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

General Information of Drug (ID: DR5430)
Drug Name
Remdesivir
Prodrug Info Remdesivir is the prodrug of GS-441524
Synonyms L-Alanine, N-((S)-hydroxyphenoxyp; RWWYLEGWBNMMLJ-YSOARWBDSA-N; Remdesivir [USAN]; 1809249-37-3; 3QKI37EEHE; AKOS032946252; SB19838; SCHEMBL17712225; UNII-3QKI37EEHE
Indication Coronavirus Disease 2019 (COVID-19) [ICD11: 1D6Y] Phase 3 [1]
Middle East Respiratory Syndrome (MERS) [ICD11: ICD11: 1D64] Investigative [2]
Severe acute respiratory syndrome (SARS) [ICD11: ICD11: 1D65] Investigative [3]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 602.6 Topological Polar Surface Area 204
Heavy Atom Count 42 Rotatable Bond Count 14
Hydrogen Bond Donor Count 4 Hydrogen Bond Acceptor Count 13
Cross-matching ID
PubChem CID
121304016
ChEBI ID
CHEBI:145994
CAS Number
1809249-37-3
TTD Drug ID
D01ICI
Formula
C27H35N6O8P
Canonical SMILES
CCC(CC)COC(=O)[C@H](C)N[P@](=O)(OC[C@@H]1[C@H]([C@H]([C@](O1)(C#N)C2=CC=C3N2N=CN=C3N)O)O)OC4=CC=CC=C4
InChI
InChI=1S/C27H35N6O8P/c1-4-18(5-2)13-38-26(36)17(3)32-42(37,41-19-9-7-6-8-10-19)39-14-21-23(34)24(35)27(15-28,40-21)22-12-11-20-25(29)30-16-31-33(20)22/h6-12,16-18,21,23-24,34-35H,4-5,13-14H2,1-3H3,(H,32,37)(H2,29,30,31)/t17-,21+,23+,24+,27-,42-/m0/s1
InChIKey
RWWYLEGWBNMMLJ-YSOARWBDSA-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
GS-441524 DM005163
44468216
Unclear 1 [7]
Remdesivir Alanine Metabolite (Ala-Met; GS-704277) DM005160 N. A. Unclear 1 [6]
Remdesivir carboxylate DM005158 N. A. Hydrolysis - Ester hydrolysis 1 [8]
Remdesivir M1 DM005166 N. A. Unclear 1 [6]
Remdesivir cyclic anhydride DM005159 N. A. Other reaction - Cyclization 2 [8]
Remdesivir Nucleoside Monophosphate DM005161
162482735
Unclear 2 [6]
GS-441524 DM005163
44468216
Unclear 3 [9]
Remdesivir Alanine Metabolite (Ala-Met; GS-704277) DM005160 N. A. Hydrolysis - Hydrolysis 3 [8]
Remdesivir Nucleoside Triphosphate DM005162 N. A. Conjugation - Phosphorylation 3 [10]
Remdesivir Nucleoside Monophosphate DM005161
162482735
Oxidation - Deamination 4 [8]
Remdesivir-DP DM005164 N. A. Hydrolysis - Hydrolysis 4 [4]
Remdesivir-MP DM005165 N. A. Hydrolysis - Hydrolysis 4 [4]
GS-441524 DM005163
44468216
Unclear 5 [8]
Remdesivir Nucleoside Triphosphate DM005162 N. A. Conjugation - Phosphorylation 5 [8]
⏷ Show the Full List of 14  DM(s)
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR013209 Remdesivir Remdesivir carboxylate Hydrolysis - Ester hydrolysis Unclear [8]
MR013215 Remdesivir Remdesivir Alanine Metabolite (Ala-Met; GS-704277) Unclear CES1 ... [6]
MR013218 Remdesivir Remdesivir M1 Unclear CYP3A4 ... [6]
MR013220 Remdesivir GS-441524 Unclear Unclear [7]
MR014047 Remdesivir Alanine Metabolite (Ala-Met; GS-704277) Remdesivir Nucleoside Monophosphate Unclear HINT1 [6]
MR013210 Remdesivir carboxylate Remdesivir cyclic anhydride Other reaction - Cyclization Unclear [8]
MR013219 Remdesivir M1 Remdesivir Nucleoside Monophosphate Unclear CES1 ... [6]
