receptor 7 agonist,
that protects against genital herpes simplex virus-2 disease in the guinea pig
model of genital herpes
Efficient SAR optimization to dramatically improve the ADME/PK properties and
biochemical/cellular selectivity for compounds during systematic SAR studies or
lead optimization for all the projects sometime in parallel
B-Raf project: Invention of several compounds that showed good mouse efficacy
Itpkb inhibitor project: Used parallel chemistry, found out quickly that Piperidine
ring to be the best tail group for the Quinaxolinone scaffold. Also invented that
morpholine group to be the best replacement for this piperazine tail group to
increase solubility and PK profiles
mPGES-1 project: Devised a route to introduce that carboxylate group in the
pyridyl ring of the lead compound LFD864. Helped to establish & consolidate IP
position, lower cLogP within reasonable activity, decrease protein binding,
improve solubility
Tanabe Research Laboratories, San Diego, CA
Senior Research Scientist 01/2005 - 11/2006
Responsibilities:
Project Leader and lead synthetic chemist driving an anti-Obesity/metabolic
disease program
Accomplishments:
Identified potent selective orally bioavailable ACC2 (acetyl coenzyme A
carboxylase) inhibitor for the treatment of obesity. Identified the lead compound
with potent in vitro ACC2 inhibitory activity (low single digit nM range), good
selectivity, Oxymax profile, inhibition of fatty acid and TG synthesis, reduction of
tissue MCA content and increased FAO, favorable PK/ADME profile (in both rat
and mouse), in vivo efficacy, good toxicology profile and safety pharmacology
profiles with excellent metabolic stability
Coordinated and laid out project plans and synthetic routes for the chemistry
group. Synthesized reference compounds and lead compounds in multi-gram
quantities
Project successfully transferred to the parent company Tanabe-Seiyaku-Japan
(Currently known as Mitshubishi-Pharma) and moved into the clinical
development stage
Tanabe Research Laboratories, San Diego, CA
Research Scientist 12/2003 - 12/2004
Responsibilities:
Lead synthetic chemist for a growth factor receptor antagonist project for the
treatment of rheumatoid arthritis
Accomplishments:
Identified potent selective orally bioavailable Flt-1 receptor antagonists for the
treatment of rheumatoid arthritis.
High throughput synthesis of a focus library provided a quick access to high
quality chemical leads.
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Rational molecular scaffold design guided by SAR studies led to the invention of
the desired efficacious compound in vivo
Project successfully transferred to the parent company-Japan Tanabe-Seiyaku
and moved into the clinical developmental stage
Tanabe Research Laboratories, San Diego, CA
Research Scientist 04/2002 - 12/2003
Responsibilities:
Lead synthetic chemist for the Store Operated Calcium Ion Channel Program
Synthesis of a focus library via rational SAR
Accomplishments:
Identified potent selective orally bioavailable Store Operated Calcium Ion
Channel inhibitor for auto-immune/inflammatory disorders
High throughput synthesis of a focus library provided a quick access to high
quality chemical leads.
Identified a compound via lead optimization that had excellent potency, in-vitro
enzyme inhibitory activity, ex-vivo activity, favorable PK/ADME properties and
safety and toxicology profiles
Education, Professional Development and Training
Ph.D, Organic Chemistry, Montana State University - Bozeman, Montana
M.A. Organic Chemistry, University of Delaware - Newark, Delaware
M.Tech Polymer Science and Tech, University of Calcutta - Kolkata, West
Bengal, India
B.Sc. (Hons) Chemistry, University of Calcutta - Kolkata, West Bengal, India
Postdoctoral Fellow
July 2000-March 2002
R.W.Johnson Pharmaceutical Research Institute, Raritan, New Jersey
Research Advisor: Dr. William V. Murray
Senior Vice-President, Drug Discovery
Development and utilization of an unprecedented intra-molecular Oxo-Diels Alder
reaction leading to the synthesis and discovery of heterocycles with complex
stereochemistry
Synthesis of bioactive molecules using Oxo-Diels Alder and Aza-Diels-Alder
reactions
Post-doctoral Fellow
April 1997-June 2000
Stanford University and SUNY at Stony Brook
Research Advisor: Prof. Dale Drueckhammer and Prof. Chaitan Khosla
Development of a new route to prepare synthons for synthesis of Co-enzyme A
and its analogs, using 12-18 steps of challenging chemistry
Synthesis of Acyl-carrier protein analogs (bioactive molecules) for exploration of
polyketide synthase pathways.
