Identification

Summary

Telotristat ethyl is a tryptophan hydroxylase inhibitor that is used to treat carcinoid syndrome diarrhea.

Brand Names
Xermelo
Generic Name
Telotristat ethyl
DrugBank Accession Number
DB12095
Background

Telotristat ethyl is a prodrug of telotristat that was approved by the FDA in March 2017 as Xermelo.8 It was previously referred to as telotristat etiprate, the hippurate salt form; however, the FDA recommends the use of the name of the neutral form rather than that of the salt.4,5 Currently, telotristat ethyl is used to treat carcinoid syndrome diarrhea from neuroendocrine tumors that are inadequately controlled by short-acting somatostatin analog (SSA) treatment.8

Neuroendocrine cells are cells that secrete regulatory peptides and biogenic amines in response to chemical, neural, or other types of stimuli.6 Neuroendocrine tumors (NET) arising from these cells can therefore secrete chemical mediators into the bloodstream to cause side effects in distant sites, a phenomenon called carcinoid syndrome.6 The most common peptides and amines secreted by NET are histamines, tachykinins, kallikrein, and serotonin.12 Overexposure to serotonin can cause severe diarrhea, one of the main clinical symptoms of carcinoid syndrome.4 Serotonin is metabolized in the urinary metabolite 5-hydroxy indole acetic acid (u5-HIAA), and high levels of u5-HIAA is associated with poor survival outcome in patients with NET.4 The first line treatment of carcinoid syndrome diarrhea is SSA, but symptoms still reoccur over the course of the disease.4

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 574.99
Monoisotopic: 574.1707009
Chemical Formula
C27H26ClF3N6O3
Synonyms
  • Telotristat ethyl
External IDs
  • LX 1032
  • LX 1606
  • LX-1032
  • LX-1606
  • LX1032
  • LX1606

Pharmacology

Indication

Xermelo is indicated for the treatment of carcinoid syndrome diarrhea in combination with somatostatin analog (SSA) therapy in adults inadequately controlled by SSA therapy.8

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Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

In normal mice, telotristat etiprate (administered once daily for 4 days at doses of 15–300 mg/kg/day) was found to reduce serotonin levels throughout the gastrointestinal tract.1,2 These reductions occurred in a dose dependent fashion with maximal effects observed with doses of telotristat etiprate ≥150 mg/kg. No significant change in brain serotonin or 5-hydroxyindoleacetic acid (5-HIAA, a serotonin metabolite) was observed.1,2 Similar findings were seen in Sprague-Dawley rats. Gastrointestinal motility studies were conducted in rats using the charcoal meal test.1,2 There was a significant dose-related delay in both gastrointestinal transit and gastric emptying, associated with a reduction in blood serotonin levels and proximal colon serotonin.1,2

A quantitative whole-body autoradiography study was conducted to assess the absorption, distribution and excretion of radioactivity in rats following a single oral dose of telotristat etiprate labeled with carbon 14.1,2 Rats were administered either 30 mg/kg or 100 mg/kg of the compound. The distribution of radioactivity was limited to tissues of the hepatic and renal system and the contents of the GI tract. There was no measurable radioactivity in the brain at any dose tested.1,2

Mechanism of action

Telotristat, the active metabolite of telotristat ethyl, is an inhibitor of tryptophan hydroxylase, which mediates the rate-limiting step in serotonin biosynthesis. The in vitro inhibitory potency of telotristat towards tryptophan hydroxylase is 29 times higher than that of telotristat ethyl. Serotonin plays a role in mediating secretion, motility, inflammation, and sensation of the gastrointestinal tract, and is over-produced in patients with carcinoid syndrome. Through inhibition of tryptophan hydroxylase, telotristat and telotristat ethyl reduce the production of peripheral serotonin, and the frequency of carcinoid syndrome diarrhea.8

TargetActionsOrganism
ATryptophan 5-hydroxylase 2
antagonist
Humans
ATryptophan 5-hydroxylase 1
antagonist
Humans
Absorption

