Pyrazolopyrimidine compounds, methods of use, and processes for making compounds with anti-Mer tyrosine kinase activity comprising Formula I, II, III, IV, or a pharmaceutically acceptable composition, salt, isotopic analog, or prodrug thereof, are provided. The pyrazolopyrimidine compounds described herein have Mer tyrosine kinase (MerTK) inhibitory activity and are useful as anti-infective agents, immunostimulatory and immunomodulatory agents, anti-cancer agents (including against MerTK −/− tumors and ITD and TKD mutant forms of Acute Myeloid Leukemia (AML)), and as adjunctive agents in combination with chemotherapeutic, radiation or other standard of care for neoplasms.