Head, URDIP (Dr. R.R. Hirwani- till and Prof. Nangia from ) Lakhs

Transcription

1 1. Project Title: Chembioinformatics For Drug Discovery 2. Project Details: Nodal Lab Participating Labs Nodal Officer Taskforce Chairman Total Man Days Approved Cost CSIR-URDIP Output used by CSIR labs involved in drug discovery Sivakami Dhulap Head, URDIP (Dr. R.R. Hirwani- till and Prof. Nangia from ) Lakhs Fund received Fund utilized Lakhs Lakhs 3. Periodic Key Recommendations of Task Force/RC/Monitoring Committee S.No Key Recommendations of Task Action taken on Key Recommendations Proposed Revised Force/RC/ Monitoring Deliverabl Deliverable Committee (approved es by Task Force) TFM About creation of virtual 1.As suggested, the All the libraries- consider additional following medicinal aspects were recommendations were medicinal chemistry aspects pertaining to improve the considered to be included into the and collate initial list of Indian strategies, methods and database: toxic plants outcomes of the project Pre-formulation solubility data for the and to meet the molecules in the Gl tract envisaged objectives. Polymorphic data for the molecules e.g. Alpha, beta crystalline form Microsomal stability (Liver) Cytochrome P450 herg liability - Heart Rate 2. A list of 232 Indian toxic plants of Indian origin was collated 2nd TFM Consideration of clinically New uses of known molecules were validated targets, new use of explored for specific therapeutic areas known drugs, validation of the such as bacterial infections and the molecules at 111M-Jammu results were validated at 111M-Jammu.

2 3rd TFM 4th TFM 51h TFM RC Meeting 2013 RC Meeting 2014 RC Meeting 2016 Repositioning of the newly designed derivatives, focus on natural products Evaluation combinations pathways. of synergistic to specific Approval to hire the required project staff at lower level to get the work done Clustering of scaffolds to be included into the database, explore synergistic combinations and incorporate in proposed predictive model AC was appreciative of the work done by CSIR-URDIP on OSDD projects through I lim The RC committee appreciated the contributions provided to few of the drug discovery programmes for specific labs. AC was appreciative of the work done by CSIR-URDIP to support the drug discovery projects of I lim, CDRI and IICT New uses of known molecules were explored for therapeutic areas such as Alzheimer's disease and cancer and the results were validated at 111M Jammu. New use of bioactives from medicinal plants were explored and shared with CSIR scientists as an additional improvement to their existing inventions which also satisfied the required parameters for IP protection. Experimentally validated combinations were designed and presented. The work is now being considered for publication. The work related to clustering the scaffolds has been initiated and in progress. The model required to predict the synergistic effect is also initiated. The committee suggested that this work should be extended to other drug discovery projects of CSIR. They recommended that this capability should be made known to all the chemical and biology cluster labs within CSIR so that they can also take advantage of URDIP expertise The committee suggested that capability can be built in for downstream drug development stages. 4. Project Achievements: 1. DELIVERABLES: Envisaged WP1: Create a Database of Deliverables The objective as envisaged for the work package is achieved. Further as per Evaluation Report -CBDD ISC0203 Pg2

3 Therapeutic Molecules in Public Domain: WP2: Lead Optimization for selected therapeutic targets WP3: Phytochemical Fragment Based Drug Discovery Development WP4: Capability building in T oxinformatics (Predictive Toxicology & QSAR) the initial proposal the number of molecules to be included for each of the proposed therapeutic area was not anticipated. However the analysis revealed that there are quite a number of molecules relevant to be included into the proposed database for each of the proposed therapeutic areas. Hence based on the recommendations of the Task Force, it was decided to compile 100 molecules for each of the therapeutic areas namely cancer, tuberculosis, malaria and Leishmaniasis. Based on this recommendation the work was initiated and has been completed. The creation of virtual libraries, screening of hits and lead optimization strategies for the conversion of hits to lead were carried out for the targets which were of focus by scientists at CSIR-IIIM, CSIR-IICT, CSIR-CDRI and CSIR-CIMAP. The virtual libraries as well as the outcomes from the in-silica work were shared with the scientists working on the specified targets and disease conditions. Few of the inputs were validated and used not only to compliment the efficacy but also the IP component created from the R&D. As proposed, active fragments from the bioactives were enlisted. Using the FBDD approach new lead compounds was designed and their activity was predicted. As envisaged, the team has developed methodologies to make a preliminary judgment about safety, toxicology assessment for early screening out of candidate molecules bas-ed on available literature as well as predictive tools. Apart from the proposed work, the team has also developed a methodology and a prototype to build newer predictive models specifically to predict herg toxicity and synergistic effects of drugs for a given pathway. The models has been appreciated by experts and commented to be unique and useful for some of the programmes as prioritized by the President of CSIR. Further as per the recommendations of Task Force, the work was initiated on creating a list of toxic plants to be studied in detail at a later date in the next phase of the proqramme. 5. Outcomes and outputs from the projects: a. Outcomes The main outcome from the project was in the form of information products containing database and libraries of compounds along with their physio-chemical and pharmacological parameters. The delivery of such kind of chemical information facilitated the application of computational tools and filters to identify and analyze active sites on the target protein and to select and design potential drug molecules for the therapeutic areas under consideration at the sister labs. This data was of potential importance for CSIR Evaluation Report - CBDD /SC0203 Pg3

