OSDD TB Drug Discovery Portfolio

OSDD pipeline to define the current status formulate our progression patterns with an intention of focusing our resources onto advanced projects to accelerate delivery. As can be seen in the pipeline, the focus is on the earlier part of the discovery path and programs like LAMS and CDRI 830 have starting points that have huge potential to be taken further. The program will now focus on detailing the structure activity relationship (SAR), defining chemical structures of the compounds that are responsible for biological activity (MIC on M. tuberculosis). This is a challenging phase of the program as delineating the target of the thiophene series and building the SAR correlation between the enzyme inhibitors and biological activity in the LAMS program is necessary for processing these compounds. The portfolio highlights the different approaches like whole cell based and/or target based along with different lead generation approaches such as, random, focused, virtual, natural product screening, substrate analogues etc. towards generating novel starting points. OSDD would like to establish necessary support functions to progress projects in the pipeline. For example, chemistry outsourcing and in vivo evaluation. OSDD hopes to bring compounds at later stages of development into clinical trials, to help complete the experience to deliver new drugs for TB therapy.


Screening

Hit to Lead

Whole Cell Based

Target Based

 

  • Screening of 20,000 drug like compounds:  analysis and prioritize new scaffolds
  • Screening of 30,000 compounds, in replicating and non replicating Mtb
  • Directed Chemistry Synthesis at CSIR Labs: > 40 projects IICT/NCL/NIIST/NEIST/CLRI- screening in progress in parallel
  • OSDDChem: > 30 projects from various institutes and universities; screening in parallel against TB and malaria
  • Plant derived anti-Infective library of pure compounds for screening
  • Focussed Coumarin library
  • Identification of anti-mycobacterial molecules from Actinomycetes.
  • Rv1018c (glmU):  Development of inhibitors through structure based drug design
  • (Dap A)/(Dap B): Identification of new inhibitors 
  • Structure-activity relationship study of NAD Dependent LigA inhibitors
  • Disruption of Sigma Factors-RNA polymerase interaction to target Mtb
  • Investigation on bioactive molecules inhibiting betalactamases and methionine aminopeptidases of Mtb
  • Identification of inhibitors targeting Mur pathway
  •  The role of dos regulon proteins of M. tuberculosis in persistence
  •  Phage based therapy for TB
  • CDRI-SOO6-830: SAR analysis, initial PK, MOA studies
  • LAMS (CSIR-IGIB and Jubilant Chemsys): Identifying new chemotypes & single target vs. multi target
  • Optimization of hits from whole cell based screening  for TB  

OSDD TB Drug Development Portfolio

OSDD has currently entered into agreement with Global TB Alliance for developing PA-824 in India, which will be taken into clinical trial in a three arm study to be conducted at LRS Institute of Tuberculosis andRespiratory Diseases. OSDD is also in discussion with various national and international organizations for the development of some clinical and pre-clinical candidates which includes both new drugs and repurposing drugs for treatment of TB.




List of Drug Targets in M.tuberculosis being pursued by OSDD 

1.            Rv0129c (Antigen 85 C)

2.            Rv2753c (dap A)

3.            Rv2773c (dap B)

4.            Rv1018c (glmU)

5.            Rv0548c (men B)

6.            Rv055c (men C)

7.            Rv0014c (PknB)

8.            Rv1258C

9.            FAAD’s

10.         MbtA

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Anshu Bhardwaj,
Apr 3, 2014, 6:50 AM