Antiviral Off-Target Toxicity TestingPROVIDED BY REACHBIO
ReachBio works with clients during preclinical development of antiviral agents to help them predict and rank the potential of their drug candidates to induce myelosuppression (anemia, neutropenia, thrombocytopenia).
Our assay services predict or evaluate myelosuppression and hematotoxicity using CFC assays.
Our clients and others have been guided by the FDA to test their compounds using the CFC assay to determine if those drugs are hitting the bone marrow progenitors. To quote section C of the FDA guideline linked above, regarding Cytotoxicy and Therapeutic Indexes: “Because of the myelosuppressive effects of some antiviral products, we recommend assessing the potential effects of certain investigational products (e.g., nucleoside analogs) on the growth of human bone marrow progenitor cells in colony formation assays.”
ReachBio can perform these crucial assays which will meet those guidelines provided by the FDA. Our antiviral off-target toxicity testing platform will determine if an antiviral candidate expresses off-target toxicity before more resources are used to further research.
Despite successful therapeutic progress targeting a variety of viral infections and diseases (e.g. HIV, Hep B, Respiratory Viruses), antiviral drug development continues to be plagued with toxic side effects. Selective targeting of viruses is difficult to achieve due in part to the obligate intracellular ‘parasitic’ nature of viruses. Also, the classical nucleoside analog antiviral agents have typically had effects on the nucleic acid synthesis of normal cells, resulting in toxic side effects in tissues with rapidly dividing cells.
Whether directly targeting viral replication (e.g. inhibiting DNA, RNA or protein synthesis) [1,2,4], boosting the host immune system’s response via interferon therapy  or utilizing combination therapies (e.g. targeting chronic HCV via Ribavirin and peg-IFN alpha) , bone marrow toxicity is often associated with many of these drugs.
1. J.P. Sommadossi et. al.
Antimicrobial Agents and Chemotherapy. 1987; 31: 452-454.
Toxicity of 3'-azido-3'-deoxythymidine and 9-(1,3-dihydroxy-2-propoxymethyl)guanine for normal human hematopoietic progenitor cells in vitro.
2. R. Dornsife et. al.
Antimicrobial Agents and Chemotherapy. 1996 (Feb); 40(2): 514-519.
In vitro potency of inhibition by antiviral drugs of hematopoietic progenitor colony formation correlates with exposure at hemotoxic levels in human immunodeficiency virus-positive humans.
3. C.M. Drapeau et. al.
J Chemother. 2008 (Oct); 20(5): 648-651.
Bone marrow toxicity in HCV genotype 5a-infected patient after peg-IFN alpha-2a and ribavirin therapy.
4. A. Lam et. al.
Antimicrobial Agents and Chemotherapy. 2011 (Jun); 55(6): 2566-2575.
Inhibition of hepatitis C virus replicon RNA synthesis by PSI-352938, a cyclic phosphate prodrug of β-D-2'-deoxy-2'-α-fluoro-2'-β-C-methylguanosine.