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Identification
- Summary
Trofinetide is a drug used to treat Rett syndrome in children and adults.
- Brand Names
- Daybue
- Generic Name
- Trofinetide
- DrugBank Accession Number
- DB06045
- Background
Trofinetide is a novel synthetic analog of glypromate, also known as glycine–proline–glutamate (GPE), a naturally occurring protein in the brain and the N-terminal tripeptide of insulin-like growth factor 1 (IGF-1).1 Trofinetide was approved by the FDA on March 10, 2023, for the treatment of Rett syndrome,5,6 which is an X-linked neurodevelopmental disorder characterized by a range of cognitive, motor, and autonomic symptoms.1 Trofinetide is believed to work by reducing inflammation and apoptosis of neurons.2
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Trofinetide (DB06045)
- Weight
- Average: 315.326
Monoisotopic: 315.143035408 - Chemical Formula
- C13H21N3O6
- Synonyms
- glycyl-L-2-methylprolyl-L-glutamic acid
- Trofinetide
- External IDs
- NNZ 2566
- NNZ-2566
Pharmacology
- Indication
Trofinetide is indicated for the treatment of Rett syndrome in adults and pediatric patients two years of age and older.4
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Rett syndrome •••••••••••• ••••••••••• •••••• ••••••••• - Contraindications & Blackbox Warnings
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Trofinetide works to reduce and alleviate the symptoms of Rett syndrome.1 It is an analog of glypromate or glycine–proline–glutamate (GPE), a naturally occurring protein in the brain and the N-terminal tripeptide of insulin-like growth factor 1 (IGF-1). GPE exhibits neuroprotective properties: it protects neurons from glutamate-mediated excitotoxicity and oxidative stress at nanomolar concentrations. With a longer half-life than GPE, trofinetide is believed to exhibit similar neuroprotective properties.2
- Mechanism of action
Most cases of Rett syndrome are associated with loss-of-function mutations in a gene encoding methyl CpG binding protein 2 (MECP2), a DNA binding protein with a role in epigenetic regulation of gene expression.1 These mutations are believed to lead to synaptic immaturation in the cortex, aberrant metabolism of brain cholesterol resulting in abnormal neuronal development, and abnormal neuronal signaling.3 Rett syndrome more commonly occurs in girls than boys.1
The exact mechanism of action of trofinetide in Rett syndrome has not been fully elucidated.4 In mice studies, GPE improved motor and cardiorespiratory function, increased brain weight, and prolonged the lifespan in MECP2-deficient mice. As a GPE analog, trofinetide similarly attenuated apoptosis and reduced infarct size in a dose-dependent manner in a rat model of hypoxic insult.1,2 Trofinetide exerts a multi-faceted action to reduce inflammation, excitotoxicity-induced tissue damage, and apoptosis, thereby protecting the neurons and their surrounding infrastructure.2
- Absorption
Systemic exposure to trofinetide was dose-proportional across the studied dose range. The Tmax is about two to three hours after administration. Based on the mass balance study, at least 84% of the administered oral dose of 12,000 mg trofinetide was absorbed.4
A high-fat meal had negligible effects on drug exposure and reduced the Cmax by approximately 20%.4
- Volume of distribution
Following oral administration, the apparent volume of distribution of trofinetide in healthy adult subjects was approximately 80 L. Minimal to no accumulation was observed following multiple-dose administration.4
- Protein binding
Protein binding to human plasma is less than 6%.4
- Metabolism
Trofinetide is not significantly metabolized by CYP450 enzymes. Hepatic metabolism is not a significant route of trofinetide elimination.4
- Route of elimination
Trofinetide is primarily excreted in urine, with minor excretion in feces. Approximately 80% of the dose recovered in urine was in the unchanged parent drug form.4
- Half-life
The effective elimination half-life of orally administered trofinetide in healthy subjects is about 1.5 hours.4
- Clearance
No information is available.
- Adverse Effects
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There is no information available regarding acute toxicity (LD50) and overdose of trofinetide.
