Details of Drug-Drug Interaction
| Drug General Information (ID: DDIZ6ONATE) | |||||||||
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| Drug Name | Sorafenib | Drug Info | Belinostat | Drug Info | |||||
| Drug Type | Small molecule | Small molecule | |||||||
| Therapeutic Class | Antineoplastics | Antineoplastics | |||||||
| Structure | |||||||||
| Mechanism of Sorafenib-Belinostat Interaction (Severity Level: Moderate) | |||||||||
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| UGT inhibition Click to Show/Hide Mechanism Graph | |||||||||
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| Drug Name | Sorafenib | Belinostat | |||||||
| Mechanism | UGT1A1 inhibitor | UGT1A1 substrate | |||||||
| Key Mechanism Factor 1 | |||||||||
| Factor Name | UDP-glucuronosyltransferase 1A1 |
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Structure
Sequence
MAVESQGGRPLVLGLLLCVLGPVVSHAGKILLIPVDGSHWLSMLGAIQQLQQRGHEIVVLAPDASLYIRDGAFYTLKTYPVPFQREDVKESFVSLGHNVFENDSFLQRVIKTYKKIKKDSAMLLSGCSHLLHNKELMASLAESSFDVMLTDPFLPCSPIVAQYLSLPTVFFLHALPCSLEFEATQCPNPFSYVPRPLSSHSDHMTFLQRVKNMLIAFSQNFLCDVVYSPYATLASEFLQREVTVQDLLSSASVWLFRSDFVKDYPRPIMPNMVFVGGINCLHQNPLSQEFEAYINASGEHGIVVFSLGSMVSEIPEKKAMAIADALGKIPQTVLWRYTGTRPSNLANNTILVKWLPQNDLLGHPMTRAFITHAGSHGVYESICNGVPMVMMPLFGDQMDNAKRMETKGAGVTLNVLEMTSEDLENALKAVINDKSYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAHDLTWYQYHSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH
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| Gene Name | UGT1A1 | ||||||||
| Uniprot ID | UD11_HUMAN | ||||||||
| KEGG Pathway | hsa:54658 | ||||||||
| Protein Family | UDP-glycosyltransferase family | ||||||||
| Protein Function |
[Isoform 1]: UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:15472229, PubMed:18004206, PubMed:18004212, PubMed:18719240, PubMed:19830808, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004206, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol, estrone and estriol (PubMed:15472229, PubMed:18719240, PubMed:23288867). Involved in the glucuronidation of bilirubin, a degradation product occurring in the normal catabolic pathway that breaks down heme in vertebrates (PubMed:17187418, PubMed:18004206, PubMed:19830808). Also catalyzes the glucuronidation the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan (PubMed:12181437, PubMed:18004212, PubMed:20610558).
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| Mechanism Description |
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| Recommended Action | |||||||||
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| Management | Concomitant use of belinostat with potent UGT1A1 inhibitors such as atazanavir should generally be avoided. Caution is advised when used with other agents that may also inhibit UGT1A1 such as nilotinib, pazopanib, regorafenib and sorafenib. Patients should be monitored closely for potentially increased adverse effects such as nausea, vomiting, diarrhea, thrombocytopenia, leukopenia (neutropenia and lymphopenia), anemia, infection, and hepatotoxicity. | ||||||||
| References | |||||||||||||||||||
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| 1 | Product Information. Beleodaq (belinostat). Spectrum Pharmaceuticals Inc, Irvine, CA. | ||||||||||||||||||