Details of the Drug Metabolized by Drug-Metabolizing Enzyme (DME)

General Information of Drug (ID: DR0754)
Drug Name
Fostamatinib
Synonyms
Fostamatinib; Fostamatinib (R788); Fostamatinib(R788); Fostamatinib/R788; R-788 Free acid; R-935788 Free acid; R7935788; SQ8A3S5101; Tavalisse; 901119-35-5; R 788; R-788; R788; UNII-SQ8A3S5101; [6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-3-oxo-pyrido[3,2-b][1,4]oxazin-4-yl]methyl dihydrogen phosphate; [6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-3-oxopyrido[3,2-b][1,4]oxazin-4-yl]methyl dihydrogen phosphate
Indication Thrombocytopenia [ICD11: 3B64] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 580.5 Topological Polar Surface Area 187
Heavy Atom Count 40 Rotatable Bond Count 10
Hydrogen Bond Donor Count 4 Hydrogen Bond Acceptor Count 15
Cross-matching ID
PubChem CID
11671467
PubChem SID
16775273 ; 23769915 ; 75389485 ; 96026027 ; 124360793 ; 125164706 ; 125299332 ; 126665637 ; 134338877 ; 135262180 ; 135693729 ; 136367938 ; 137245316 ; 141853032 ; 144115995 ; 152159558 ; 152344305 ; 160681714 ; 162038039 ; 164043535 ; 164160256 ; 170501470 ; 172087031 ; 172818901 ; 174006453 ; 174531355 ; 185997057 ; 188941735 ; 198973453 ; 206261469 ; 210274820 ; 210280453 ; 223366127 ; 223388366 ; 223684830 ; 227435155 ; 242060176 ; 246229128 ; 251971029 ; 252215442
CAS Number
901119-35-5
TTD Drug ID
D0V8HJ
Formula
C23H26FN6O9P
Canonical SMILES
CC1(C(=O)N(C2=C(O1)C=CC(=N2)NC3=NC(=NC=C3F)NC4=CC(=C(C(=C4)OC)OC)OC)COP(=O)(O)O)C
InChI
1S/C23H26FN6O9P/c1-23(2)21(31)30(11-38-40(32,33)34)20-14(39-23)6-7-17(28-20)27-19-13(24)10-25-22(29-19)26-12-8-15(35-3)18(37-5)16(9-12)36-4/h6-10H,11H2,1-5H3,(H2,32,33,34)(H2,25,26,27,28,29)
InChIKey
GKDRMWXFWHEQQT-UHFFFAOYSA-N
The Metabolic Roadmap of This Drug
The Full List of Drug Metabolites (DM) of This Drug
DM Name DM ID PubChem ID Reaction DM Level REF
R406 DM002073
11213558
Unclear 1 [3]
R406 N-glucuronide metabolite DM002078 N. A. Conjugation - N-Glucuronidation 2 [4]
R529 DM002074
146675097
Unclear 2 [4]
3,5 benzene diol metabolite of R406 DM002075
146675106
Oxidation - Oxidation 3 [5]
R529 O-glucuronide metabolite DM002077 N. A. Conjugation - O-Glucuronidation 3 [4]
R529 Sulfate-conjugate metabolite DM002076 N. A. Conjugation - Sulfation 3 [4]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR001092 Fostamatinib R406 Unclear ALPL [3]
MR001087 R406 R529 Unclear CYP3A4 [4]
MR001088 R406 R406 N-glucuronide metabolite Conjugation - N-Glucuronidation UGT1A9 [4]
MR001089 R529 3,5 benzene diol metabolite of R406 Oxidation - Oxidation Unclear [5]
MR001090 R529 R529 Sulfate-conjugate metabolite Conjugation - Sulfation Unclear [4]
MR001091 R529 R529 O-glucuronide metabolite Conjugation - O-Glucuronidation Unclear [4]
⏷ Show the Full List of 6 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[2]
References
1 Fostamatinib was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Effects of CYP3A4 inhibitors ketoconazole and verapamil and the CYP3A4 inducer rifampicin on the pharmacokinetic parameters of fostamatinib: results from In vitro and phase I clinical studies. Drugs R D. 2016 Mar;16(1):81-92.
3 Metabolism of fostamatinib, the oral methylene phosphate prodrug of the spleen tyrosine kinase inhibitor R406 in humans: contribution of hepatic and gut bacterial processes to the overall biotransformation Drug Metab Dispos. 2010 Jul;38(7):1166-76. doi: 10.1124/dmd.110.032151.
4 DrugBank(Pharmacology-Metabolism)Fostamatinib
5 Clinical Pharmacokinetics and Pharmacodynamics of Fostamatinib and Its Active Moiety R406 Clin Pharmacokinet. 2022 Jul;61(7):955-972. doi: 10.1007/s40262-022-01135-0.

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