4 labs and other drug discovery programmes during the term of the project wherein URDIP team provided the critical information. The in-silica approaches and the results obtained during the project provided assistance in decision making in terms of selecting the preferred ligands for a specific target. This in turn reduced the cost and time required in the R&D at the initial stages of the drug development process. CSIR-URDIP has worked on hundreds of molecules and successful examples of potential leads taken up for optimization and development of pre-clinical candidates for different diseases. This has led to increase in number of invention disclosures and number of patent filings. While working on this programme, we have developed strategies for the development of potentially new hits (60+) and new uses (12) of known compounds as well as their validations. In addition, methodology to assess safety profiles for bioactives, extracts and small molecule organic compounds using in-silica approaches has been developed. These strategies and methodologies will be useful in all drug discovery programmes. Table 1 enlists the newly designed hits and the therapeutic areas: Table 1 :List of Predicted and Validated New Use of Known Compounds Drug Name Predicted MOA Predicted New Use Validation -lnvitro 1. URDNU01 Nor A Efflux pump inhibitor Bacterial infection -S.Aureus Yes 2. URDNU02 Nor A Efflux pump inhibitor Bacterial infection - S.Aureus Yes-Most Potent 3.URDNU03 Nor A Efflux pump inhibitor Bacterial infection - S.Aureus Yes 4.URDNU04 Nor A Efflux pump inhibitor Bacterial infection -S.Aureus Yes-Most Potent 5.URDNU05 Nor A Efflux pump inhibitor Bacterial infection -S.Aureus Yes 6.URDNU06 Nor A Efflux pump inhibitor Bacterial infection -S.Aureus Yes-Most Potent Evaluation Report -CBOO ISC0203 Pg4

5 7.URDNU07 Pgp activators Alzhimer's disease Yes-Most Potent 8.URDNU08 Pgp activators Alzhimer's disease Yes-Most Potent 9.URDNU09 Pgp activators Alzhimer's disease Yes 10.URDNU10 Pgp activators Alzhimer's disease Yes 11.URDNU11 Pgp activators Alzhimer's disease Yes 12.URDNU12 CYPB1 Cancer-Breast Cancer Yes- Most Potent /Chemoprevention 13.URDNU13 CYPB1 Cancer-Breast Cancer Yes- Most Potent /Chemoprevention 14.URDNU14 CYPB1 Cancer-Breast Cancer Yes - Moderate to /Chemoprevention high 15.URDNU15 CYPB1 Cancer-Breast Cancer Yes- Moderate to /Chemoprevention high 16.URDNU16 mtor- Cancer-Colon/Melanoma Yes-Potent Table 2: New Designs, predicted Mechanism of Action and Therapeutic Area Table 2: New Desians, predicted Mechanism of Action and Therapeutic Area Structure Codes Therapeutic Target Therapeutic Area URDND01 Cyclin-dependent Kinase-2 Cancer- Non-small cell lung cancer (CDK-2) (NSCLC), Advanced breast cancer URDND02 Cyclin-dependent Kinase-2 Cancer- Non-small cell lung cancer URDN003 (CDK-2) (NSCLC), Advanced breast cancer Cyclin-dependent Kinase-2 Cancer- Non-small cell lung cancer UROND04 (NSCLC), Advanced breast cancer Cyclin-dependent Kinase-2 Cancer- Non-small cell lung cancer (CDK-2) (NSCLC), Advanced breast cancer (CDK-2) Evaluation Report -CBDD /SC0203 Pg5