After a single oral dose of telotristat ethyl to healthy subjects, telotristat ethyl was absorbed and metabolized to its active metabolite, telotristat. Peak plasma concentrations of telotristat ethyl were achieved within 0.5 to 2 hours, and those of telotristat within 1 to 3 hours. Plasma concentrations thereafter declined in a biphasic manner. Following administration of a single 500 mg dose of telotristat ethyl (twice the recommended dosage) under fasted conditions in healthy subjects, the mean Cmax and AUC0-inf were 4.4 ng/mL and 6.23 ng•hr/mL, respectively for telotristat ethyl. The mean Cmax and AUC0-inf were 610 ng/mL and 2320 ng•hr/mL, respectively for telotristat. Peak plasma concentrations and AUC of telotristat ethyl and telotristat appeared to be dose proportional following administration of a single dose of telotristat ethyl in the range of 100 mg (0.4 times the lowest recommended dose to 1000 mg [4 times the highest recommended dose]) under fasted conditions.8

Following multiple-dose administration of telotristat ethyl 500 mg three times daily, there was negligible accumulation at steady state for both telotristat ethyl and telotristat.8

In patients with metastatic neuroendocrine tumors and carcinoid syndrome diarrhea treated with SSA therapy, the median Tmax for telotristat ethyl and telotristat was approximately 1 and 2 hours, respectively. Following administration of 500 mg telotristat ethyl three times daily, with meals in patients, the mean Cmax and AUC0-6hr were approximately 7 ng/mL and 22 ng•hr/mL, respectively, for telotristat ethyl. The mean Cmax and AUC0-6hr were approximately 900 ng/mL and 3000 ng•hr/mL, respectively for telotristat. The pharmacokinetic parameters for both telotristat ethyl and telotristat were highly variable with about 55% coefficient of variation.8

Volume of distribution

The estimated apparent total volume of distribution for the active metabolite from the Population PK model of 428.1 L in a typical healthy fasted subject and 348.7 L in patients with carcinoid syndrome.11

Protein binding

Both telotristat ethyl and telotristat are greater than 99% bound to human plasma proteins.8

Metabolism

After oral administration, telotristat ethyl undergoes hydrolysis via carboxylesterases to telotristat, its active metabolite. Telotristat is further metabolized.8 Among the metabolites of telotristat, the systemic exposure to an acid metabolite of oxidative deaminated decarboxylated telotristat was about 35% of that of telotristat.8 In vitro data suggest that telotristat ethyl and telotristat are not substrates for CYP enzymes.8

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Route of elimination

Following a single 500 mg oral dose of 14C-telotristat ethyl, 93.2% of the dose was recovered over 240 hours: 92.8% was recovered in the feces, with less than 0.4% being recovered in the urine.8

Half-life

Following a single 500 mg oral dose of telotristat ethyl in healthy subjects, the apparent half-life was approximately 0.6 hours for telotristat ethyl and 5 hours for telotristat.8

Clearance

The apparent total clearance at steady state (CL/Fss) following oral dosing with telotristat ethyl 500 mg three times daily for 14 days (twice the recommended dosage) in healthy subjects was 2.7 and 152 L/hr for telotristat ethyl and telotristat, respectively.8

Adverse Effects
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Toxicity

An embryo-fetal development study performed in rats with oral telotristat ethyl at doses up to 750 mg/kg/day (approximately 9 times the AUC [area under the plasma concentration-time curve] for the active metabolite at the RHD) during organogenesis produced no harm to embryo-fetal development.8

In pregnant rabbits treated orally with telotristat ethyl during organogenesis, an increased incidence of post-implantation loss at doses of 250 and 500 mg/kg/day (approximately 15 times the AUC for the active metabolite at RHD) and a decrease in fetal weight at 500 mg/kg/day (approximately 33 times the AUC for the active metabolite at the RHD) was observed. The adverse effects on embryo-fetal development were associated with maternal toxicity (impaired weight gain and/or mortality) at 250 and 500 mg/kg/day. No adverse effects on embryo-fetal development were observed at 125 mg/kg/day (approximately 5 times the AUC for the active metabolite at the RHD).8

