Identification

Name
Letermovir
Accession Number
DB12070
Type
Small Molecule
Groups
Approved
Description

Letermovir recieved approval from the FDA on November 8th, 2017 for use in prophylaxis of cytomegalovirus (CMV) infection in allogeneic hematopoietic stem cell transplant patients [6]. It represents the first entry into a new class of CMV anti-infectives, DNA terminase complex inhibitors [3]. Letermovir has recieved both priority and orphan drug status from the FDA. It is currently marketed under the brand name Prevymis [6].

Structure
Thumb
Synonyms
Not Available
External IDs
AIC 246 / AIC-246 / AIC246 / MK-8228
Unapproved/Other Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PrevymisTablet, film coated240 mg/1OralMerck Sharp & Dohme Limited2017-11-08Not applicableUs
PrevymisInjection, solution20 mg/mLIntravenousMerck Sharp & Dohme Limited2017-11-08Not applicableUs
PrevymisTablet, film coated480 mg/1OralMerck Sharp & Dohme Limited2017-11-08Not applicableUs
PrevymisInjection, solution20 mg/mLIntravenousMerck Sharp & Dohme Limited2017-11-08Not applicableUs
Categories
UNII
1H09Y5WO1F
CAS number
917389-32-3
Weight
Average: 572.561
Monoisotopic: 572.20466805
Chemical Formula
C29H28F4N4O4
InChI Key
FWYSMLBETOMXAG-QHCPKHFHSA-N
InChI
InChI=1S/C29H28F4N4O4/c1-40-20-6-3-5-19(16-20)35-11-13-36(14-12-35)28-34-27-21(7-4-8-22(27)30)23(17-26(38)39)37(28)24-15-18(29(31,32)33)9-10-25(24)41-2/h3-10,15-16,23H,11-14,17H2,1-2H3,(H,38,39)/t23-/m0/s1
IUPAC Name
2-[(4S)-8-fluoro-3-[2-methoxy-5-(trifluoromethyl)phenyl]-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3,4-dihydroquinazolin-4-yl]acetic acid
SMILES
COC1=CC=CC(=C1)N1CCN(CC1)C1=NC2=C(C=CC=C2F)[[email protected]](CC(O)=O)N1C1=CC(=CC=C1OC)C(F)(F)F

Pharmacology

Indication

For use in prophylaxis of cytomegalovirus (CMV) infection and disease in adult CMV-seropositive recipients of an allogeneic hematopoietic stem cell transplant (HSCT) [FDA Label].

Structured Indications
Pharmacodynamics

Letermovir inhibits the activity of the DNA terminase complex of CMV thereby preventing the cutting of viral DNA into mature length genomes for packaging into viral particles [FDA Label]. Letemovir inhibits the DNA terminase complex with an EC50 of 2.1nM.

Mechanism of action

CMV relies on a DNA terminase complex consisting of multiple subunits (pUL51, pUL56, and pUL89) for processing of viral DNA. Viral DNA is produced in a single repeating strand which is then cut by the DNA terminase complex into individual viral genomes which can then be packaged into mature viral particles [2]. Letemovir inhibits the activity of this complex to prevent production of mature viral genomes and the production of viable viral particles. The exact nature of Letemovir's binding to this complex is not currently known. Initially, the observation of resistance-causing mutations in pUL56 suggested this subunit was the location of Letemovir binding [3]. However, resistance mutations have now been observed in pUL51, pUL56, and pUL89 [4]. It is possible that changes in amino acid sequence in one subunit could result in conformational changes to interacting subunits affecting Letemovir binding or that Letemovir interacts with multiple subunits of the complex but evidence towards either of these distinctions has not yet been seen. pUL89 is known to contain the endonuclease activity of the complex but because all members of the complex are necessary for targeting as well as protection from proteosomal degradation, it is difficult to discern if Letemovir inhibits pUL89's activity directly [5].

TargetActionsOrganism
ATripartite terminase subunit 1
inhibitor
Human cytomegalovirus (strain Merlin)
ATripartite terminase subunit 2
inhibitor
Human cytomegalovirus (strain Merlin)
ATripartite terminase subunit 3
inhibitor
Human cytomegalovirus (strain Merlin)
Absorption

Letermovir has a bioavailability of 94% in healthy subjects when administered without cyclosporin, 35% in HSCT recipients when administered without cyclosporin, and 85% in HSCT recipients when administered with cyclosporin [FDA Label].

