Chemist

SRINIVASA RAO CHERUKU, Ph.D.

** ****** ******, *********, ** 02420

781-***-**** (H); 781-***-**** (M)

********@*******.***

Work authorization: U.S. citizen

PROFILE

Innovative and motivated medicinal chemist with hands-on synthetic and process chemistry skills and proven experience in discovery and development of small molecule-based NCEs for pharmaceuticals and agro products

HIGHLIGHTS

 Worked on diverse chemical classes (heterocycles, peptide-based conjugates, natural product Taxol®)

 Hands-on skills in synthesis, purification, instrumentation techniques, data integration and QA analysis

 Performed non-GLP multi-gram scale-up process and prepared tech-transfers for APIs (2 drug candidates)

 Developed multi-gram scale-up process for creatine ester salts and provided tech-transfer packages

 Semi-synthesized large quantities of Taxol® from its natural precursor, baccatin III via reported route

 Prepared Merck’s nausea drug, Emend® (aprepitant) as a reference compound using chiral procedure

 Designed and synthesized radio-labeled and fluorescent-tagged compounds as molecular probes

 Experienced in advancing hits to preclinical candidates (depression, obesity and Alzheimer’s disease)

Proficient in literature and prior-art searches and acted as IP liaison in filing patent applications

 Demonstrated success playing multi-tasking roles with speed and flexibility in a biotech environment

 Co-authored several research disclosures including patents, publications, and posters/presentations

KNOWLEDGE, SKILLS AND ABILITIES

 New synthetic method development, multi-step and parallel synthesis, exploratory and process chemistry

 Bioconjugation techniques for hapten-peptide constructs and fluorescent tagging; radio labeling

 Hit-lead optimization, SAR analysis, drug profiling by integrated preclinical data interpretation (ADME)

 Hands-on technical skills in compound purification/separation and analytical tools (NMR, LCMS, HPLC)

 Use of scientific databases (SciFinder, MDL, Integrity, IDDB, Tripos, Abase, Lithium) and e-Notebook

 Synthetic route selections for building blocks and targets, and prior-art searches for patentability issues

 Managing chemists (RAs, PhDs) by providing mentorship, scientific direction and information resources

 Worked with outsourcing vendors on synthesis of building blocks, scaffolds and APIs (GMP partners)

 Initiative, detail-oriented, and flexible team player with an aptitude to acquire new knowledge and skills

 Worked effectively with cross-functional discovery teams in a fast-paced, highly matrix environment

PROFESSIONAL WORK EXPERIENCE

Medicinal Chemist (contract-term), GlaxoSmithKline, Waltham, MA 12/08 – 03/09

 Design, synthesis and SAR of new small molecule-based hits from Encoded Library Technology (ELT)

Senior Principal Scientist, Epix Pharmaceuticals, Lexington, MA 10/02 - 10/08

(Formerly called Predix Pharmaceuticals)

 Worked on discovery of CNS-targeted drug agents acting on G-Protein Coupled Receptors (GPCRs)

 Held significant role as key inventor and scientific expert in new drug design and hit-to-lead optimization

 Devised multi-step synthetic routes for challenging targets and provided chemistry solutions

 Led chemistry teams from hit-to-preclinical leads in three serotonin (5-HT1A, 5-HT2B, 5-HT6) programs

 Co-invented and developed novel and orally-active clinical candidates:

- Selective non-azaspirone-based 5-HT1A agonist PRX00023 for GAD and depression (Phase 3A)

- First-in-class thienopyrimidine-based 5-HT2B antagonist PRX-08066 for PAH (COPD) (Phase 2A)

- Potent quinoxazolone-based 5-HT4 agonist PRX-03140 for Alzheimer's disease (Phase 2B with GSK)

- Novel aryl piperazine-based 5-HT6 antagonist PRX-07034 for obesity and schizophrenia (Phase 2A)

 Contributed critically in joint Amgen-EPIX team efforts to develop highly selective S1P1 agonist

 Involved in Epix-GSK discovery programs (CEEDD) for novel anti-psychotic and anti-obesity agents

Research Fellow, University of Nebraska Medical Center, Omaha, NE 06/98-09/02

(Supervisor: Prof. Jonathan Vennerstrom)

 Worked on Hoffmann-La Roche / WHO / Medicines for Malaria (MMV) projects

 Involved in lead optimization of RBX-11160, an orally active synthetic trioxolane