A pre-/postnatal development study was conducted in rats using oral administration of 100, 200, and 500 mg/kg/day telotristat ethyl during organogenesis through lactation. An increased incidence of pup mortality was observed during postnatal days 0 to 4 at the maternal dose of 500 mg/kg/day (approximately 5 times the AUC for the active metabolite at the RHD). No developmental abnormalities or effects on growth, learning, memory or reproductive performance were observed through the maturation of offspring at maternal doses of up to 500 mg/kg/day in surviving offspring.8

In a 26-week study in transgenic (Tg.rasH2) mice, telotristat ethyl was not tumorigenic at oral doses up to 300 mg/kg/day (approximately 12 to 19 times the AUC for the active metabolite at the RHD).8

In a 2-year carcinogenicity study in Sprague-Dawley rats, telotristat ethyl was not tumorigenic at oral doses up to 170 mg/kg/day (approximately 2 to 5 times the AUC for the active metabolite at the RHD).8

Telotristat ethyl was negative in the in vitro Ames test, the in vitro chromosomal aberration test using Chinese hamster ovary cells, and the in vivo rat micronucleus test.8

Telotristat ethyl at oral doses up to 500 mg/kg/day (approximately 5 times the AUC for the active metabolite at the RHD) was found to have no effect on the fertility and reproductive performance of male or female rats.8

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe serum concentration of 1,2-Benzodiazepine can be decreased when it is combined with Telotristat ethyl.
AbemaciclibThe serum concentration of Abemaciclib can be decreased when it is combined with Telotristat ethyl.
AbirateroneThe serum concentration of Abiraterone can be decreased when it is combined with Telotristat ethyl.
AcalabrutinibThe serum concentration of Acalabrutinib can be decreased when it is combined with Telotristat ethyl.
AcenocoumarolThe serum concentration of Acenocoumarol can be decreased when it is combined with Telotristat ethyl.
AcetaminophenThe serum concentration of Acetaminophen can be decreased when it is combined with Telotristat ethyl.
AlbendazoleThe serum concentration of Albendazole can be decreased when it is combined with Telotristat ethyl.
AlclometasoneThe serum concentration of Alclometasone can be decreased when it is combined with Telotristat ethyl.
AlfentanilThe serum concentration of Alfentanil can be decreased when it is combined with Telotristat ethyl.
AlfuzosinThe serum concentration of Alfuzosin can be decreased when it is combined with Telotristat ethyl.
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Food Interactions
  • Take with a high fat meal. High fat food increases the bioavailability of telotristat ethyl.
  • Take with food. Food increases the bioavailability of telotristat ethyl.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Telotristat etiprate3T25U84H4U1137608-69-5XSFPZBUIBYMVEA-CELUQASASA-N
Active Moieties
NameKindUNIICASInChI Key
Telotristatprodrug381V4FCV2Z1033805-28-5NCLGDOBQAWBXRA-PGRDOPGGSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
XermeloTablet250 mg/1OralTersera Therapeutics Llc2020-10-05Not applicableUS flag
XermeloTablet, film coated250 mgOralSerb Sas2020-12-16Not applicableEU flag
XermeloTablet250 mg/1OralLexicon Pharmaceuticals, Inc.2017-03-01Not applicableUS flag
XermeloTablet, film coated250 mgOralSerb Sas2020-12-16Not applicableEU flag
XermeloTablet250 mgOralIpsen Biopharmaceuticals Canada Inc2018-12-07Not applicableCanada flag