6 URDND05 Cyclin-dependent Kinase-2 Cancer- Non-small cell lung cancer (CDK-2) (NSCLC), Advanced breast cancer URDND06 Phosphatidylinositol-3 kinases Leukemia and Lymphoma (P13K) URDND07 Phosphatidylinositol-3 kinases Leukemia and Lymphoma (PI3K) URDND08 Phosphatidylinositol-3 kinases Leukemia and Lymphoma (PI3K) URDND09 Phosphatidylinositol-3 kinases Leukemia and Lymphoma (PI3K) URDND10 Phosphatidylinositol-3 kinases Leukemia and Lymphoma (PI3K) URDND11 Phosphatidylinositol-3 kinases Leukemia and Lymphoma (PI3K) URDND12 Phosphatidylinositol-3 kinases Leukemia and Lymphoma (PI3K) URDND11 Mammalian target of rapamycin Breast cancer, Hepatocellular (mtor) carcinoma, Sarcoma URDND12 Mammalian target of rapamycin Breast cancer, Hepatocellular (mtor) carcinoma, Sarcoma URDND13 Mammalian target of rapamycin Breast cancer, Hepatocellular (mtor) carcinoma, Sarcoma URDND14 Mammalian target of rapamycin Breast cancer, Hepatocellular (mtor) carcinoma, Sarcoma URDND15 Mammalian target of rapamycin Breast cancer, Hepatocellular (mtor) carcinoma, Sarcoma URDND16 Epidermal growth factor receptor Lung Cancer, Colon Cancer (EGFR) URDND17 Epidermal growth factor receptor Lung Cancer, Colon Cancer (EGFR) URDND18 Epidermal growth factor receptor Lung Cancer, Colon Cancer (EGFR) URDND19 Epidermal growth factor receptor Lung Cancer, Colon Cancer (EGFR) URDND20 Thymidylate Synthase inhibitor Anti-cancer URDND21 Thymidylate Synthase inhibitor Anti-cancer URDND22 Thymidylate Synthase inhibitor Anti-cancer URDND23 Thymidylate Synthase inhibitor Anti-cancer URDND24 Thymidylate Synthase inhibitor Anti-cancer URDND25 Thymidylate Synthase inhibitor Anti-cancer URDND26 Thymidylate Synthase inhibitor Anti-cancer Evaluation Report -CBDD /SC0203 Pg6..

7 UROND27 Thymidylate Synthase inhibitor Anti-cancer URON030 HIV -Reverse transcriptase inhibitor Anti-virai/Anti-HIV UROND31 URON032 URON033 HIV -Reverse transcriptase inhibitor Anti-virai!Anti-H IV HIV -Reverse transcriptase inhibitor Anti-virai/Anti-H IV HIV -Reverse transcriptase inhibitor Anti-viral/ Anti-H IV URON034 HIV -Reverse transcriptase inhibitor Anti-viral/ Anti-H IV URDN035 HIV -Reverse transcriptase inhibitor Anti-viral/ Anti-H IV Promising technology I product leads for further translation will be proposed by respective labs. We spotted a short window of opportunity in the area of toxinformatics and undertook technical services contract leading to External cash Flow of Rs.400 lakhs during the period under review. Based on work done by us, IICT has signed an MoU with Dortmund University, North Rhine-Westphalia, Germany for collaborative research on cancer drugs targeting cancer stem cells Database: 1 Therapeutically Active molecules in public domain Virtual Libraries: 6 Virtual Libraries consisting of the following type of compounds were created: Phytochemical Library bioactives Library of FDA approved molecules molecules Pgp inhibitors- 80+ synthetic molecules Boswellic Acid Library CDK-2 inhibitors molecules Nor A Efflux pump inhibitors These libraries can be shared with teams working on drug discovery in Structure Data File (SDF) formats. b. Outputs: Periodic Reports Submitted: The technical reports summarizing the data and inputs from the in-silica studies on the following topics were submitted to the labs: 1. Library of medicinal plants, bioactives and pharmacological aspects effective against Oral cancer, Malaria, hepatitis (CSIR-NEIST) Evaluation Report - CBDD ISC0203 Pg 7