 Worked on design and synthesis of chloroquine bioisosteres to counter drug resistance problems

 Performed lead optimization of orally active 2H-pyrroles as novel heme polymerization inhibitors

 Devised and prepared multi-step synthesis of peptide-based vaccine constructs for nicotine abuse

 Designed and synthesized novel prodrugs for creatine, a nutrient to improve poor bioavailability

 Synthesized benzoylaminosulfonyl glycines (BAPSG) as Aldose Reductase Inhibitors for diabetes

Postdoctoral Research Associate, National Tsing Hua University, Taiwan 01/97-05/98

(Advisor: Prof.Y.K.Lai)

 Designed and synthesized radiolabled and fluorescent conjugated analogs of the anticancer natural product paclitaxel (Taxol®) used as biological probes for secondary target elucidation

 Prepared the paclitaxel from its natural precursor, baccatin III using reported semi-synthetic route

Scientist, Indian Institute of Chemical Technology (IICT), Hyderabad, India 06/95 - 02/96

 Designed and synthesized novel bio-active molecules in collaboration with Dupont, Inc. USA.

 Supervised 3 PhD students, monitored work progress and reviewed the performance goals

 Synthesized aminoperhydroacridines as novel analogues of Tacrine (THA) and AChE inhibitors

Researcher, Indo-French joint project, Universte Rene Descartes, Paris, France 05/94 - 04/95

 Prepared novel anticancer pentacyclic indoloquinolines as Topoisomerase I and II inhibitors

EDUCATION

Ph.D. (Organic Chemistry), 1994, North-Eastern Hill University, Shillong, India

(Advisor: Prof. H. Junjappa; Thesis: Synthetic Studies on β-oxodithioacetals)

 Developed novel chemo and regio-selective reductions of conjugated systems with hydride agents

 Devised new synthetic methods for polyaromatics and fused heterocyclics via cycloaromatization of easily accessible acyclic 3-carbon synthons

AWARDS & RECOGNITION

 Recipient of Predix Star Performance awards 3 times in successive years (2003-2006)

 Member of UNMC research group award, “Most successful antimalarial team of year 2002” from 12 international projects funded by Medicines for Malaria Venture (MMV), a branch of WHO, Geneva

MEMBERSHIPS, CERTIFICATIONS, ADDITIONAL TRAINING

 Member of the American Chemical Society

 Completed training in GxP (May 2004), laboratory safety (2003-2008 annually), and radiochemical and hazardous material safety (2008)

PATENTS

1. Burli R; Cee VJ; Golden J; Lanman BA; Neira S; Saha A; Schutz N; Yu X; Mccauley D; Lobera, Mercedes; Marantz, Yael; Lin, Jian; Cheruku SR; Orbach P; Sharadendu A; Penland RC; Gannon K; Shacham S; Noiman S; Becker O; Zhang Z. Benzofurans and related compounds as S1P receptor modulators and their preparation, pharmaceutical compositions and use in the treatment of autoimmune and related immune diseases. U.S. Pat. Appl. Publ. (2008), 125pp, US2008027036 A1

2. Saha A; Yu XY; Lobera M; Lin J; Cheruku SR; Becker O; Marantz Y; Schutz N; Burli R; Cee VJ; Golden J; Lanman BA; Neira S. Benzofurans and related compounds as S1P receptor modulators and their preparation, pharmaceutical compositions and use in the treatment of autoimmune and related immune diseases. PCT Int. Appl. (2007), 270pp. WO 200-***-**** A2

3. Saha A; Yu XY; Lobera M; Lin J; Cheruku SR; Becker OM; Marantz Y; Schutz N. Preparation of S1P receptor modulating compounds in particular aryl-substituted 2-oxoimidazolidine derivatives as modulator of S1P receptor. PCT Int. Appl. (2007), 88pp. WO 200-***-**** A2

4. Saha AK; Sharadendu A; Yu XY; Lin J; Lobera M; Cheruku SR; Orbach P; Shacham S; Noiman S; Becker O; Marantz Y; Schultz N; McCauley D. Preparation of benzofuranylbenzylazetidine-carboxylates and related compounds as sphingosine-1-phosphate (S1P) receptor modulators. PCT Int. Appl. (2007), 130pp. WO 200-***-**** A2

5. Dhanoa DS; Becker O; Noiman S; Reddy SA; Cheruku SR; Melendez RE; Sharadendu A; Chen D; Marantz Y; Shacham S; Heifetz A; Inbal B; Kesavan V; Bar-Haim S. Piperidinylamino-thieno[2,3-d]pyrimidine compounds. U.S. 7,030,240 B2 (2006).