Letermovir's Tmax is 45 min to 2.25 h [FDA Label]. Time to steady state has been observed to be 9-10 days.

Taking Letermovir with food increases Cmax by an average of 129.82% (range of 104.35%-161.50%) [FDA Label]. No significant effect on AUC has been observed .

Volume of distribution

The mean steady state volume of distrubution is 45.5L [FDA Label]

Protein binding

Letermovir has been observed to be 99% bound to plasma proteins at concentrations of 0.2-50 mg/L in vitro [FDA Label].

Metabolism

Letermovir undergoes a minor degree of metabolism through UGT1A1/1A3 [FDA Label].

Route of elimination

Letemovir is taken up by the liver through OATP1B1/3 transporters. 93% is excreted in the feces with 70% as the parent drug [FDA Label]. <2% is excreted in the urine.

Half life

The mean terminal half-life was observed to be 12 hours following administration of Letemovir 480 mg IV once daily [FDA Label].

Clearance

The mean clearance is 11.25 L/h in healthy subjects [1]

Toxicity

There is no human data on the safety of Letemovir in pregnancy [FDA Label]. Embryo-fetal toxicity and malformations have been observed in rats at exposures 11 times the human exposure at the recommended human dose (RHD) of Letemovir. No such toxicity was noted in rats at 3 times human exposure at the RHD or in rabbits at values less than human exposure with the RHD. Total litter loss was observed in 21.7% of female rats at 2 times human exposure at RHD. This did not occur at values similar to human exposure at RHD.

No human data is available regarding lactation [FDA Label]. Letemovir has been observed in the milk of lactating rats and in the blood of their nursing pups.

No data is available concerning the effect of Letemovir on human fertility [FDA Label]. Testicular toxicity leading to reduced fertility has been observed in male rats.

No antidote exists for Letemovir overdosage [FDA Label]. The effectiveness of dialysis in clearing plasma of Letemovir is unknown.