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbemaciclib The metabolism of Abemaciclib can be decreased when combined with Trofinetide. Acalabrutinib The metabolism of Acalabrutinib can be decreased when combined with Trofinetide. Acenocoumarol The metabolism of Acenocoumarol can be decreased when combined with Trofinetide. Albendazole The metabolism of Albendazole can be decreased when combined with Trofinetide. Alectinib The metabolism of Alectinib can be decreased when combined with Trofinetide. - Food Interactions
- Take with or without food. Food decreases Cmax of trofinetide but has negligible effects on total drug exposure.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Daybue Solution 200 mg/1mL Oral Acadia Pharmaceuticals Inc. 2022-12-31 Not applicable US 
Categories
- Drug Categories
- Amino Acids
- Amino Acids, Acidic
- Amino Acids, Dicarboxylic
- Amino Acids, Peptides, and Proteins
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (weak)
- Cytochrome P-450 Enzyme Inhibitors
- OATP1B1/SLCO1B1 Inhibitors
- OATP1B3 inhibitors
- Peptides
- UGT1A9 Inhibitors
- UGT2B15 Inhibitors
- UGT2B7 Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as oligopeptides. These are organic compounds containing a sequence of between three and ten alpha-amino acids joined by peptide bonds.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Oligopeptides
- Alternative Parents
- Glutamic acid and derivatives / N-acyl-L-alpha-amino acids / Alpha amino acid amides / Pyrrolidinecarboxamides / N-acylpyrrolidines / Heterocyclic fatty acids / Dicarboxylic acids and derivatives / Tertiary carboxylic acid amides / Secondary carboxylic acid amides / Amino acids show 6 more
- Substituents
- Aliphatic heteromonocyclic compound / Alpha-amino acid amide / Alpha-amino acid or derivatives / Alpha-oligopeptide / Amine / Amino acid / Amino acid or derivatives / Azacycle / Carbonyl group / Carboxamide group show 24 more
- Molecular Framework
- Aliphatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- Z2ME8F52QL
- CAS number
- 853400-76-7
- InChI Key
- BUSXWGRAOZQTEY-SDBXPKJASA-N
- InChI
- InChI=1S/C13H21N3O6/c1-13(5-2-6-16(13)9(17)7-14)12(22)15-8(11(20)21)3-4-10(18)19/h8H,2-7,14H2,1H3,(H,15,22)(H,18,19)(H,20,21)/t8-,13-/m0/s1
- IUPAC Name
- (2S)-2-{[(2S)-1-(2-aminoacetyl)-2-methylpyrrolidin-2-yl]formamido}pentanedioic acid
- SMILES
- C[C@]1(CCCN1C(=O)CN)C(=O)N[C@@H](CCC(O)=O)C(O)=O
References
- General References
- Neul JL, Percy AK, Benke TA, Berry-Kravis EM, Glaze DG, Peters SU, Jones NE, Youakim JM: Design and outcome measures of LAVENDER, a phase 3 study of trofinetide for Rett syndrome. Contemp Clin Trials. 2022 Mar;114:106704. doi: 10.1016/j.cct.2022.106704. Epub 2022 Feb 8. [Article]
- Bickerdike MJ, Thomas GB, Batchelor DC, Sirimanne ES, Leong W, Lin H, Sieg F, Wen J, Brimble MA, Harris PW, Gluckman PD: NNZ-2566: a Gly-Pro-Glu analogue with neuroprotective efficacy in a rat model of acute focal stroke. J Neurol Sci. 2009 Mar 15;278(1-2):85-90. doi: 10.1016/j.jns.2008.12.003. Epub 2009 Jan 20. [Article]
- Chahil G, Bollu PC: Rett Syndrome. . [Article]
- FDA Approved Drug Products: DAYBUE (trofinetide) Oral Solution [Link]
- FDA News: FDA approves first treatment for Rett Syndrome [Link]
- Acadia Pharmaceuticals: Acadia Pharmaceuticals Announces U.S. FDA Approval of DAYBUE™ (trofinetide) for the Treatment of Rett Syndrome in Adult and Pediatric Patients Two Years of Age and Older [Link]
- External Links
- ChemSpider
- 9493869
- 2632852
- ChEMBL
- CHEMBL197084
- Wikipedia
- Trofinetide
