Characteristics of inorganic and small-molecule organic compound drugs, as well as macromolecule protein and nucleic acid therapeutics

PropertiesInorganic Compound DrugsSmall-Molecule Organic Compound DrugsProtein TherapeuticsRNA Therapeutics
ChemistryTypical mol. wt. < 200 Da; ionicTypical mol. wt. < 500 Da; hydrophobicTypical mol. wt. > 100 kDa; positive/negative/neutralTypical mol. wt. > 7 kDa; negative charge
DosingPrimarily oral; often dailyPrimarily oral; often dailyMainly intravenous and subcutaneous; weekly to monthlyIntravenous, subcutaneous, intrathecal, intravitreal (various); weekly to once every 3–6 mo
ADME/PK propertiesOrally bioavailable;Orally bioavailable;Not orally bioavailable;Not orally bioavailable;
distributed to all organs and tissues, cell permeable;distributed to all organs and tissues, cell permeable;distributed mainly in plasma or extracellular fluids, cell impermeable;Distributed extensively to kidney and liver, cell impermeable;
usually not metabolized;metabolized by phase I and II enzymes;catabolized extensively to peptides or amino acids;catabolized extensively by nucleases to (oligo)nucleotides;
excreted primarily in urineexcreted mainly in bile and urinelimited excretionlimited excretion
Molecular targetsProteinsMainly proteinsProteinsMainly RNAs, besides proteins and DNAs
Site of action and PDExtra-/intracellular;Extra-/intracellular;Extracellular/membrane;Primarily intracellular;
direct or indirect relationship to blood PKDirect or indirect relationship to blood PKdirect or indirect models linked to blood PKmore relevant to tissue PK, whereas PD can be linked to blood PK
Safety/toxicityRisk of off-target effectsRisk of off-target effectsRisk of immunogenicityRisk of immunogenicity
  • ADME, absorption, metabolism, distribution, and excretion.