Author: Yvonne R. Freund, Tsutomu Akama, Pamela Berry, Yong-Kang Zhang, Eric Easom, Robert T. Jacobs, Jacob J. Plattner, Michael Witty, Tim Rowan, Rosemary Peter
Year: 2016
About this Publication:
Animal African Trypanosomosis (AAT) is a potentially fatal parasitic wasting disease of livestock and wild animals in sub-Saharan Africa. It is caused primarily by the two parasites, Trypanosoma congolense and Trypanasoma vivax, which are spread by tsetse flies and other biting flies. AAT is AAT is responsible for 3 million cattle deaths annually in sub-Saharan Africa and costs African livestock farmers approximately US $1- 5 billion per year. There are few available drugs for effective treatment and prophylaxis and most have a narrow therapeutic index. Standard-of-care drugs such as diminazene, isometamidium and homidium are old, often ineffective and both drug resistance and safety are of concern.1,2 Screening of the Anacor Pharmaceuticals library of novel boron-containing compounds identified a series of amino acid ester amides of benzoxaborole 6-carboxylic acids as subnanomolar potency inhibitors of T. congolense and T. vivax in in vitro and ex vivo assays. A lead optimization effort resulted in AN11736 which demonstrated 100% cure (>60 days parasite-free) with a single IP dose of 10 mg/kg against both T. congolense (N=4/grp, 20 experiments) and T.vivax (N = 4, 12 experiments) in mouse models. 100% cure was alsoobserved IM in the target animal species, cattle (>100 days parasite-free, N = 3or 6/grp in 2 experiments). AN11736 showed no issues in Ames, in vitromicronucleus, hERG and receptor panel assays. A seven-day repeat dose oraltoxicity study in dogs showed a NOAEL of 200 mg/kg for female (AUC =19.1h*?g/mL) and 600 mg/kg for male (AUC=31.6 h*?g/mL) dogs. AN11736 is a novel chemical entity which is being advanced to clinical development as the first novel drug for treatment of AAT in 50 years.
Grant: Tryps2
Subject Areas: Research and Development
Diseases: Trypanosomosis
Keywords:
Trypanosomosis, african animal trypanosomosis, anacor, clinical candidate, t congolense, t vivax
Countries:
Angola, Armenia, Azerbaijan, Bahrain, Burundi, Cameroon, Central African Republic, Chad, Comoros, Congo, Democratic Republic Of, Congo, Republic Of, Cyprus, Djibouti, Equatorial Guinea, Eritrea, Ethiopia, Gabon, Georgia, Iraq, Israel, Jordan, Kenya, Kuwait, Lebanon, Madagascar, Malawi, Mauritius, Mayotte, Mozambique, Oman, Palestinian Territory, Occupied, Qatar, Reunion, Rwanda, Sao Tome And Principe, Saudi Arabia, Seychelles, Somalia, Syrian Arab Republic, Tanzania, United Republic Of, Turkey, Uganda, United Arab Emirates, Yemen, Zambia, Zimbabwe
