The US Department of Health and Human Services, National Institutes of Health has a continuing requirement for the Chemistry Center for Combating Antibiotic-Resistant Bacteria (CC4CARB).

The National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), of the Department of Health and Human Services (DHHS) supports research related to the basic understanding of microbiology and immunology leading to the development of vaccines, therapeutics, and medical diagnostics for the prevention, treatment, and diagnosis of infectious and immune-mediated diseases.

The Centers for Disease Control and Prevention (CDC) has developed a list of organisms considered Antimicrobial Resistance (AR) threats. Many of the organisms are multidrug-resistant Gram-negative bacteria.

The NIAID, Division of Microbiology and Infectious Diseases (DMID) has identified a significant lack of suitable chemical libraries accessible for screening as a major scientific bottleneck for the discovery and development of novel antimicrobial drugs due to multidrug-resistant (MDR) Gram-negative bacteria. There is a scarcity of novel chemical classes or natural compounds with properties appropriate for Gram-negative cell penetration and efflux avoidance.

The NIAID, Division of Microbiology and Infectious Diseases (DMID) has a requirement to support a Chemistry Center for Combating Antibiotic-Resistant Bacteria (CC4CARB) for supporting efforts to design, synthesize and deliver novel compound libraries to the scientific community for use in antibacterial drug discovery programs, particularly those targeting Gram-negative bacteria. The center will fit within the broader aims as stated in the National Action Plan for Combating Antibiotic Resistant Bacteria by synthesizing and delivering new compounds for antibacterial drug discovery, as well as chemical probes for establishing a better understanding of structure-activity relationships (SAR) for optimal activity against Gram-negative bacterial pathogens. Critical to the successful center will be strong capability for high-quality and timely synthesis of a diverse range of novel chemotypes, supported by well-organized process for review and approval of design proposals from external scientists and a seamless mechanism for managing the storage and distribution of the resulting compound libraries to the scientific community.

• The purpose of this contract is to continue the Chemistry Center for Combating Antibiotic-Resistant Bacteria (CC4CARB) responsible for coordinating and conducting the design, synthesis, in vitro testing, and distribution of chemical libraries of discrete natural products and small-molecules with diverse physicochemical properties, specifically designed to target Gram-negative bacterial pathogens and other antibiotic-resistant bacteria identified as Antimicrobial Resistance threats
• The CC4CARB will consist of requirements in four (4) key areas: 1)  Library Design, 2) Compound Synthesis, 3) Compound Testing, and 4) Compound Management, and includes Project Management of all efforts across these requirements
• CC4CARB’s Library Design Requirement involves community outreach and engagement with the global antibacterial research community to solicit design ideas for new compound libraries and chemical series. The ideas are to be expanded, through collaboration between CC4CARB and the proposer, into libraries of novel compounds possessing attributes favorable for antibacterial activity, cell penetration, efflux avoidance, or other beneficial properties toward antibacterial activity. Ideas will be reviewed by a Scientific Advisory Board (SAB) and approved for synthesis by the COR
• CC4CARB’s Compound Synthesis Requirement involves synthesizing the libraries that are identified by the Library Design effort. This may include various methods of acquiring compounds including purchase and donation, in addition to traditional synthesis. The libraries resulting from the center’s Compound Synthesis effort will be housed in the center’s Compound Management unit. The Government anticipates producing 1,500 to 2,000 rationally designed and structurally diverse compounds per year over the 5-year chemical synthesis phase of the contract
• CC4CARB’s Compound Testing Requirement involves generating Minimum Inhibitory Concentration (MIC) and potentially other in vitro data on each compound included in the CC4CARB collection in an assay panel that is consistent across all compounds tested, allowing cross-comparison of all compounds in the collection. The Compound Testing effort should be coordinated with Library Design and Compound Synthesis to enable iterative design improvements in follow-on libraries
• CC4CARB’s Compound Management Requirement involves maintaining the synthesized libraries in appropriate storage conditions and managing the distribution of compounds to members of the external scientific community, including public disclosure of compound structures, associated data, synthetic routes, and handling specifications in a free, searchable database
• Critical to success of this effort will be assignment of a single Principal Investigator (PI), ideally skilled in synthetic chemistry and medicinal chemistry, who will be accountable for coordinating all contract activities, along with comprehensive project management support, and for communicating progress and recommending approval decisions to the NIAID Contracting Officer’s Representative (COR)