Recipient Organization
KAINOMYX INC
3035 COUNTRY CLUB CT
PALO ALTO,CA 94304
Performing Department
(N/A)
Non Technical Summary
Coccidiosis is a disease caused by microscopic parasites that infect the intestines of animals, particularly poultry, leading to severe health problems and significant economic losses in the livestock farming industry. At Kainomyx, we aim to find new treatments to combat this disease effectively.We use a non-conventional scientific approach called "target-based drug discovery." Here's how it works:1. Identify the Target: First, we study the parasite causing coccidiosis to find a specific part of it (a target) that we can attack with a drug. This target is usually a protein or enzyme essential for the parasite's survival or reproduction.2. Screen for Small Molecules: Next, we search for small chemicals (potential therapeutics, non-antibiotics) that can interact with our target. We test thousands of these molecules to find ones that can effectively disable or kill the parasite without harming the host animal.3. Develop Therapeutics: Once we identify promising small molecules, we refine and develop them into safe and effective treatments that can protect animals from coccidiosis.Using this three-step methodology, supported by the USDA grant, we aim to provide new solutions to keep our livestock healthy, improve food safety, and reduce economic losses in livestock agriculture.
Animal Health Component
50%
Research Effort Categories
Basic
50%
Applied
50%
Developmental
0%
Goals / Objectives
Overall objectiveWe aim to develop promising molecules against cytoskeletal targets into lead compounds to treat coccidiosis in poultry. Our drugs have a novel mechanism of killing the Eimeria parasites by inhibiting apicomplexan cytoskeletal protein networks, consistent with being used as a treatment and prophylaxis. In pursuit of this goal, we will address the following technical questions: (i) What chemical structures can inhibit the Eimeria MyoA protein activity selectively and potently? (ii) Are these chemical moieties effective in killing the Eimeria parasites without causing host cell morbidity? (iii) If not, how can changes to the structures of these molecules be tuned to optimize cellular performance, maximize intestinal stability, and minimize in vivo toxicity and residual compound/metabolites within the meat? (iv) How will these properties get translated into challenged and unchallenged chickens? To answer these questions, we have four main objectives:Objective 1: To identify novel hit candidates against Eimeria MyoA protein (0-6 months)Objective 2: To identify novel hit candidates from the Eimeria MyoA protein studies (Obj 1) that show cellular inhibitory properties against Eimeria parasites (3-6 months)Objective 3: To identify different pharmacochemical properties to develop cellular hits into lead molecules (0-6 months)Objective 4: Conduct in vivo safety and efficacy studies with existing or new lead compounds in unchallenged and challenged chicken models (6-8 months)
Project Methods
General Methods: As a general work plan, our target compounds will be prepared according to an established, flexible, and convergent synthesis previously exemplified on a gram scale. As part of Kainomyx's ongoing therapeutic discovery projects, the synthesis of these compounds is covered by other monies. In designing our compounds, we are aiming for compounds that have a low molecular weight (<500 g/mol) for ease of manufacturing and delivery, a low cLogP (2-4) to aid in tissue permeation, and highly solubility (>50-100 μM) to enable administration through aqueous solutions such as the drinking water. Our chemistry team will oversee the process, and the resulting compounds will undergo early-tier assays at Kainomyx. The compounds that pass testing will go through the standard drug discovery assay process. First, the synthesized compounds will be tested for potency and selectivity in biochemical and cellular environments. Then, their absorption, distribution, metabolism, and excretion (ADME) properties will be assessed in vitro. If the compounds meet the in vitro criteria, they will then be tested in vivo on chickens to evaluate safety and efficacy.