6. Becker O; Lobera M; Melendez RE; Sharadendu A; Wu L; Yu XY; Dhanoa DS; Cheruku SR; Marantz Y; Noiman S; Fichman M; Senderowitz H; Shacham S; Saha A; Orbach P. Preparation of piperazinylarylamines as 5-HT6 modulators. PCT Int. Appl. (2006), 169pp. WO 200-***-**** A1

7. Dhanoa DS; Becker O; Noiman S; Reddy SA; Cheruku SR; Melendez RE; Sharadendu A; Chen D; Marantz Y; Shacham S; Heifetz A; Inbal B; Kesavan V; Bar-haim S. Preparation of piperidinylamino-thieno[2,3-d]pyrimidine compounds as 5-HT2B modulators. U.S. Pat. Appl. Publ. (2005), 73 pp., US 200-***-**** A1

8. Cheruku SR; Becker O; Saha A; Noiman S. 5-HT4 Modulating Compounds and uses thereof. U.S. Pat. Appl. (2005)

9. Becker O; Melendez RE; Sharadendu A; Marantz Y; Fichman M; Lobera M; Senderowitz H; Cheruku SR; Noiman S; Yu XY; Shacham S; Wu L; Saha A; Orbach P; Dhanoa DS. Substituted Arylamine compounds and methods of treatment. U.S. Pat. Appl. (2005)

10. Dhanoa DS; Becker O; Noiman S; Cheruku SR; Marantz Y; Shacham S; Heifetz A; Inbal B; Kesavan V; Bar-haim S; Reddy SA; Melendez RE; Sharadendu A; Chen D. Preparation of piperidinylamino(benzo)thienopyrimidines as serotonin 5-HT2 receptor ligands. PCT Int. Appl. (2004), 39 pp., WO 200-***-**** A2

11. Dhanoa DS; Noiman S; Becker O; Marantz Y; Chen D; Shacham S; Inbal B; Bar-Haim S; Heifetz A; Cheruku SR; Mohanty P; Sharadendu A. Preparation of piperazinylindoles as serotonin modulating compounds. PCT Int. Appl. (2004), 39 pp. WO 200-***-**** A2

12. Dhanoa DS; Chen D; Becker O; Noiman S; Cheruku SR; Marantz Y; Sharadendu A; Shacham S; Heifetz A; Mohanty P; Inbal B; Fichman M; Nudelman R; Bar-Haim S. Preparation of arylpiperazinyl sulfonamides as 5-HT, in particular 5-HT1, receptor agonists and antagonists for treating CND disorders, especially anxiety and related diseases. PCT Int. Appl. (2004), 125 pp. WO 200-***-****

13. Becker O; Chen D; Cheruku SR; Dhanoa DS; Heifetz A; Kalid O; Kesavan V; Marantz Y; Mohanty P; Noiman S; Nudelman R; Shacham S; Sharadendu A. Preparation of substituted aminopyrimidines as Neurokinin antagonists effective for treating CNS disorders. PCT Int. Appl. (2004), 70 pp. WO 200-***-**** A2

14. Becker O; Chen D; Cheruku SR; Dhanoa DS; Heifetz A; Kalid O; Kesavan V; Marantz Y; Mohanty P; Noiman S; Nudelman R; Shacham S; Sharadendu A. Preparation of substituted aminopyrimidines as neurokinin antagonists effective for treating CNS disorders. US Pat. Appl. (2004)

15. Inbal B; Bar-Haim S; Heifetz A; Cheruku SR; Mohanty P; Sharadendu A. Preparation of piperazinylindoles as serotonin modulating compounds. PCT Int. Appl. (2004), 39 pp. WO 200-***-**** A2

16. Dhanoa DS; Cheruku SR; Becker O; Noiman S. New Piperazinyl Sulfanyl Hydrazide Compounds. US Pat. Appl. (2003)

17. Sanderson SD; Vennerstrom JL; Cheruku SR and Padmanilayam MP. Compositions and Compounds for Use as a Nicotine Vaccine Employing Response Selective Agonist of an Antigen-Presenting Cell Receptor as a Molecular Adjuvant. PCT Int. Appl. (2003), 63168PCT

18. Sanderson SD; Vennerstrom JL; Cheruku SR and Padmanilayam MP. Compositions and Compounds for Use as a Nicotine Vaccine Employing Response Selective Agonist of an Antigen-Presenting Cell Receptor as a Molecular Adjuvant. US Pat. Appln. (2002) (Ser # 60.360,967).