Affected organisms
  • Human Cytomegalovirus
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of Letermovir can be increased when it is combined with Abiraterone.Approved
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Letermovir.Approved
AmiodaroneThe metabolism of Letermovir can be decreased when combined with Amiodarone.Approved, Investigational
AmodiaquineThe serum concentration of Amodiaquine can be increased when it is combined with Letermovir.Approved, Investigational
AmodiaquineThe serum concentration of Amodiaquine can be increased when it is combined with Letermovir.Approved, Investigational
ArtemetherThe metabolism of Letermovir can be decreased when combined with Artemether.Approved
AtomoxetineThe metabolism of Letermovir can be decreased when combined with Atomoxetine.Approved
BetaxololThe metabolism of Letermovir can be decreased when combined with Betaxolol.Approved
BosutinibThe serum concentration of Bosutinib can be increased when it is combined with Letermovir.Approved
Brentuximab vedotinThe serum concentration of Brentuximab vedotin can be increased when it is combined with Letermovir.Approved
BupropionThe metabolism of Letermovir can be decreased when combined with Bupropion.Approved
CelecoxibThe metabolism of Letermovir can be decreased when combined with Celecoxib.Approved, Investigational
ChloroquineThe metabolism of Letermovir can be decreased when combined with Chloroquine.Approved, Vet Approved
ChlorpromazineThe metabolism of Letermovir can be decreased when combined with Chlorpromazine.Approved, Vet Approved
CholecalciferolThe metabolism of Letermovir can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
Cholic AcidLetermovir may decrease the excretion rate of Cholic Acid which could result in a higher serum level.Approved
CimetidineThe metabolism of Letermovir can be decreased when combined with Cimetidine.Approved
CinacalcetThe metabolism of Letermovir can be decreased when combined with Cinacalcet.Approved
CitalopramThe metabolism of Letermovir can be decreased when combined with Citalopram.Approved
ClemastineThe metabolism of Letermovir can be decreased when combined with Clemastine.Approved
ClobazamThe metabolism of Letermovir can be decreased when combined with Clobazam.Approved, Illicit
ClomipramineThe metabolism of Letermovir can be decreased when combined with Clomipramine.Approved, Vet Approved
ClotrimazoleThe metabolism of Letermovir can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe metabolism of Letermovir can be decreased when combined with Clozapine.Approved
CobicistatThe serum concentration of Letermovir can be increased when it is combined with Cobicistat.Approved
CocaineThe metabolism of Letermovir can be decreased when combined with Cocaine.Approved, Illicit
ColchicineThe serum concentration of Colchicine can be increased when it is combined with Letermovir.Approved
Dabigatran etexilateThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Letermovir.Approved
DarifenacinThe metabolism of Letermovir can be decreased when combined with Darifenacin.Approved, Investigational
DarunavirThe serum concentration of Letermovir can be increased when it is combined with Darunavir.Approved
DelavirdineThe metabolism of Letermovir can be decreased when combined with Delavirdine.Approved
DesipramineThe metabolism of Letermovir can be decreased when combined with Desipramine.Approved
DiphenhydramineThe metabolism of Letermovir can be decreased when combined with Diphenhydramine.Approved
DosulepinThe metabolism of Letermovir can be decreased when combined with Dosulepin.Approved
DoxorubicinThe serum concentration of Doxorubicin can be increased when it is combined with Letermovir.Approved, Investigational
DronedaroneThe metabolism of Letermovir can be decreased when combined with Dronedarone.Approved
DuloxetineThe metabolism of Letermovir can be decreased when combined with Duloxetine.Approved
EdoxabanThe serum concentration of Edoxaban can be increased when it is combined with Letermovir.Approved
EliglustatThe metabolism of Letermovir can be decreased when combined with Eliglustat.Approved
EltrombopagThe serum concentration of Letermovir can be increased when it is combined with Eltrombopag.Approved
EverolimusThe serum concentration of Everolimus can be increased when it is combined with Letermovir.Approved
FluoxetineThe metabolism of Letermovir can be decreased when combined with Fluoxetine.Approved, Vet Approved
FluvoxamineThe metabolism of Letermovir can be decreased when combined with Fluvoxamine.Approved, Investigational
HaloperidolThe metabolism of Letermovir can be decreased when combined with Haloperidol.Approved
IbrutinibThe serum concentration of Ibrutinib can be increased when it is combined with Letermovir.Approved
ImipramineThe metabolism of Letermovir can be decreased when combined with Imipramine.Approved
IndinavirThe metabolism of Letermovir can be decreased when combined with Indinavir.Approved
