Characteristics of inorganic and small-molecule organic compound drugs, as well as macromolecule protein and nucleic acid therapeutics
| Properties | Inorganic Compound Drugs | Small-Molecule Organic Compound Drugs | Protein Therapeutics | RNA Therapeutics |
|---|---|---|---|---|
| Chemistry | Typical mol. wt. < 200 Da; ionic | Typical mol. wt. < 500 Da; hydrophobic | Typical mol. wt. > 100 kDa; positive/negative/neutral | Typical mol. wt. > 7 kDa; negative charge |
| Dosing | Primarily oral; often daily | Primarily oral; often daily | Mainly intravenous and subcutaneous; weekly to monthly | Intravenous, subcutaneous, intrathecal, intravitreal (various); weekly to once every 3–6 mo |
| ADME/PK properties | Orally 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 urine | excreted mainly in bile and urine | limited excretion | limited excretion | |
| Molecular targets | Proteins | Mainly proteins | Proteins | Mainly RNAs, besides proteins and DNAs |
| Site of action and PD | Extra-/intracellular; | Extra-/intracellular; | Extracellular/membrane; | Primarily intracellular; |
| direct or indirect relationship to blood PK | Direct or indirect relationship to blood PK | direct or indirect models linked to blood PK | more relevant to tissue PK, whereas PD can be linked to blood PK | |
| Safety/toxicity | Risk of off-target effects | Risk of off-target effects | Risk of immunogenicity | Risk of immunogenicity |
ADME, absorption, metabolism, distribution, and excretion.