Case Studies

This was a four FTE multi-year contract. Small Molecule Kinase program.

Project requirements:

• Optimize the leads based on screening results, synthesize novel analogs of the leads for weekly screening
• Provide all medicinal chemistry expertise to client in designing new analogs and libraries. Explore new synthetic routes.

Accomplishments:

• Successfully met all the milestones and deadlines
• Provided more than 2000 compounds and many novel scaffolds during the tenure of the program.
• CreaGen was a true extension of customers medicinal chemistry program.

Multi-year FTE based program that involved synthesizing, linkers, small molecules and ADC conjugates.

Project requirements:

• Design and synthesize novel linkers.
• Conjugate novel small molecules and drug candidates to linkers.
• Introduce reactive functionalities on the linker to conjugate to antibodies.
• Provide conjugation chemistry expertise to client.
• Synthesize libraries of small molecules and explore new synthetic routes.

Accomplishments:

• Provided several conjugates to client for screening.
• Developed several novel hydrophilic molecules to conjugate to antibodies to minimize aggregation.
• Multi year renewal of collaborations
• True extension of customer’s ADC program

This was a five-year FTE based Lead Optimization program for a small biotech companies based in Massachusetts:

Project requirements:

• Function as medicinal chemistry department for client
• Provide all medicinal chemistry expertise in designing and synthesizing new analogs
• Synthesize analogs for weekly screening
• Develop SAR and interpret weekly screening results with client and suggest new ideas

Accomplishments:

• Met all the milestones during the contract work
• Expanded collaboration to 8 FTEs: Client was subsequently acquired by European pharmaceuticals.

This was a four year FTE based Lead generation and Lead optimization contract.

Project requirements:
• Functioned as de facto medicinal chemistry department
• Provided Integrated drug discovery services to the start-up
• Provided all medicinal chemistry expertise starting with design discussion, literature searches, hit-to-lead evaluation, SAR studies, lead optimization, identification and selection of high-value preclinical candidates

Accomplishments:
• Provided a nanomolar compound and several backup compounds.Expanded to 6 FTEs
• Project grew as milestones have been delivered. Program was subsequently licensed to another organization.

Biotech company focused on anti-infectives. Multi-year FTE based collaborations that involved Scaffold and lead molecule synthesis

Project Requirements:
• Design and synthesize novel scaffolds and develop new and efficient routes for the synthesis
• Provide multi-gram quantities of final compounds for in vivo tox studies with aggressive timeline
• Perform process development for multi-step synthesis of scaffolds and lead molecules

Accomplishments:
• Five year collaborations: Provided 150 scaffolds and multiple libraries of 2000 compounds were delivered.
• Several multigram scale non GMP compounds were synthesized for in-vivo and tox studies

Macrocyclic compounds Lead generation and Lead Optimization

Project Requirements:

• Design and Synthesis of 300-member focused macrocyclic compound library
• Sample delivery: dry form in duplicate bar-coded vials
• Quantity: 10 to 50 mg with purity >95+%: ¹H NMR and LCMS for all products in FID format

Accomplishments:

• Synthesized and delivered large compound library in client specified format on time
• Expansion and extension of the project

Lead optimization and Conjugation chemistry:

Project Requirements:

• Design and Synthesis of modified Tenofovir nucleosides with suitable site for linker
• Synthesis of FIAC, FMAU, FIAU, FAC, FAU, and FHMAU analogues with linkers
• Provide synthetic strategies for SBIR proposals

Accomplishments:

• Synthesized more 50 nucleoside analogs
• Synthesized sugar modified nucleosides
• Performed stability and rate-of-cleavage studies
• Expansion and extension of the project