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phenylalanine and derivatives. These are compounds containing phenylalanine or a derivative thereof resulting from reaction of phenylalanine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Phenylalanine and derivatives
Alternative Parents
Alpha amino acid esters / Phenylpyrimidines / Phenylpyrazoles / Amphetamines and derivatives / Alkyl aryl ethers / Aminopyrimidines and derivatives / Aralkylamines / Chlorobenzenes / Fatty acid esters / Aryl chlorides
show 11 more
Substituents
4-phenylpyrimidine / Alkyl aryl ether / Alkyl fluoride / Alkyl halide / Alpha-amino acid ester / Amine / Aminopyrimidine / Amphetamine or derivatives / Aralkylamine / Aromatic heteromonocyclic compound
show 31 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
8G388563M7
CAS number
1033805-22-9
InChI Key
MDSQOJYHHZBZKA-GBXCKJPGSA-N
InChI
InChI=1S/C27H26ClF3N6O3/c1-3-39-25(38)20(32)12-16-4-6-17(7-5-16)21-14-23(35-26(33)34-21)40-24(27(29,30)31)19-9-8-18(28)13-22(19)37-11-10-15(2)36-37/h4-11,13-14,20,24H,3,12,32H2,1-2H3,(H2,33,34,35)/t20-,24+/m0/s1
IUPAC Name
ethyl (2S)-2-amino-3-(4-{2-amino-6-[(1R)-1-[4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl}phenyl)propanoate
SMILES
CCOC(=O)[C@@H](N)CC1=CC=C(C=C1)C1=NC(N)=NC(O[C@H](C2=CC=C(Cl)C=C2N2C=CC(C)=N2)C(F)(F)F)=C1

References

General References
  1. Lamarca A, Barriuso J, McNamara MG, Hubner RA, Valle JW: Telotristat ethyl: a new option for the management of carcinoid syndrome. Expert Opin Pharmacother. 2016 Dec;17(18):2487-2498. Epub 2016 Nov 16. [Article]
  2. Kulke MH, O'Dorisio T, Phan A, Bergsland E, Law L, Banks P, Freiman J, Frazier K, Jackson J, Yao JC, Kvols L, Lapuerta P, Zambrowicz B, Fleming D, Sands A: Telotristat etiprate, a novel serotonin synthesis inhibitor, in patients with carcinoid syndrome and diarrhea not adequately controlled by octreotide. Endocr Relat Cancer. 2014 Oct;21(5):705-14. doi: 10.1530/ERC-14-0173. Epub 2014 Jul 10. [Article]
  3. Tian DD, Leonowens C, Cox EJ, Gonzalez-Perez V, Frederick KS, Scarlett YV, Fisher MB, Paine MF: Indinavir Increases Midazolam N-Glucuronidation in Humans: Identification of an Alternate CYP3A Inhibitor Using an In Vitro to In Vivo Approach. Drug Metab Dispos. 2019 Jul;47(7):724-731. doi: 10.1124/dmd.119.087007. Epub 2019 Apr 26. [Article]
  4. Pavel M, Gross DJ, Benavent M, Perros P, Srirajaskanthan R, Warner RRP, Kulke MH, Anthony LB, Kunz PL, Horsch D, Weickert MO, Lapuerta P, Jiang W, Kassler-Taub K, Wason S, Fleming R, Fleming D, Garcia-Carbonero R: Telotristat ethyl in carcinoid syndrome: safety and efficacy in the TELECAST phase 3 trial. Endocr Relat Cancer. 2018 Mar;25(3):309-322. doi: 10.1530/ERC-17-0455. Epub 2018 Jan 12. [Article]
  5. Kulke MH, Horsch D, Caplin ME, Anthony LB, Bergsland E, Oberg K, Welin S, Warner RR, Lombard-Bohas C, Kunz PL, Grande E, Valle JW, Fleming D, Lapuerta P, Banks P, Jackson S, Zambrowicz B, Sands AT, Pavel M: Telotristat Ethyl, a Tryptophan Hydroxylase Inhibitor for the Treatment of Carcinoid Syndrome. J Clin Oncol. 2017 Jan;35(1):14-23. doi: 10.1200/JCO.2016.69.2780. Epub 2016 Oct 28. [Article]
  6. Dillon JS, Chandrasekharan C: Telotristat ethyl: a novel agent for the therapy of carcinoid syndrome diarrhea. Future Oncol. 2018 May;14(12):1155-1164. doi: 10.2217/fon-2017-0340. Epub 2018 Jan 19. [Article]
  7. FDA Review- Telotristat [Link]
  8. FDA Approved Drug Products: XERMELO® (telotristat ethyl) tablets, for oral use 2022 [Link]
  9. FDA Approved Drug Products: Xermelo (telotristat ethyl) tablets for oral use [Link]
  10. CLINICAL PHARMACOLOGY AND BIOPHARMACEUTICS REVIEW(S) [Link]
  11. Assessment Report: Xermelo (International non-proprietary name telotristat ethyl) [Link]
  12. Carcinoid Syndrome [Link]
PubChem Compound
25025298
PubChem Substance
347828399
ChemSpider
28189674
BindingDB
445704
RxNav
1872441
ChEMBL
CHEMBL2105695
ZINC
ZINC000043205655
Wikipedia
Telotristat_ethyl