IsoniazidThe metabolism of Letermovir can be decreased when combined with Isoniazid.Approved
KetoconazoleThe metabolism of Letermovir can be decreased when combined with Ketoconazole.Approved, Investigational
LedipasvirThe serum concentration of Ledipasvir can be increased when it is combined with Letermovir.Approved
LopinavirThe metabolism of Letermovir can be decreased when combined with Lopinavir.Approved
LorcaserinThe metabolism of Letermovir can be decreased when combined with Lorcaserin.Approved
LumacaftorThe serum concentration of Letermovir can be decreased when it is combined with Lumacaftor.Approved
LumefantrineThe metabolism of Letermovir can be decreased when combined with Lumefantrine.Approved
ManidipineThe metabolism of Letermovir can be decreased when combined with Manidipine.Approved, Investigational
MethadoneThe metabolism of Letermovir can be decreased when combined with Methadone.Approved
MethotrimeprazineThe metabolism of Letermovir can be decreased when combined with Methotrimeprazine.Approved
MetoprololThe metabolism of Letermovir can be decreased when combined with Metoprolol.Approved, Investigational
MidostaurinThe metabolism of Letermovir can be decreased when combined with Midostaurin.Approved
MirabegronThe metabolism of Letermovir can be decreased when combined with Mirabegron.Approved
NaloxegolThe serum concentration of Naloxegol can be increased when it is combined with Letermovir.Approved
NevirapineThe metabolism of Letermovir can be decreased when combined with Nevirapine.Approved
NicardipineThe metabolism of Letermovir can be decreased when combined with Nicardipine.Approved
NilotinibThe metabolism of Letermovir can be decreased when combined with Nilotinib.Approved, Investigational
PanobinostatThe serum concentration of Letermovir can be increased when it is combined with Panobinostat.Approved, Investigational
ParoxetineThe metabolism of Letermovir can be decreased when combined with Paroxetine.Approved, Investigational
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Letermovir.Approved
Peginterferon alfa-2bThe serum concentration of Letermovir can be decreased when it is combined with Peginterferon alfa-2b.Approved
PromazineThe metabolism of Letermovir can be decreased when combined with Promazine.Approved, Vet Approved
PrucaloprideThe serum concentration of Prucalopride can be increased when it is combined with Letermovir.Approved
QuinidineThe metabolism of Letermovir can be decreased when combined with Quinidine.Approved
QuinineThe metabolism of Letermovir can be decreased when combined with Quinine.Approved
RanolazineThe serum concentration of Ranolazine can be increased when it is combined with Letermovir.Approved, Investigational
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Letermovir.Approved, Investigational
RilpivirineThe serum concentration of Rilpivirine can be increased when it is combined with Letermovir.Approved
RitonavirThe metabolism of Letermovir can be decreased when combined with Ritonavir.Approved, Investigational
RolapitantThe metabolism of Letermovir can be decreased when combined with Rolapitant.Approved
RopiniroleThe metabolism of Letermovir can be decreased when combined with Ropinirole.Approved, Investigational
RucaparibThe metabolism of Letermovir can be decreased when combined with Rucaparib.Approved, Investigational
SertralineThe metabolism of Letermovir can be decreased when combined with Sertraline.Approved
SilodosinThe serum concentration of Silodosin can be increased when it is combined with Letermovir.Approved
StiripentolThe metabolism of Letermovir can be decreased when combined with Stiripentol.Approved
TerbinafineThe metabolism of Letermovir can be decreased when combined with Terbinafine.Approved, Investigational, Vet Approved
TeriflunomideThe serum concentration of Letermovir can be increased when it is combined with Teriflunomide.Approved
ThioridazineThe metabolism of Letermovir can be decreased when combined with Thioridazine.Approved, Withdrawn
TiclopidineThe metabolism of Letermovir can be decreased when combined with Ticlopidine.Approved
TipranavirThe metabolism of Letermovir can be decreased when combined with Tipranavir.Approved, Investigational
TolvaptanThe serum concentration of Tolvaptan can be increased when it is combined with Letermovir.Approved
TranylcypromineThe metabolism of Letermovir can be decreased when combined with Tranylcypromine.Approved
VemurafenibThe serum concentration of Letermovir can be increased when it is combined with Vemurafenib.Approved
VenlafaxineThe metabolism of Letermovir can be decreased when combined with Venlafaxine.Approved
VincristineThe serum concentration of Vincristine can be increased when it is combined with Letermovir.Approved, Investigational
ZiprasidoneThe metabolism of Letermovir can be decreased when combined with Ziprasidone.Approved
Food Interactions
Not Available