8 2. Library of bioactives and small molecules as therapeutics against liver and oral cancer specifically by targeting cancer stem cells (CSIR-IICT) 3. Scaffolds effective as Advanced Glycation End Product (AGE) Inhibitors in Diabetes (CSIR-I IIM) 4. Drug and Target evaluation on An Anti-osteoporotic compound (CSI R-CDRI) 5. Drug and Target evaluation on An Anti-thrombotic compound (CSIR-CDRI) 6. Drug and Target evaluation on An Anti-malarial compound (CSIR-CDRI) 7. Drug Evaluation Report on Centbucridine (CSIR-CDRI) 8. Anti-TB -pipeline and patent search on TB patents (CSIR-HQ) 9. Chemical and Pharmacological evaluation of Mahanimbine and its derivatives. (CSIR-IIIM) 10. Target evaluation- PCSK 9 (CSIR-CDRI) 11. Target evaluation GLP-1 R (CSIR-CDRI) 12. Synthetic modification and pharmacology evaluation of Cannabidiol. (CSIR-IIIM) 13. Scaffold library of molecules active against Gram Positive Bacteria (OSDD) 14. Antitubercular activity of around 300 molecules (CSIR-NCL) 15. PA-824 drug portfolio (OSDD) Further, as proposed, unique in-silico and SAR based approaches to screen the virtual libraries, selection & optimization of hits etc. have been developed and documented in the form of reports I publications and are listed below: 1. Pharmacophore based Virtual Screening and Docking Studies for P-glycoprotein (Pgp) Activators - bioactives 2. Docking Studies for P-glycoprotein (Pgp) and Pregnane X receptor (PXR) Activators-bioactives 3. Lead discovery for PXR activators for the treatment of Alzheimer's disease (screening multiple libraries) 4. Proposed Herbal formulations for treating and preventing the onset of Alzheimer's Disease based on MOA 5. Proposed Herbal formulations for treating and preventing Inflammation based on MOA of medicinal plants 6. Proposed Herbal formulations for treating and preventing diabetes type-ii on MOA of medicinal plants 7. Proposed Herbal formulations for treating and preventing Obesity based on MOA of medicinal plants 8. Pharmacophore development and 3D QSAR analysis to combat resistance due to NorA efflux pump 9. A hybrid docking and FBDD approach to design semi-synthetic Selective mtor inhibitors 10. A hybrid docking and FBDD approach to design semisynthetic CDK2 inhibitors Evaluation Report -CBDD ISC0203 Pg8

9 11. Structure-Based Design of Class-1 Phosphatidylinositol-3 kinases (PI3K) Inhibitors as Anti-cancer Agents 12. E-Pharmacophore Modelling Combined with High-Throughput Virtual Screening and Docking to Identify Potential Inhibitors of Class-1 Phosphatidylinositol-3 kinases (PI3K) 13. Prior Art and SAR for TNF-alpha inhibitors 14. In-silica knowledge based approach for Repositioning of Drug 15. Structure-Based Design of Cyclin-Dependent Kinase 2 (CDK-2) Inhibitors as Anti-cancer Agents 16. Repositioning of Anti-cancer Agents as Cyclin-Dependent Kinase 2 (CDK2) Inhibitors 17. Homology Modeling and lnsilco Structural Analysis of Caseinolytic Protease P2 (CipP2): Mycobacterium Tuberculosis 18. Pharmacophore development and 3D QSAR analysis to combat resistance due to NorA efflux pump 19. A hybrid docking and FBDD approach to design semi-synthetic Selective mtor inhibitors Publications i. Total number - 24 ii. Cumulative IF (as per 2015 figures): iii. Average IF: iv. Average IF/scientist Publications -Details: The published papers from in-house studies as well as in-association with researchers from academia are enlisted below: 1. Sivakami, D. and, Abhijeet, D. "Pharmacophore based virtual screening of natu ral product database to identify potential lead Cyclooxygenase-2 inhibitors (COX-2)." Journal of Computational Methods in Molecular Design 3, no.4 (2013): Pravin, S. Nikhil, V. Sivakami, D. Abhijeet, D. and, Raj, H. "Pharmacophore development and molecular docking studies for dual acting leads from natural products for P-glycoprotein (Pgp) and Pregnane X Receptor (PXR) activation for the improved ~-amyloid clearance in Alzheimer's disease." Central Nervous System Agents in Medicinal Chemistry 16 (2016): Anita, M. Sivakami, D. Abhijeet, D. and, Satish, B." Review on the anticancer and in-silica binding studies of phenanthroindolizidine alkaloids."chemicallnformatics 1, no.1 :5 (2015): Evaluation Report -CBDD ISC0203 Pg9