19. Iyengar DS; Nagubandi L; Cheruku SR; Ganta SR and Gobburu H. A Process for the Synthesis of New Aziridinyl Compound As a Potential Agro Compound. Indian patent (1996).

20. Iyengar DS; Nagubandi L; Gobburu H; Cheruku SR and Ganta SR. A Process for the Synthesis of Bis-N-Aryl Cinnamic Acid Derivatives as Potential Anti-tumor Agent. Indian patent (1996).

PUBLICATIONS

1. Dong Y; Tang Y; Chollet J; Matile H; Wittlin S; Charman SA; Tomas JS; Scheurer C; Cheruku SR; Snyder C; Scorneaux B; Bajpai S; Alexander SA; Wang X; Padmanilayam MP; Brun R and Vennerstrom JL. Effect of Functional Group Polarity on the Antimalarial Activity of Spiro and Dispiro-1,2,4-Trioxolanes. Bioorganic Med Chem (2006), 14, 6368-6382.

2. Becker O; Dhanoa DS; Marantz Y; Chen D; Shacham S; Cheruku SR; Heifetz A; Mohanty P; Fichman M; Sharadendu A; Nudelman R; Kaufmann M and Noiman S. An Integrated In Silico 3D Model-driven Discovery of a Novel, Potent and Selective Aminosulfonamide 5-HT1A Agonist (PRX-00023) for the Treatment of Anxiety and Depression. J Med Chem. (2006), 49 (11), 3116 -3135.

3. Sunkara G; Ayalasomayajula SP; Cheruku SR; Vennerstrom JL; DeRuiter J and Kompella UB. Systemic and ocular pharmacokinetics of N-4-benzoylaminophenylsulfonylglycine (BAPSG), a novel aldose reductase inhibitor. J Pharmacy and Pharmacol. (2004), 56(3):351-8

4. Cheruku SR; Maiti S; Dorn A; Scorneaux B; Bhattacharjee AK; Ellis WY and Vennerstrom JL. Carbon Isosteres of the 4-Aminopyridine Substructure of Chloroquine: Effects on pKa, Hematin Binding, Inhibition of Hemazoin Formation and Parasite Growth. J. Med. Chem. (2003), 46, 3166-3169.

5. Cheruku SR; Padmanilayam MP and Vennerstrom JL. Synthesis of 2H-Pyrroles by Treatment of Pyrrolidines with DDQ. Tetrahedron Lett. (2003), 44, 3701-3703.

6. Sanderson SD; Cheruku SR; Padmanilayam MP; Vennerstrom JL; Thiele GM; Palmatier MI and Bevins RA. Immunization to Nicotine with a Peptide-based Vaccine Composed of a Conformationally Biased Agonist of C5a as a Molecular Adjuvant. Intl. Immunopharmacology. (2003), 3, 137-146.

7. Chu JJ; Chiang CD; Rao CS; Chang WM and Lai YK. Establishment and Characterization of a Paclitaxel-Resistant Human Non-Small Cell Lung Cancer Cell Line. Anticancer Research (2000), 20(4), 2449-2456.

8. Madhushaw R; Cheruku SR; Narkunan K; Lee GH; Peng SM and Liu RS. New Carbonyl Reaction of Tungsten-Propargyl Compounds via Protonation at a Prolonged Period. Organometallics (1999), 18, 748-752.

9. Rao CS; Chu JJ; Liu RS and Lai YK. Synthesis and Evaluation of [C-14]-Labeled and Fluorescent Tagged Taxol Derivatives as New Biological Probes. Biorganic Medicinal Chemistry (1998), 6, 2193-2204.

10. Rao CS; Patro B; Ila H and Junjappa H. Chemoselective Conjugate 1,4-Reduction of α-Oxoketene Dithioacetals with Zinc in Acetic Acid: Synthesis of ß-oxodithioacetals. Indian Journal of Chemistry (1996), 35B, 57-59.