References

Synthesis Reference

Humphrey GR, Dalby SM, Andreani T, Xiang B, Luzung MR, Song ZJ, Shevlin M, Christensen M, Belyk KM, Tschaen DM. 2016.Asymmetric Synthesis of Letermovir Using a Novel Phase-Transfer Catalyzed Aza-Michael Reaction. Org. Process Res. Dev. 20(6), 1097-1103. DOI: 10.1021/acs.oprd.6b00076

General References
  1. Kropeit D, Scheuenpflug J, Erb-Zohar K, Halabi A, Stobernack HP, Hulskotte EGJ, van Schanke A, Zimmermann H, Rubsamen-Schaeff H: Pharmacokinetics and safety of letermovir, a novel anti-human cytomegalovirus drug, in patients with renal impairment. Br J Clin Pharmacol. 2017 Sep;83(9):1944-1953. doi: 10.1111/bcp.13292. Epub 2017 May 5. [PubMed:28345163]
  2. Goldner T, Hewlett G, Ettischer N, Ruebsamen-Schaeff H, Zimmermann H, Lischka P: The novel anticytomegalovirus compound AIC246 (Letermovir) inhibits human cytomegalovirus replication through a specific antiviral mechanism that involves the viral terminase. J Virol. 2011 Oct;85(20):10884-93. doi: 10.1128/JVI.05265-11. Epub 2011 Jul 13. [PubMed:21752907]
  3. Melendez DP, Razonable RR: Letermovir and inhibitors of the terminase complex: a promising new class of investigational antiviral drugs against human cytomegalovirus. Infect Drug Resist. 2015 Aug 5;8:269-77. doi: 10.2147/IDR.S79131. eCollection 2015. [PubMed:26345608]
  4. Chou S: A third component of the human cytomegalovirus terminase complex is involved in letermovir resistance. Antiviral Res. 2017 Dec;148:1-4. doi: 10.1016/j.antiviral.2017.10.019. Epub 2017 Oct 28. [PubMed:29107686]
  5. Neuber S, Wagner K, Goldner T, Lischka P, Steinbrueck L, Messerle M, Borst EM: Mutual Interplay between the Human Cytomegalovirus Terminase Subunits pUL51, pUL56, and pUL89 Promotes Terminase Complex Formation. J Virol. 2017 May 26;91(12). pii: e02384-16. doi: 10.1128/JVI.02384-16. Print 2017 Jun 15. [PubMed:28356534]
  6. FDA Approved Drugs: Letermovir [Link]
External Links
ChemSpider
26352849
ChEMBL
CHEMBL1241951
FDA label
Download (1.86 MB)
MSDS
Download (22.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedPreventionCytomegalovirus1
3CompletedPreventionInfections, Cytomegalovirus / Prevention of CMV Infection or Disease1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solutionIntravenous20 mg/mL
Tablet, film coatedOral240 mg/1
Tablet, film coatedOral480 mg/1
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.01 mg/mLALOGPS
logP4.58ALOGPS
logP4.64ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)3.75ChemAxon
pKa (Strongest Basic)7.15ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area77.84 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity147.44 m3·mol-1ChemAxon
Polarizability55 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylpiperazines. These are compounds containing a phenylpiperazine skeleton, which consists of a piperazine bound to a phenyl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazinanes
Sub Class
Piperazines
Direct Parent
Phenylpiperazines
Alternative Parents
N-arylpiperazines / Quinazolinamines / Trifluoromethylbenzenes / Aminophenyl ethers / Methoxyanilines / Anisoles / Dialkylarylamines / Phenoxy compounds / Methoxybenzenes / Alkyl aryl ethers
show 12 more
Substituents
Phenylpiperazine / N-arylpiperazine / Quinazolinamine / Quinazoline / Trifluoromethylbenzene / Aminophenyl ether / Methoxyaniline / Anisole / Phenol ether / Phenoxy compound
show 33 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human cytomegalovirus (strain Merlin)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Component of the molecular motor that translocates viral genomic DNA in empty capsid during DNA packaging. Forms a tripartite terminase complex together with TRM2 and TRM3 in the host cytoplasm. Once the complex reaches the host nucleus, it interacts with the capsid portal vertex. This portal forms a ring in which genomic DNA is translocated into the capsid. TRM1 carries an endonuclease activity that plays an important role for the cleavage of concatemeric viral DNA into unit length genomes.
Specific Function
Atp binding
Gene Name
TRM1
Uniprot ID
F5HC79
Uniprot Name
Tripartite terminase subunit 1
Molecular Weight
95810.305 Da
Kind
Protein
Organism
Human cytomegalovirus (strain Merlin)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Component of the molecular motor that translocates viral genomic DNA in empty capsid during DNA packaging. Forms a tripartite terminase complex together with TRM1 and TRM3 in the host cytoplasm. Once the complex reaches the host nucleus, it interacts with the capsid portal vertex. This portal forms a ring in which genomic DNA is translocated into the capsid.
Specific Function
Not Available
Gene Name
TRM2
Uniprot ID
F5HGI9
Uniprot Name
Tripartite terminase subunit 2
Molecular Weight
16977.55 Da
Kind
Protein
Organism
Human cytomegalovirus (strain Merlin)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Component of the molecular motor that translocates viral genomic DNA in empty capsid during DNA packaging. Forms a tripartite terminase complex together with TRM1 and TRM2 in the host cytoplasm. Once the complex reaches the host nucleus, it interacts with the capsid portal vertex. This portal forms a ring in which genomic DNA is translocated into the capsid. TRM3 carries an RNase H-like nuclease activity that plays an important role for the cleavage of concatemeric viral DNA into unit length genomes.
Specific Function
Dna binding
Gene Name
TRM3
Uniprot ID
F5HCU8
Uniprot Name
Tripartite terminase subunit 3
Molecular Weight
77033.575 Da

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A3
Uniprot ID
P35503
Uniprot Name
UDP-glucuronosyltransferase 1-3
Molecular Weight
60337.835 Da
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
8. Cytochrome p450 3A subfamily
Kind
Protein group
Organism
Human
Pharmacological action
No
Actions
Inhibitor

Transporters

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da

Drug created on October 20, 2016 15:18 / Updated on December 01, 2017 16:27