10 4. Archana, P. Anushree, V. Veena, D. and, Raj, H."Evaluation of Potential Toxicity of Bioactives of Anagallis arvensis- A Toxic Plant International Journal of Toxicological and Pharmacological Research 8, no.3 (2016): Nazreen, Syed. Mohammad Sarwar, Alam. and, Abhijeet, D."Thiazolidine-2,4-diones derivatives as PPAR-c agonists: Synthesis, molecular docking, in vitro and in vivo antidiabetic activity with hepatotoxicity risk evaluation and effect on PPAR-c gene expression." Bioorganic & Medicinal Chemistry Letters 24 (2014): Saqlain, Haider. Mohammad Sarwar, Alam. and, Abhijeet, D."Synthesis of novel 2-mercaptobenzoxazole based 1,2,3-triazoles as inhibitors of proinflammatory cytokines and suppressors of COX-2 gene expression."european Journal of Medicinal Chemistry 81 (2014): Chetna, Kharbanda. Mohammad Sarwar, Alam. and, Abhijeet, D."Synthesis and evaluation of pyrazolines bearing benzothiazole as anti-inflammatory agents." Bioorganic & Medicinal Chemistry 22, no.21 (2014): Chetna, Kharbanda. Mohammad Sarwar, Alam. and, Abhijeet, D."Novel benzenesulfonylureas containing thienylpyrazoline moiety as potential antidiabetic and anticancer agents." Bioorganic & Medicinal Chemistry Letters 24, no.22 (2014): Nazreen, Syed. Mohammad Sarwar, Alam. and, Abhijeet, D. "Design, synthesis, in silica molecular docking and biological evaluation of novel oxadiazole based thiazolidine-2,4-diones bis-heterocycles as PPAR-y agonists." European Journal of Medicinal Chemistry no.87 (2014 ): Saqlain, Haider. Mohammad Sarwar, Alam. and, Abhijeet, D. "Design, synthesis and docking studies of 2- benzoxazolinone-based 1,2,4-triazoles as proinflammatory cytokine inhibitors." Medicinal Chemistry Research 23, no.9 (2014): Sameena, Bano. Mohammad Sarwar, Alam. and, Abhijeet, D "Synthesis, biological evaluation and molecular docking of some substituted pyrazolines and isoxazolines as potential antimicrobial agents." European. Journal of Medicinal Chemistry no.95 (2015): Nazreen, Syed. Mohammad Sarwar, Alam. and, Abhijeet, D. "Design, Synthesis, and Biological Evaluation of Thiazolidine-2,4-dione Conjugates as PPAR-y Agonists." Archiv der Pharmazie (Weinheim, Germany) 348, no.6 (2015): Yakub, Ali. Mohammad Sarwar, Alam. and, Abhijeet, D. "Design, synthesis and biological evaluation of piperic acid triazolyl derivatives as potent anti-inflammatory agents." European Journal of Medicinal Chemistry 92 (2015): ~ Evaluation Report -CBDD ISC0203 Pg 10

