DDInter596 DDInter1087
Doxorubicin is a cytotoxic anthracycline antibiotic isolated from cultures of Streptomyces peucetius var. caesius along side with daunorubicin, another cytotoxic agent, in 1970.[A1575,A257709,A257614] Although they both have aglyconic and sugar moieties, doxorubicin's side chain terminates with a primary alcohol group compared to the methyl group of daunorubicin. Although its detailed molecular mechanisms have yet to be understood, doxorubicin is generally thought to exert its effect through DNA intercalation, which eventually leads to DNA damage and the generation of reactive oxygen species. Thanks to its efficacy and broad effect, doxorubicin was approved by the FDA in 1974 to treat a variety of cancer, including but not limited to breast, lung, gastric, ovarian, thyroid, non-Hodgkin’s and Hodgkin’s lymphoma, multiple myel
Hutchinson-Gilford progeria syndrome (HGPS) is a rare autosomal dominant disorder estimated to affect approximately one in 20 million individuals resulting in adverse symptoms associated with premature ageing: skeletal dysplasia, joint contractures, atherosclerosis, myocardial fibrosis/dysfunction, scleroderma-like cutaneous effects, lipoatrophy, alopecia, and a severe failure to thrive; HGPS is uniformly fatal.[A224379, A224384, A224389, A224394, A224399] Mechanistically, HGPS is underpinned by a single heterozygous C-to-T mutation at position 1824 of the _LMNA_ gene, which results in the accumulation of an aberrant farnesylated form of lamin A called progerin in the inner nuclear membrane.[A224379, A224394] Lonafarnib is a farnesyl transferase (FTase) inhibitor (FTI), which reduces the farnesylation of numerous cellular proteins, including progerin; as progerin farnesylation is important for localization to the nuclear membrane, lonafarnib inhibits progerin accumulation and improves symptoms in HGPS patients.[A224379, A224414, A224419, L23414] Merck originally developed Lonafarnib and subsequently licensed it to Eiger Biopharmaceuticals Inc., which currently markets it under the trademark ZOKINVY™.[L23414, L23544] Lonafarnib was granted FDA approval on November 20, 2020, and is the first FDA-approved treatment for HGPS and other related progeroid laminopathies.[L23414, L23549]
Doxorubicin {u} (Compound) resembles {v} (Compound) Epirubicin
Epirubicin {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Lonafarnib
Doxorubicin {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Sibutramine
Sibutramine {u} may cause a minor interaction that can limit clinical effects when taken with {v} Lonafarnib
Doxorubicin {u} (Compound) resembles {v} (Compound) Epirubicin
Epirubicin {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Tamoxifen
Tamoxifen {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Lonafarnib
Doxorubicin {u} (Compound) downregulates {v} (Gene) TXNDC9
TXNDC9 {u} (Gene) is downregulated by {v} (Compound) Sibutramine
Sibutramine {u} may cause a minor interaction that can limit clinical effects when taken with {v} Lonafarnib
Doxorubicin {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Loratadine
Loratadine {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Lonafarnib
Doxorubicin {u} (Compound) resembles {v} (Compound) Epirubicin
Epirubicin {u} may cause a minor interaction that can limit clinical effects when taken with {v} Metronidazole
Metronidazole {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Lonafarnib
Doxorubicin {u} (Compound) downregulates {v} (Gene) TXNDC9
TXNDC9 {u} (Gene) is downregulated by {v} (Compound) Albendazole
Albendazole {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Lonafarnib
Doxorubicin {u} (Compound) resembles {v} (Compound) Epirubicin
Epirubicin {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Brentuximab vedotin
Brentuximab vedotin {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Lonafarnib
Doxorubicin {u} (Compound) downregulates {v} (Gene) MTHFD2
MTHFD2 {u} (Gene) is upregulated by {v} (Compound) Sunitinib
Sunitinib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Lonafarnib
Doxorubicin {u} (Compound) downregulates {v} (Gene) TXNDC9
TXNDC9 {u} (Gene) is downregulated by {v} (Compound) Vemurafenib
Vemurafenib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Lonafarnib
Doxorubicin (Compound) resembles Epirubicin (Compound) and Epirubicin may cause a moderate interaction that could exacerbate diseases when taken with Lonafarnib
Doxorubicin (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Sibutramine (Compound) and Sibutramine may cause a minor interaction that can limit clinical effects when taken with Lonafarnib
Doxorubicin (Compound) resembles Epirubicin (Compound) and Epirubicin may cause a moderate interaction that could exacerbate diseases when taken with Tamoxifen and Tamoxifen may cause a moderate interaction that could exacerbate diseases when taken with Lonafarnib
Doxorubicin (Compound) downregulates TXNDC9 (Gene) and TXNDC9 (Gene) is downregulated by Sibutramine (Compound) and Sibutramine may cause a minor interaction that can limit clinical effects when taken with Lonafarnib
Doxorubicin (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Loratadine (Compound) and Loratadine may cause a moderate interaction that could exacerbate diseases when taken with Lonafarnib
Doxorubicin (Compound) resembles Epirubicin (Compound) and Epirubicin may cause a minor interaction that can limit clinical effects when taken with Metronidazole and Metronidazole may cause a moderate interaction that could exacerbate diseases when taken with Lonafarnib
Doxorubicin (Compound) downregulates TXNDC9 (Gene) and TXNDC9 (Gene) is downregulated by Albendazole (Compound) and Albendazole may cause a moderate interaction that could exacerbate diseases when taken with Lonafarnib
Doxorubicin (Compound) resembles Epirubicin (Compound) and Epirubicin may cause a moderate interaction that could exacerbate diseases when taken with Brentuximab vedotin and Brentuximab vedotin may cause a moderate interaction that could exacerbate diseases when taken with Lonafarnib
Doxorubicin (Compound) downregulates MTHFD2 (Gene) and MTHFD2 (Gene) is upregulated by Sunitinib (Compound) and Sunitinib may cause a moderate interaction that could exacerbate diseases when taken with Lonafarnib
Doxorubicin (Compound) downregulates TXNDC9 (Gene) and TXNDC9 (Gene) is downregulated by Vemurafenib (Compound) and Vemurafenib may cause a moderate interaction that could exacerbate diseases when taken with Lonafarnib