New Small Molecule Drugs for Thrombocytopenia: Chemical, Pharmacological, and Therapeutic Use Considerations

• Published in: International journal of molecular sciences Vol. 20; no. 12; p. 3013
• Main Authors: Clemons Bankston, Page, Al-Horani, Rami A.
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20.06.2019; MDPI
• Subjects: Animals; Autoimmune diseases; Blood; Blood platelets; Bone marrow; Cinnamates - chemistry; Cinnamates - pharmacology; Cinnamates - therapeutic use; Cytokines; Drug Development; Drugs; Humans; Immunoglobulins; Infections; Kinases; Ligands; Molecular weight; Oxazines - chemistry; Oxazines - pharmacology; Oxazines - therapeutic use; Peptides; Physiology; Proteins; Pyridines - chemistry; Pyridines - pharmacology; Pyridines - therapeutic use; Receptors, Thrombopoietin - agonists; Receptors, Thrombopoietin - metabolism; Review; Rheumatoid arthritis; Signal transduction; Small Molecule Libraries - chemistry; Small Molecule Libraries - pharmacology; Small Molecule Libraries - therapeutic use; Spleen; Stem cells; Syk Kinase - antagonists & inhibitors; Syk Kinase - metabolism; Thiazoles - chemistry; Thiazoles - pharmacology; Thiazoles - therapeutic use; Thiophenes - chemistry; Thiophenes - pharmacology; Thiophenes - therapeutic use; Thrombocytopenia - drug therapy; Thrombocytopenia - metabolism; Viral infections; avatrombopag; fostamatinib; lusutrombopag
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20123013

This review provides details about three small molecules that were recently approved by the FDA for the treatment of thrombocytopenia. The new treatments include lusutrombopag, avatrombopag, and fostamatinib. The first two drugs are orally active thrombopoietin receptor (TPO-R) agonists which are FDA-approved for the treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure. Fostamatinib is orally active prodrug that, after activation, becomes spleen tyrosine kinase (SYK) inhibitor. Fostamatinib is currently used to treat chronic and refractory immune thrombocytopenia in patients who have had insufficient response to previous treatment. Chemical structures, available dosage forms, recommended dosing, pharmacokinetics, results of toxicity studies in animals, most frequent adverse effects, significant outcomes of the corresponding clinical trials, and their use in specific patient populations are thoroughly described. Described also is a comparative summary of the different aspects of five currently available therapies targeting TPO-R or SYK for the treatment of thrombocytopenia.