11 14. Yakub, Ali. Mohammad Sarwar, Alam. and, Abhijeet, D. "Design and Synthesis of Butenolide-based Novel Benzyl Pyrrolones: Their TN F-a based Molecular Docking with In vivo and In vitro Anti-inflammatory Activity." Chemical Biology & Drug Design 86, no.4 (2015): Nazreen, Syed. Mohammad Sarwar, Alam. and, Abhijeet, D. "New flavone and phenolic esters from Callistemon lanceolatus DC: Their molecular docking and antidiabetic activities." Arabian Journal of Chemistry, Ahead of Print Journal Yakub, Ali. Mohammad Sarwar, Alam. and, Abhijeet, D. "Design and synthesis of butenolide-based amide derivatives as anti-inflammatory agents." Medicinal Chemistry Research 24, no.11 (2015): Chetna, Kharbanda. Mohammad Sarwar, Alam. and, Abhijeet, D. "Antidiabetic effect of novel benzenesulfonylureas as PPAR-y agonists and their anticancer effect." Bioorganic & Medicinal Chemistry Letters 25, no.20 (2015): Yakub, Ali. Mohammad Sarwar, Alam. and, Abhijeet, D. "Molecular modeling and synthesis of some new 2- imino-4-thiazolidinone derivatives with promising TNF-a inhibitory activity." New Journal of Chemistry 40, no.1 (2016): Tantray, Mushtaq A. lmran, Khan. Mohammad Sarwar, Alam. and, Abhijeet, D. "Synthesis of pyrimidin-4-one- 1,2,3-triazole conjugates as glycogen synthase kinase-3~ inhibitors with anti-depressant activity." Bioorganic Chemistry 68 (2016): Tantray, Mushtaq A. lmran, Khan. Mohammad Sarwar, Alam. and, Abhijeet, D. "Synthesis of benzimidazole based thiadiazole and carbohydrazide conjugates as glycogen synthase kinase-3~ inhibitors with antidepressant activity." Bioorganic & Medicinal Chemistry Letters 26, no.16 (2016): Chetna, Kharbanda. Mohammad Sarwar, Alam. and, Abhijeet, D. "Novel benzothiazole based sulfonylureas/sulfonylthioureas: design, synthesis and evaluation of their antidiabetic potential." New Journal of Chemistry 40, no.8 (2016): Chetna, Kharbanda. Mohammad Sarwar, Alam. and, Abhijeet, D. "Novel Piperine Derivatives with Antidiabetic Effect as PPAR-y Agonists." Chemical Biology & Drug Design 88, no.3 (2016): Tantray, Mushtaq A. lmran, Khan. Mohammad Sarwar, Alam. and, Abhijeet, D. "Synthesis of benzimidazolebased 1,3,4-oxadiazole-1,2,3-triazole conjugates as glycogen synthase kinase-3~ inhibitors with antidepressant activity in in vivo models." RSC Advances 6, no.49 (2016): Tantray, Mushtaq A. lmran, Khan. Mohammad Sarwar, Alam. and, Abhijeet, D."Synthesis of aryl anilinomaleimide based derivatives as glycogen synthase k i nase-3~ inhibitors with potential role as antidepressant agents." New Journal of Chemistry 40, no.? (2016): Evaluation Report -CBDD ISC0203 Pg 11

12 POSTER PRESENTATIONS: In addition to above papers, seven poster presentations were made at relevant conferences Chintamani, J. and, Sivakami, D. Natural product to natural product: A S. aureus NorA efflux pump inh ibitors (Recent Advances in Computational Drug Design held at lise Bangalore on Sep 16-17, 2013) Lakshmikant, D. and, Nishad, D. Fragment based design of novel cdk-2 inhibitors from natural scaffolds (Recent Advances in Computational Drug Design held at lise. Bangalore on Sep 16-17, 2013) Chetan, K. and, Sivakami, D. Patinformatics guided 3D-QSAR and Virtual screening for identification of selective CDK2 inhibitors (Recent Advances in Computational Drug Design held at lise. Bangalore on Sep 16-17, 2013) Pravin,S. and, Nikhil, V. Pharmacophore model for P-Giycoprotein Activators and Generation of Lead from Natural Products for Improved ~-amyloid Computational Drug Design held at lise. Bangalore on Sep 16-17, 2013) Clearance in Alzheimer's Disease (Recent Advances in Chintamani, J. In-silica designing of competitive NorA efflux pump inhibitors using pharmacophore and 3D QSAR approach. (Conference on Accelerating Biology Catalyzing Evolution organized by CDAC Pune on January 20-22, 2015). Omkar, P. and, Nishad, D.Bioactive Fragment based selective m-tor Inhibitors using FBDD approach (Conference on Accelerating Biology Catalyzing Evolution organized by CDAC Pune on January 20-22, 2015). Vikram, K. and, Shilpa, G. In-silica assisted pathway specific combination therapy: A case study (Conference on Accelerating Biology current trends in Bioinformatics and drug discovery organized by CDAC Pune on January 19-21, 2016). Patents (or other forms of IP generated such as Copyrights, Designs etc.) i. Filed -1 ii. Granted iii. Licensed iv. Copyrights : Filed -1 Human Resource generated i. PhD fellows (PhDs completed : 3 pursuing :2 ) ii. Project fellows: Evaluation Report -CBDD ISC0203 Pg 12

