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Crisaborole Topical Ointment, 2%: A Nonsteroidal, Topical, Anti-Inflammatory Phosphodiesterase 4 Inhibitor in Clinical Development for the Treatment of Atopic Dermatitis.
J Drugs Dermatol. 2016 Apr; 15(4):390-6.JD

Abstract

Crisaborole topical ointment, 2% (formerly known as AN2728) is a benzoxaborole, nonsteroidal, topical, anti-inflammatory phosphodiesterase 4 (PDE4) inhibitor investigational compound that recently completed phase 3 studies for the treatment of mild to moderate atopic dermatitis (AD). The unique configuration of boron within the crisaborole molecule enables selective targeting and inhibition of PDE4, 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. In vitro experiments showed that crisaborole inhibits cytokine production from peripheral blood mononuclear cells in a pattern similar to other PDE4 inhibitors and distinct from corticosteroids. Crisaborole also displayed topical anti-inflammatory activity in a skin inflammation model. Once crisaborole reaches systemic circulation after topical application, it is metabolized to inactive metabolites. This limits systemic exposure to crisaborole and systemic PDE4 inhibition. In phase 1 and 2 clinical studies, crisaborole ointment, 2% was generally well tolerated and improved AD disease severity scores, pruritus, and all other AD signs and symptoms. Two large, randomized, controlled, phase 3, pivotal clinical trials assessing the efficacy and safety of crisaborole topical ointment, 2% in children, adolescents, and adults with mild to moderate AD were recently completed with positive results.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

27050693

Citation

Jarnagin, Kurt, et al. "Crisaborole Topical Ointment, 2%: a Nonsteroidal, Topical, Anti-Inflammatory Phosphodiesterase 4 Inhibitor in Clinical Development for the Treatment of Atopic Dermatitis." Journal of Drugs in Dermatology : JDD, vol. 15, no. 4, 2016, pp. 390-6.
Jarnagin K, Chanda S, Coronado D, et al. Crisaborole Topical Ointment, 2%: A Nonsteroidal, Topical, Anti-Inflammatory Phosphodiesterase 4 Inhibitor in Clinical Development for the Treatment of Atopic Dermatitis. J Drugs Dermatol. 2016;15(4):390-6.
Jarnagin, K., Chanda, S., Coronado, D., Ciaravino, V., Zane, L. T., Guttman-Yassky, E., & Lebwohl, M. G. (2016). Crisaborole Topical Ointment, 2%: A Nonsteroidal, Topical, Anti-Inflammatory Phosphodiesterase 4 Inhibitor in Clinical Development for the Treatment of Atopic Dermatitis. Journal of Drugs in Dermatology : JDD, 15(4), 390-6.
Jarnagin K, et al. Crisaborole Topical Ointment, 2%: a Nonsteroidal, Topical, Anti-Inflammatory Phosphodiesterase 4 Inhibitor in Clinical Development for the Treatment of Atopic Dermatitis. J Drugs Dermatol. 2016;15(4):390-6. PubMed PMID: 27050693.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Crisaborole Topical Ointment, 2%: A Nonsteroidal, Topical, Anti-Inflammatory Phosphodiesterase 4 Inhibitor in Clinical Development for the Treatment of Atopic Dermatitis. AU - Jarnagin,Kurt, AU - Chanda,Sanjay, AU - Coronado,Dina, AU - Ciaravino,Vic, AU - Zane,Lee T, AU - Guttman-Yassky,Emma, AU - Lebwohl,Mark G, PY - 2016/4/7/entrez PY - 2016/4/7/pubmed PY - 2017/1/4/medline SP - 390 EP - 6 JF - Journal of drugs in dermatology : JDD JO - J Drugs Dermatol VL - 15 IS - 4 N2 - Crisaborole topical ointment, 2% (formerly known as AN2728) is a benzoxaborole, nonsteroidal, topical, anti-inflammatory phosphodiesterase 4 (PDE4) inhibitor investigational compound that recently completed phase 3 studies for the treatment of mild to moderate atopic dermatitis (AD). The unique configuration of boron within the crisaborole molecule enables selective targeting and inhibition of PDE4, 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. In vitro experiments showed that crisaborole inhibits cytokine production from peripheral blood mononuclear cells in a pattern similar to other PDE4 inhibitors and distinct from corticosteroids. Crisaborole also displayed topical anti-inflammatory activity in a skin inflammation model. Once crisaborole reaches systemic circulation after topical application, it is metabolized to inactive metabolites. This limits systemic exposure to crisaborole and systemic PDE4 inhibition. In phase 1 and 2 clinical studies, crisaborole ointment, 2% was generally well tolerated and improved AD disease severity scores, pruritus, and all other AD signs and symptoms. Two large, randomized, controlled, phase 3, pivotal clinical trials assessing the efficacy and safety of crisaborole topical ointment, 2% in children, adolescents, and adults with mild to moderate AD were recently completed with positive results. SN - 1545-9616 UR - https://www.unboundmedicine.com/medline/citation/27050693/Crisaborole_Topical_Ointment_2:_A_Nonsteroidal_Topical_Anti_Inflammatory_Phosphodiesterase_4_Inhibitor_in_Clinical_Development_for_the_Treatment_of_Atopic_Dermatitis_ DB - PRIME DP - Unbound Medicine ER -