Memberships/Awards/ Honors
American Chemical Society, 1996-present
NIH Fellowship, Stanford University and SUNY at StonyBrook
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Senior Research Fellowship, Indian Institute of Technology, Kharagpur, India
Council of Scientific and Industrial Research M. Tech Fellowship from Government of
India.
Ex-member: Indian Institute of Engineers, Calcutta, India
REFERENCES
1. Arnab K Chatterjee, Ph. D.
Principal Investigator
California Institute for Biomedical Research (Calibr)
11119 N. Torrey Pines Rd. Suite 100
La Jolla, CA 92037 USA
Ph: 858-***-****
Email: ***********@******.***
2. Ila Sircar, Ph.D.
Ex-Director, Chemistry Division
Tanabe Research Laboratories USA Inc.
4540 Towne Centre Ct, San Diego, CA 92121
Ph: 858-***-****
Email: ***.******@*****.***
3. William V. Murray, Ph.D.
Head of Chemistry
Janssen Pharmaceutical Companies of Johnson and Johnson
Cardiovascular and Metabolic Research
1400 Mckean Road
Spring House, PA 19477
Phone: 215-***-****
Email:*******@***.***.***
Pranab Mishra CV Addendum
SELECTED PUBLICATIONS AND PATENTS
1.Topical SMIP-7.7, a toll-like receptor 7 agonist, protects against genital herpes simplex
virus-2 disease in the guinea pig model of genital herpes.
Bernstein DI, Cardin RD, Bravo FJ, Earwood J, Clark JR, Li Y, Mishra P, Li C, Nayak
BP, Miller AT, Wu TY, Cooke MP, Valiante NM. Antivir Chemistry and Chemotherapy.
2012, Dec.
2. Preparation of phenylimidazole derivatives for use as mPGES-1 inhibitors. Chianelli,
Donatella; Molteni, Valentina; Albaugh, Pamela A.; Choi, Ha-Soon; Loren, Jon; Wang,
Zhicheng; Mishra, Pranab. PCT Int. Appl. (2010), WO 201******* A2 20101104.
3. Preparation of benzonaphthyridines as TLR activity modulators. Wu, Tom Yao-
Hsiang; Li, Yongkai; Cortez, Alex; Zou, Yefen; Mishra, Pranab; Zhang, Xiaoyue;
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Skibinski, David; Singh, Manmohan; Valiante, Nicholas. From PCT Int. Appl. (2009),
WO 200-***-**** A1 20090911.
4. An intramolecular oxo-Diels-Alder approach to 1-oxo-1,2,3,3a,4,7a-hexahydro-
pyrano[3,4-c]pyrrole-4-carboxylic acid ethyl esters. William V. Murray*, Pranab. K.
Mishra, Ignatious J. Turchi, Dorota Sawicka, Amy Maden, Sengen Sun.; Tetrahedron,
2003, 59, (45), 8955-8961.
5. Synthesis of densely functionalized pyrrolidinone templates by an intramolecular oxo-
Diels-Alder reaction. William V. Murray*, Pranab K. Mishra, Sengen Sun, and Amy
Maden.; Tetrahedron Letters, 2002, 43, (41), 7389-7392.
6. Synthesis of a novel cyclic pentacovalent phosphoenol ether derived from a dienone.
Approaches to the syntheses of phosponate analogs of sphingomyelin, sphingosine-1-
phosphate and ceramide-1-phosphate. Cynthia K. McClure* and Pranab K. Mishra.
Tetrahedron Letters, 2002, 43, (30), 5249-5253.
7. Preparation of densely functionalized pyrrolidine libraries in situ and resin bound via
an intramolecular Diels-Alder (IMDA) reaction. William V. Murray*, Pranab. K. Mishra, &
Sengen Sun. PCT Int Appl (2002), WO 200-***-**** A1 20020919.
8. Identification of yacE (coaE) as the structural gene for dephosphocoenzyme A kinase
in Escherichia coli K-12. Pranab K. Mishra, Peter K. Park and Dale G.
Drueckhammer*. Journal of Bacteriology, 2001, 183 (9), 2774-2778.
9. Investigating the role of the geminal dimethyl groups in Coenzyme A: synthesis and
studies of a di-demethyl analog. K. W. Vogel, Lucy M. Stark, Pranab K. Mishra, W.
Yang and Dale G. Drueckhammer*, Bioorganic and Medicinal Chemistry, 2000, 8, 2451.
10. Coenzyme A analogs and derivatives: synthesis and applications as mechanistic
probes of Coenzyme A ester-utilizing enzymes. Pranab K. Mishra and Dale G.