MR013211 Remdesivir cyclic anhydride Remdesivir Alanine Metabolite (Ala-Met; GS-704277) Hydrolysis - Hydrolysis Unclear [8]
MR014046 Remdesivir Nucleoside Monophosphate GS-441524 Unclear Unclear [9]
MR014048 Remdesivir Nucleoside Monophosphate Remdesivir Nucleoside Triphosphate Conjugation - Phosphorylation Unclear [10]
MR013212 Remdesivir Alanine Metabolite (Ala-Met; GS-704277) Remdesivir Nucleoside Monophosphate Oxidation - Deamination Unclear [8]
MR013216 Remdesivir Nucleoside Triphosphate Remdesivir-DP Hydrolysis - Hydrolysis NUDT18 [4]
MR013217 Remdesivir Nucleoside Triphosphate Remdesivir-MP Hydrolysis - Hydrolysis NUDT18 [4]
MR013213 Remdesivir Nucleoside Monophosphate Remdesivir Nucleoside Triphosphate Conjugation - Phosphorylation Unclear [8]
MR013214 Remdesivir Nucleoside Monophosphate GS-441524 Unclear ES [8]
⏷ Show the Full List of 15 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
8-oxo-dGDP phosphatase NUDT18 (NUDT18) DMEN258 Homo sapiens
NUD18_HUMAN
3.6.1.58
[4]
Acetylcholinesterase (ACHE) DME0058 Homo sapiens
ACES_HUMAN
3.1.1.7
[5]
Adenosine 5'-monophosphoramidase (HINT1) DME0215 Homo sapiens
HINT1_HUMAN
3.2.1.45
[6]
Butyrylcholine esterase (BCHE) DME0069 Homo sapiens
CHLE_HUMAN
3.1.1.8
[5]
Carboxylesterase 1 (CES1) DME0054 Homo sapiens
EST1_HUMAN
3.1.1.1
[6]
Carboxylesterase 1 (CES1) DME0054 Homo sapiens
EST1_HUMAN
3.1.1.1
[5]
Catechol 1,2-dioxygenase (catA) DMEN385 . Not Available Not Available [5] , [6]
Cathepsin A (CTSA) DME0071 Homo sapiens
PPGB_HUMAN
3.4.16.5
[6]
Cytochrome P450 2C8 (CYP2C8) DME0018 Homo sapiens
CP2C8_HUMAN
1.14.14.1
[6]
Cytochrome P450 2D6 (CYP2D6) DME0009 Homo sapiens
CP2D6_HUMAN
1.14.14.1
[6]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[6]
pyrophosphatase (PPase) DMEN831 Homo sapiens Not Available Not Available [4]
⏷ Show the Full List of 12  DME(s)
References
1 ClinicalTrials.gov (NCT04315948) Trial of Treatments for COVID-19 in Hospitalized Adults
2 Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun. 2020 Jan 10;11(1):222.
3 Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun. 2020 Jan 10;11(1):222.
4 Nudix hydrolase 18 catalyzes the hydrolysis of active triphosphate metabolites of the antivirals remdesivir, ribavirin, and molnupiravir
5 Human carboxylesterase 1A plays a predominant role in the hydrolytic activation of remdesivir in humans
6 Viral target and metabolism-based rationale for combined use of recently authorized small molecule COVID-19 medicines: Molnupiravir, nirmatrelvir, and remdesivir
7 Removal of Remdesivir's Metabolite GS-441524 by Hemodialysis in a Double Lung Transplant Recipient with COVID-19
8 Remdesivir: A Review of Its Discovery and Development Leading to Emergency Use Authorization for Treatment of COVID-19
9 Population pharmacokinetic modeling of GS-441524, the active metabolite of remdesivir, in Japanese COVID-19 patients with renal dysfunction
10 Remdesivir: Review of Pharmacology, Pre-clinical Data, and Emerging Clinical Experience for COVID-19

If you find any error in data or bug in web service, please kindly report it to Dr. Yin and Dr. Li.