11. Junjappa H; Ila H; Patro B and Rao CS. Heteroaromatic Annelations for the Synthesis of Bridge-head Nitrogen Compounds via a-Oxoketene Dithioacetals. Journal of Indian Chemical Society (1994), 71, 501-507, (Review).

12. Rao CS; Malapaka C; Patro B; Ila H and Junjappa H. Facile One-pot Thermal Dehydration and Dethioacetalization of ß-Hydroxydithioacetals with Dimethyl Sulphoxide: Synthesis of a ß-Unsaturated Aldehydes. Tetrahedron (1994), 50, 5783-5794.

13. Rao CS; Chakrasali RT; Ila H and Junjappa H. Cyclocondensation of α- Hydroxyimino- ß-Alkyl/Arylimino-ß-Methylthioketones with Hydrazine Hydrate: Synthesis of 3(5)-Aryl-5(3)-Alkyl/Aryl-imino-4-Nitroso (or amino) Pyrazoles. Journal of Heterocyclic Chemistry (1993), 30, 129-134.

14. Rao CS; Malapaka C; Ila H and Junjappa H. Deprotection of Thioacetals and 1,3-Dithianes with Dimethyl sulphoxide. Tetrahedron Letters (1992), 33(52), 8163-8164.

15. Rao CS; Singh OM; Ila H and Junjappa H. A New General Route to 1,2-Diarylethylenes, 1,4-Diaraylbutadienes and 1,6-Diarylhexatrienes through Cycloaromatization of ß-Oxodithioacetals. Synthesis (1992), (11): 1075-1077.

16. Rao CS; Balu MP; Ila H and Junjappa H. Cycloaromatization of α-Oxoketene Dithioacetals and ß-Oxodithioacetals with Benzyl, 1-Naphthylmethyl and 2-Naphthylmethylmagnesium Halides: Synthesis of Condensed Polynuclear Aromatic Hydrocarbons. Tetrahedron (1991), 47(20/21): 3499-3510.

17. Rao CS; Chakrasali RT; Ila H and Junjappa H. Regio- and Chemoselective Conjugate 1,4-Reduction of α -Oxoketene Dithioacetals with Sodium Borohydride and Sodium Cyanoborohydride. Tetrahedron (1990), 46(6): 2195-2204.

PRESENTATIONS

1. Dhanoa DS; Becker O; Chen D; Cheruku SR; Shacham S; Marantz Y; Heifetz A; Mohanty P; Fichman M, Sharadendu A; Nudelman R; Kaufmann M and Noiman S. Discovery of potent, selective and orally active 5-HT1A agonist, PRX-00023, for the treatment of anxiety, depression and attention deficit hyperactivity disorder. First-time Clinical Disclosure Abstracts of Papers, 229th ACS National Meeting, San Diego, CA, United States, March 13-17, 2005 (2005).

2. Cheruku SR; Padmanilayam MP and Vennerstrom JL. Convenient method for the synthesis of 2H-pyrroles from Pyrrolidines and Pyrrolines. Book of Abstracts (2002), # 346, April 2002 ACS National Meeting, Orlando, Florida.

3. Padmanilayam MP; Cheruku SR; Vennerstrom JL and Sanderson SD. Nicotine Vaccine using a Response-selective Agonist of Human C5a as a Molecular Adjuvant. Book of Abstracts (2002), # 50, April 2002 ACS National Meeting, Orlando, Florida.

4. Sunkara G; Ayalasomayajula SP; Cheruku SR; Jonathan LV and Kompella UB. Pharmacokinetics of benzoylamino-sulfonylglycine (BAPSG) following intravenous, intraperitoneal, subcutaneous, and oral dosing in rats. Book of Abstracts (2001), # T3328, AAPS Annual Meeting, October 21-25, 2001, Denver, Colarado.

5. Gwilt PR; Wall DA; Shenoy S; Manouilov KK; Cheruku SR and Gordon BG. Population pharmacokinetics of Etoposide and Thiotepa in children undergoing high-dose chemotherapy for the Pediatric Blood and Marrow Transplant Consortium. Book of Abstracts (2000), # 1683, American Society of Hematology, 42nd Annual Meeting (December 1-5, 2000) at San Francisco, California.

6. Cheruku SR; Ila H and Junjappa H. Synthesis of Stilbenes and Terminally Substituted Polyenes from α –Oxodithioacetals. Book of Abstracts (1991), # P-24, The Royal Society of Chemistry Symposium, December 5-7, 1991, India.

Contact this candidate