DDInter1042 DDInter822
Leuprolide is a synthetic 9-residue peptide analogue of gonadotropin-releasing hormone (GnRH). Unlike the endogenous decapeptide GnRH, leuprolide contains a single D-amino acid (D-leucyl) residue, which helps to increase its circulating half-life from three to four minutes to approximately three hours. As a GnRH mimic, leuprolide is capable of binding to the GnRH receptor (GnRHR) and inducing downstream modulation of both gonadotropin hormone and sex steroid levels. Prolonged activation of GnRHR results in significant downregulation of sex steroid levels, which is primarily responsible for the clinical efficacy of leuprolide in diverse conditions, including advanced prostate cancer, endometriosis, and central precocious puberty.[A203126, A203132] Leuprolide was first approved in 1985 as a daily subcutaneous injection under the tradename
Glasdegib, also known as PF-04449913, is a small-molecule hedgehog signaling inhibitor selected under the group of benzimidazoles. In early research, benzimidazoles attracted large interest as they represented a class of inhibitors with low molecular weight, potent inhibitory activity, and lacking unstable functionality. The great lipophilicity of this group of compounds brought interest to further modification. This analysis concluded that the presence of p-cyano ureas presented good physicochemical and pharmacokinetic properties from which glasdegib was developed. Glasdegib was developed by Pfizer Inc and approved on November 21, 2018 by the FDA for the treatment of Acute Myeloid Leukemia (AML). Glasdegib targets cancerous cells by inhibiting the sonic hedgehog receptor smoothened (SMO), a transmembrane protein involved in the Hedgehog (Hh) signaling cascade. Aberrant of Hh signaling is one of the main pathophysiologies of AML, with observed overexpression or constitutive activation of SMO.[A258498,A258503] Although the efficacy of glasdegib monotherapy is limited, the landmark Phase 2 Bright AML 1003 trial showed a superior overall survival and complete response when glasdegib is combined with low dose cytarabine. Currently, the current gold standard of AML in older patients is still venetoclax with hypomethylation agents, new clinical combinations of glasdegib are being tested in hope of replacing venetoclax due to glasdegib's more favorable side effects profile.
Glasdegib {u} may cause a minor interaction that can limit clinical effects when taken with {v} Naloxegol
Glasdegib {u} may cause a minor interaction that can limit clinical effects when taken with {v} Darolutamide
Glasdegib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Abametapir
Glasdegib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Levosalbutamol
Glasdegib {u} may lead to a major life threatening interaction when taken with {v} Bedaquiline
Glasdegib {u} may lead to a major life threatening interaction when taken with {v} Ivosidenib
Glasdegib may cause a minor interaction that can limit clinical effects when taken with Naloxegol
Glasdegib may cause a minor interaction that can limit clinical effects when taken with Darolutamide
Glasdegib may cause a moderate interaction that could exacerbate diseases when taken with Abametapir
Glasdegib may cause a moderate interaction that could exacerbate diseases when taken with Levosalbutamol
Glasdegib may lead to a major life threatening interaction when taken with Bedaquiline
Glasdegib may lead to a major life threatening interaction when taken with Ivosidenib