Crisaborole is a topically administered, boron-containing, anti-inflammatory compound that inhibits the phosphodiesterase-4 (PDE4) activity and thereby suppresses the cytokine release of TNFalpha, IL-12, IL-23 and other cytokines. PDE4 is an an enzyme that converts the intracellular second messenger 3'5'-cyclic adenosine monophosphate (cAMP) into the active metabolite adenosine monophosphate (AMP). By inhibiting PDE4 and thus increasing levels of cAMP, crisaborole controls inflammation. The use of boron chemistry enabled synthesis of a low-molecular-weight compound (251 daltons), thereby facilitating effective penetration of crisaborole through human skin. Crisaborole is in clinical development for the topical treatment of psoriasis and being pursued for the topical treatment of atopic dermatitis. Preliminary studies in children and adults demonstrated favorable efficacy and safety profiles. Crisaborole may represent an anti-inflammatory option that safely minimizes the symptoms and severity of AD and that can be used for both acute and long-term management.

Tavaborole is a boron-based pharmaceutical agent indicated for the topical treatment of toenail onychomycosis, a fungal infection of the nail and nail bed due to Trichophyton rubrum or Trichophyton mentagrophytes infection. Tavaborole acts by inhibiting an aminoacyl-transfer ribonucleic acid (tRNA) synthetase (AARS) - Leucyl-tRNA synthetase. Leucyl-tRNA synthetase is an essential fungal enzyme required for protein synthesis and for the catalysis of ATP-dependent ligation of L-leucine to tRNA(Leu). Tavaborole’s low molecular weight (approximately half of most antifungals, such as terbinafine and efinaconazole) permits optimal nail plate penetration, superior to that of existing topical antifungal medications.

AN-2718 is a member of a new class of antifungals, benzoxaboroles, which inhibit fungal growth by blocking protein synthesis. AN-2718 is being developed for the topical treatment of tinea pedis including the hard to treat mocassin-type, which at present is only treatable with oral antifungals. AN-2718 inhibits an essential protein synthesis enzyme, leucyl-transfer RNA synthetase, or LeuRS. AN-2718 Inhibits LeuRS by the OBORT mechanism of trapping tRNALEU in the editing site of LeuRS. AN-2718 has good MIC90 activity against the dermatophytes, T. rubrum and T. mentagrophytes, which supports its use as a topical agent to treat tinea pedis. AN-2718 has been used in trials studying Tinea Pedis, but its development has been discontinued.