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentCarcinoid Syndrome3
3RecruitingTreatmentLocally Advanced Neuroendocrine Neoplasm / Metastatic Neuroendocrine Neoplasm1
3WithdrawnTreatmentCarcinoid Heart Disease / Small Intestinal NET1
2CompletedTreatmentCarcinoid Syndrome2
2CompletedTreatmentUlcerative Colitis1
2RecruitingSupportive CareLocally Advanced Unresectable Pancreatic Adenocarcinoma / Pancreatic Adenocarcinoma Metastatic / Recurrent Pancreatic Adenocarcinoma / Stage III Pancreatic Cancer AJCC v8 / Stage IV Pancreatic Cancer AJCC v81
2RecruitingTreatmentCarcinoid Syndrome / Metastatic Nonfunctional Well Differentiated Neuroendocrine Neoplasm1
2RecruitingTreatmentNeuroendocrine Tumors1
2TerminatedTreatmentBiliary Tract Cancer (BTC)1
2WithdrawnSupportive CareCarcinoid Syndrome / Diarrhea / Neuroendocrine Tumors1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral250 mg
TabletOral250 mg/1
Tablet, film coatedOral250 MG
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US7553840No2009-06-302027-12-11US flag
US8193204No2012-06-052031-02-27US flag
US7968559No2011-06-282027-12-11US flag
US8653094No2014-02-182028-12-19US flag
US7709493No2010-05-042027-12-11US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility71 mg/mLL43342
Predicted Properties
PropertyValueSource
Water Solubility0.00294 mg/mLALOGPS
logP5.35ALOGPS
logP5.54Chemaxon
logS-5.3ALOGPS
pKa (Strongest Acidic)16.06Chemaxon
pKa (Strongest Basic)6.94Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count7Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area131.17 Å2Chemaxon
Rotatable Bond Count11Chemaxon
Refractivity144.98 m3·mol-1Chemaxon
Polarizability55.38 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Tryptophan 5-monooxygenase activity
Specific Function
Not Available
Gene Name
TPH2
Uniprot ID
Q8IWU9
Uniprot Name
Tryptophan 5-hydroxylase 2
Molecular Weight
56056.295 Da
References
  1. Kulke MH, O'Dorisio T, Phan A, Bergsland E, Law L, Banks P, Freiman J, Frazier K, Jackson J, Yao JC, Kvols L, Lapuerta P, Zambrowicz B, Fleming D, Sands A: Telotristat etiprate, a novel serotonin synthesis inhibitor, in patients with carcinoid syndrome and diarrhea not adequately controlled by octreotide. Endocr Relat Cancer. 2014 Oct;21(5):705-14. doi: 10.1530/ERC-14-0173. Epub 2014 Jul 10. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Tryptophan 5-monooxygenase activity
Specific Function
Not Available
Gene Name
TPH1
Uniprot ID
P17752
Uniprot Name
Tryptophan 5-hydroxylase 1
Molecular Weight
50984.725 Da
References
  1. Kulke MH, O'Dorisio T, Phan A, Bergsland E, Law L, Banks P, Freiman J, Frazier K, Jackson J, Yao JC, Kvols L, Lapuerta P, Zambrowicz B, Fleming D, Sands A: Telotristat etiprate, a novel serotonin synthesis inhibitor, in patients with carcinoid syndrome and diarrhea not adequately controlled by octreotide. Endocr Relat Cancer. 2014 Oct;21(5):705-14. doi: 10.1530/ERC-14-0173. Epub 2014 Jul 10. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Inducer
General Function
Vitamin d3 25-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 performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Flockhart Table of Drug Interactions [Link]
  2. Assessment Report: Xermelo (International non-proprietary name telotristat ethyl) [Link]
Kind
Protein
Organism
Humans
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
References
  1. FDA Approved Drug Products: XERMELO® (telotristat ethyl) tablets, for oral use 2022 [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Triglyceride lipase activity
Specific Function