Drueckhammer*, Chemical Reviews, 2000, 100 (9), 2383-3309.
11. Novel cofactor derivatives and cofactor-based models, Pranab K. Mishra and Dale
G. Drueckhammer*, Current Opinion in Chemical Biology, 1998, 2, 758.
12. Synthetic studies toward the preparation of phosphonate analogs of sphingomyelin
and ceramide 1-phosphate using pentacovalent organophospholene methodology",
Cynthia K. McClure*, P. K. Mishra, and C. W. Grote, J. Org. Chem. 1997, 63, 2437.
13. Synthetic studies toward the preparation of phosphonate analogs of sphingomyelins
and ceramide 1-phosphate using pentacovalent organophosphorus methodology.
Cynthia K. McClure*, Pranab Mishra; Phos., Sulf. and Silicon, 1996, 111, 709.
Some more patents and papers pending on Malaria and Leishmania
SELECTED ABSTRACTS
1.Synthesis of densely functionalized pyrrolidinone templates by IMDA directed remote
hydroxylation. Pranab K. Mishra, Sengen Sun, and William V. Murray; Abstract of
papers, 222nd ACS National Meeting, Chicago, IL, USA, August 26-30, 2001.
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2.Recent advances in Coenzyme A analog synthesis. Pranab K. Mishra, Dale G.
Drueckhammer, Abstract of papers, 220th ACS National Meeting, Washington DC, USA,
August 20-24, 2000.
BOOK CHAPTERS
C. K. McClure*, P. K. Mishra, "Bis(4,5-dimethyl-2-oxo-1,3,2-dioxaphospholenyl) oxide".
Encyclopedia of Reagents for Organic Synthesis, John Wiley & Sons, Ltd., 1995, 1, p
503-504.
Keinan, E., C. K. McClure*, P. K. Mishra, "Diiodosilane", Encyclopedia of Reagents for
Organic Synthesis, John Wiley & Sons, Ltd., 1995, 3, p1905-1907.
PRESENTATIONS AND POSTERS
March 25-29, 2012, Division of Medicinal Chemistry, 243rd National Meeting and
Exposition, San Diego, CA, Arnab Chatterjee, Advait Nagle, Tao Wu, Tomoyo Sakata,
Robert Moreau, Jason Roland, Pranab Mishra, David Tully, Valentina Molteni etal. Cell-
based optimization of novel anti-parasitics.
March 15-16, 2011
AntiMalaria Meeting,
Royal College of Surgeons, London UK, Arnab Chatterjee, Advait Nagle, Tao Wu,
Tomoyo Sakata, Robert Moreau, Jason Roland, Pranab Mishra, David Tully, Valentina
Molteni etal. “Discovery of novel anti-malarials through cell based medicinal chemistry
optimization of HTS hits.”
June 23, Portland, Oregon, 1999
ACS Northwest Regional Meeting, (NORM ’99),C. K. McClure*,P. K. Mishra, "Synthetic
Studies toward the preparation of Phosphonate Analogs of Sphingomyelin and
Ceramide 1- Phosphate using Pentacovalent Organophosphorus Methodology."(Oral
presentation)
October 23, Gainesville, Florida, 1996
7th Symposium on the latest trends in Organic Synthesis, C. K. McClure, P.K. Mishra,
B.-Z. Cai, R. J. Fisher, J. S. Link, “Recent advances in the use of pentacovalent
organophosphoranes in organic synthesis”, invited talk.
7-11 July, New Hampton, NH, 1996
Gordon Research Conference on heterocyclic compounds, C. K. McClure, P. K. Mishra
(Invited talk) “Synthetic Studies Toward the preparation of Phophonate Analogs of
Sphingomyelin and Ceramide 1-Phosphate using Pentacovalent Organophosphorus
Methodology,” invited talk.
April 2, Anaheim, California, 1995
209th ACS National Meeting, C. K. McClure, P. K. Mishra, “Synthetic Studies Toward
the preparation of a Phophonate Analog of Sphingomyelin using Pentacovalent
Organophosphorus Methodology." invited Paper
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July 10, New Hampton, NH, 1994
Gordon Research Conference on Heterocyclic Compounds, C. K. McClure*, K.-Y. Jung,
and C. W. Grote, K. B. Hansen, M. P. Sant, P. K. Mishra, K. L. Mayhew, M. W. Embrey,
B. A. O'Neil, "Novel Synthetic Routes to Heterocycles via Pentacovalent Phosphorus
and Photochemical Methodologies." invited Paper.
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