DDInter458 DDInter822
Cyclosporine is a calcineurin inhibitor known for its immunomodulatory properties that prevent organ transplant rejection and treat various inflammatory and autoimmune conditions. It is isolated from the fungus _Beauveria nivea_. Initially manufactured by Sandoz and approved for use by the FDA in 1983, cyclosporine is now available in various products by Novartis (previously known as Sandoz).[L11097,L3734,L11118]
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.
Cyclosporine {u} (Compound) binds {v} (Gene) CYP2C8
CYP2C8 {u} (Gene) is bound by {v} (Compound) Sulfamethoxazole
Sulfamethoxazole {u} may cause a minor interaction that can limit clinical effects when taken with {v} Glasdegib
Cyclosporine {u} (Compound) binds {v} (Gene) CYP2C8
CYP2C8 {u} (Gene) is bound by {v} (Compound) Morphine
Morphine {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Glasdegib
Cyclosporine {u} (Compound) upregulates {v} (Gene) SLC1A4
SLC1A4 {u} (Gene) is upregulated by {v} (Compound) Sulfamethoxazole
Sulfamethoxazole {u} may cause a minor interaction that can limit clinical effects when taken with {v} Glasdegib
Cyclosporine {u} (Compound) downregulates {v} (Gene) PCNA
PCNA {u} (Gene) is downregulated by {v} (Compound) Sulfamethoxazole
Sulfamethoxazole {u} may cause a minor interaction that can limit clinical effects when taken with {v} Glasdegib
Cyclosporine {u} (Compound) upregulates {v} (Gene) SLC1A4
SLC1A4 {u} (Gene) is upregulated by {v} (Compound) Sorafenib
Sorafenib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Glasdegib
Cyclosporine {u} (Compound) causes {v} (Side Effect) Purpura
Purpura {u} (Side Effect) is caused by {v} (Compound) Sulfamethoxazole
Sulfamethoxazole {u} may cause a minor interaction that can limit clinical effects when taken with {v} Glasdegib
Cyclosporine {u} (Compound) downregulates {v} (Gene) PCNA
PCNA {u} (Gene) is downregulated by {v} (Compound) Sorafenib
Sorafenib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Glasdegib
Cyclosporine {u} (Compound) causes {v} (Side Effect) Purpura
Purpura {u} (Side Effect) is caused by {v} (Compound) Lomefloxacin
Lomefloxacin {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Glasdegib
Cyclosporine {u} (Compound) upregulates {v} (Gene) SLC1A4
SLC1A4 {u} (Gene) is upregulated by {v} (Compound) Dabrafenib
Dabrafenib {u} may lead to a major life threatening interaction when taken with {v} Glasdegib
Cyclosporine {u} (Compound) causes {v} (Side Effect) Thrombocytopenic purpura
Thrombocytopenic purpura {u} (Side Effect) is caused by {v} (Compound) Pimozide
Pimozide {u} may lead to a major life threatening interaction when taken with {v} Glasdegib
Cyclosporine (Compound) binds CYP2C8 (Gene) and CYP2C8 (Gene) is bound by Sulfamethoxazole (Compound) and Sulfamethoxazole may cause a minor interaction that can limit clinical effects when taken with Glasdegib
Cyclosporine (Compound) binds CYP2C8 (Gene) and CYP2C8 (Gene) is bound by Morphine (Compound) and Morphine may cause a moderate interaction that could exacerbate diseases when taken with Glasdegib
Cyclosporine (Compound) upregulates SLC1A4 (Gene) and SLC1A4 (Gene) is upregulated by Sulfamethoxazole (Compound) and Sulfamethoxazole may cause a minor interaction that can limit clinical effects when taken with Glasdegib
Cyclosporine (Compound) downregulates PCNA (Gene) and PCNA (Gene) is downregulated by Sulfamethoxazole (Compound) and Sulfamethoxazole may cause a minor interaction that can limit clinical effects when taken with Glasdegib
Cyclosporine (Compound) upregulates SLC1A4 (Gene) and SLC1A4 (Gene) is upregulated by Sorafenib (Compound) and Sorafenib may cause a moderate interaction that could exacerbate diseases when taken with Glasdegib
Cyclosporine (Compound) causes Purpura (Side Effect) and Purpura (Side Effect) is caused by Sulfamethoxazole (Compound) and Sulfamethoxazole may cause a minor interaction that can limit clinical effects when taken with Glasdegib
Cyclosporine (Compound) downregulates PCNA (Gene) and PCNA (Gene) is downregulated by Sorafenib (Compound) and Sorafenib may cause a moderate interaction that could exacerbate diseases when taken with Glasdegib
Cyclosporine (Compound) causes Purpura (Side Effect) and Purpura (Side Effect) is caused by Lomefloxacin (Compound) and Lomefloxacin may cause a moderate interaction that could exacerbate diseases when taken with Glasdegib
Cyclosporine (Compound) upregulates SLC1A4 (Gene) and SLC1A4 (Gene) is upregulated by Dabrafenib (Compound) and Dabrafenib may lead to a major life threatening interaction when taken with Glasdegib
Cyclosporine (Compound) causes Thrombocytopenic purpura (Side Effect) and Thrombocytopenic purpura (Side Effect) is caused by Pimozide (Compound) and Pimozide may lead to a major life threatening interaction when taken with Glasdegib