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acy...
Gene Name
CES1
Uniprot ID
P23141
Uniprot Name
Liver carboxylesterase 1
Molecular Weight
62520.62 Da
References
  1. FDA Approved Drug Products: XERMELO® (telotristat ethyl) tablets, for oral use 2022 [Link]
  2. CLINICAL PHARMACOLOGY AND BIOPHARMACEUTICS REVIEW(S) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Methylumbelliferyl-acetate deacetylase activity
Specific Function
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Shows high catalytic efficiency for hydrolysis of cocaine, 4-methylumbelliferyl acetate, heroin and ...
Gene Name
CES2
Uniprot ID
O00748
Uniprot Name
Cocaine esterase
Molecular Weight
61806.41 Da
References
  1. CLINICAL PHARMACOLOGY AND BIOPHARMACEUTICS REVIEW(S) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inducer
General Function
Glucuronosyltransferase activity
Specific Function
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme is active on polyhydroxylated estrogens (such as...
Gene Name
UGT2B4
Uniprot ID
P06133
Uniprot Name
UDP-glucuronosyltransferase 2B4
Molecular Weight
60512.035 Da
References
  1. Tian DD, Leonowens C, Cox EJ, Gonzalez-Perez V, Frederick KS, Scarlett YV, Fisher MB, Paine MF: Indinavir Increases Midazolam N-Glucuronidation in Humans: Identification of an Alternate CYP3A Inhibitor Using an In Vitro to In Vivo Approach. Drug Metab Dispos. 2019 Jul;47(7):724-731. doi: 10.1124/dmd.119.087007. Epub 2019 Apr 26. [Article]
  2. FDA Approved Drug Products: XERMELO® (telotristat ethyl) tablets, for oral use 2022 [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inducer
General Function
Glucuronosyltransferase activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
Gene Name
UGT2B7
Uniprot ID
P16662
Uniprot Name
UDP-glucuronosyltransferase 2B7
Molecular Weight
60694.12 Da
References
  1. Tian DD, Leonowens C, Cox EJ, Gonzalez-Perez V, Frederick KS, Scarlett YV, Fisher MB, Paine MF: Indinavir Increases Midazolam N-Glucuronidation in Humans: Identification of an Alternate CYP3A Inhibitor Using an In Vitro to In Vivo Approach. Drug Metab Dispos. 2019 Jul;47(7):724-731. doi: 10.1124/dmd.119.087007. Epub 2019 Apr 26. [Article]
  2. FDA Approved Drug Products: XERMELO® (telotristat ethyl) tablets, for oral use 2022 [Link]
Kind
Protein
Organism
Humans
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
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Assessment Report: Xermelo (International non-proprietary name telotristat ethyl) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
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
References
  1. Assessment Report: Xermelo (International non-proprietary name telotristat ethyl) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
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
References
  1. Assessment Report: Xermelo (International non-proprietary name telotristat ethyl) [Link]
Kind
Protein
Organism
Humans
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
References
  1. Assessment Report: Xermelo (International non-proprietary name telotristat ethyl) [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
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
References
  1. FDA Approved Drug Products: XERMELO® (telotristat ethyl) tablets, for oral use 2022 [Link]

Transporters

Kind
Protein
Organism
Humans
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
References
  1. FDA Approved Drug Products: XERMELO® (telotristat ethyl) tablets, for oral use 2022 [Link]

Drug created at October 20, 2016 21:20 / Updated at December 01, 2022 11:27