13 Skills imparted (Including skill set developed for technical services/ consultancy/ training purposes): as listed below: The therapeutically active molecule database is a valuable resource that can be reviewed by CSIR labs I scientist and used to invent around to either generate new derivatives or develop novel processes for new type of generic drugs or to develop new use for existing molecule to eventually provide health care at an affordable cost. Developed expertise on developing different unique in-silica methodologies which were useful in pred icting and providing inputs related to selection and optimizing hits Identification of pharmacophores and small molecule chemical entities which were bio-evaluated against pre-identified targets/cell lines for specific therapeutic categories i.e. Cancer, Alzheimer's disease and Bacterial infections. The methodologies were useful to provide key insights for R&D decision making in terms of selection of hits for a specific target. The compounds submitted as virtual libraries were useful in aligning the R&D focus of the 12 FYP projects at the sister laboratories Development and application of unique methodology using the available literature on chemical and biological activity as well as prediction tools for preparing safety assessment profiles of small molecules and phytoconstituents. Safety assessments studies were used to consider the screening of the molecules predicted for activities at the in-vitro level. External collaborations established: Procter and Gamble, USA on Toxinformatics studies. External collaborations established: A short window of opportunity was spotted in the area of toxinformatics and entered into a Technical Services agreement with a leading MNC from USA which led to lot of learning for our team and access to databases and tools as well as External cash Flow of Rs.400 lakhs during the period under review. The team collaborated with Jamia-Hamdard Deemed University, New Delhi and provided in-silica molecular interaction studies for their ongoing drug-discovery projects which led to the University signing an MoU with CSIR-URDIP to start PhD programme in Cheminformatics. Evaluation Report - CBDD ISC0203 Pg 13

14 6. Sectoral Monitoring Committee Recommendations on Lead/Technology/Product (listed above): For each Lead/Technology/Product provide details separately: Criteria SMC Recommendations Name of Lead/Technology /Product Is the Lead/ Technology/Product worth taking up further? What is the further R&D efforts that need to be put by CSIR/CSIR laboratories? Global benchmarking of the Lead/Technology/Product specifically wrl specifications and cost Is the Lead/Technology/Product worthy of commissioning a DPR at this stage? What are the likely resources and time duration required for taking forward the identified Lead/ Technology/Product to the desired TRL? Potential stake holders who may be appropriate to partner technically as well as financially Suggestion for plausible road map towards further development of lead/technology/product for achieving desired TRL GO/NO GO further development Other suggestions, if any, related to benefits/usage/ commercialization 7. Identified "lessons to be learnt", especially from shortcomings/failures. Evaluation Report -CBDD ISC0203 Pg 14

15 8. Comments on financial progress on the project fund availability and utilization of fund in the project: The financial progress was found satisfactory and investments made justified 9. Sectoral Monitoring Committee Recommendations on Facility creation or other outcomes: Excellent facility which can be used by other Agencies from industry, academia or research laboratories, start-ups, entrepreneurs, IP Service providers 10. Grading of Project Execution: Outstanding/ExcellentNery Good/Good/Satisfactory/Un-satisfactory Excellent 11. Additional comments, if any: Critical mass of staff must be ensured for effective delivery of services Continuity of the project should be ensured for services to stakeholders In the future versions of this service, the following may be considered: - Automation of data mining and analytics should be explored - Providing drug discovery service to pharmaceutical companies should be explored - Training courses should be pursued - A suitable academic programme may be designed and initiated based on Chembioinformatics D~~ _L~ -.. Prof P. Sreenivasa Kumar Dr. B. Manikiam --- Prof. Rajeev Bhargava Dr.~rathap Dr.fJd Dr. Sachin Chaturvedi ~ Shri Ajit Singh Llt R 4PI (TF Chairman -Member) Evaluation Report -CBDD ISC0203 Pg 15

16 ~~ Head, CSIR-URDIP (TF Chairman Member) Director, CSIR-NISCAIR (TF Chairman Member).. Director, CSIR-NISTADS (TF Chairman Member) ~4n, Dr. S. Srikanth Dr~~a (Chairman) Evaluation Report -CBDD ISC0203 Pg 16