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data3 Completed Treatment Rett Syndrome 3 somestatus stop reason just information to hide 2 Completed Supportive Care Brain Injury 1 somestatus stop reason just information to hide 2 Completed Treatment Brain Injury 1 somestatus stop reason just information to hide 2 Completed Treatment Fragile X Syndrome 1 somestatus stop reason just information to hide 2 Completed Treatment Rett Syndrome 2 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Solution Oral 200 mg/1mL - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US11370755 No 2020-08-03 2040-08-03 US US9212204 No 2015-12-15 2032-01-27 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source boiling point (°C) 655.4±55 https://www.chemsrc.com/en/cas/853400-76-7_1470449.html logP -2.22 https://www.chemsrc.com/en/cas/853400-76-7_1470449.html - Predicted Properties
Property Value Source Water Solubility 10.4 mg/mL ALOGPS logP -3 ALOGPS logP -4.5 Chemaxon logS -1.5 ALOGPS pKa (Strongest Acidic) 3.27 Chemaxon pKa (Strongest Basic) 7.83 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 150.03 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 73.79 m3·mol-1 Chemaxon Polarizability 30.95 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-00kb-3294000000-6c459e44fa339bb29250 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-03di-1469000000-d318c29583bdca6a632c Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-000x-9660000000-d673dc51307932368489 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-03di-5890000000-92f4131aef1befd7a881 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-01q9-9710000000-85ed75b8b6ea7632871b Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-001l-9000000000-71a58144ad4ce8c12857 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Trofinetide was found to be an inhibitor of this enzyme in vitro.
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- FDA Approved Drug Products: DAYBUE (trofinetide) Oral Solution [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Trofinetide was found to be an inhibitor of this enzyme in vitro.
- General Function
- 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:15470161, PubMed:15472229, PubMed:18004212, PubMed:18052087, PubMed:18674515, PubMed:19545173). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol and estrone (PubMed:15472229). Also catalyzes the glucuronidation of 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 caderastan, 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:20610558). Also metabolizes mycophenolate, an immunosuppressive agent (PubMed:15470161, PubMed:18004212)
- Specific Function
- Enzyme binding
- Gene Name
- UGT1A9
- Uniprot ID
- O60656
- Uniprot Name
- UDP-glucuronosyltransferase 1A9
- Molecular Weight
- 59940.495 Da
References
- FDA Approved Drug Products: DAYBUE (trofinetide) Oral Solution [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Trofinetide was found to be an inhibitor of this enzyme in vitro.
- General Function
- 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:10702251, PubMed:15470161, PubMed:15472229, PubMed:17442341, PubMed:18674515, PubMed:18719240, PubMed:19022937, PubMed:23288867, PubMed:23756265, PubMed:26220143). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:15470161, PubMed:18674515, PubMed:23756265). Catalyzes the glucuronidation of endogenous steroid hormones such as androgens (epitestosterone, androsterone) and estrogens (estradiol, epiestradiol, estriol, catechol estrogens) (PubMed:15472229, PubMed:17442341, PubMed:18719240, PubMed:19022937, PubMed:2159463, PubMed:23288867, PubMed:26220143). Also regulates the levels of retinoic acid, a major metabolite of vitamin A involved in apoptosis, cellular growth and differentiation, and embryonic development (PubMed:10702251). Contributes to bile acid (BA) detoxification by catalyzing the glucuronidation of BA substrates, which are natural detergents for dietary lipids absorption (PubMed:23756265). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, caderastan and zolarsatan, drugs which can inhibit the effect of angiotensin II (PubMed:18674515). Also metabolizes mycophenolate, an immunosuppressive agent (PubMed:15470161)
- Specific Function
- Glucuronosyltransferase activity
- Gene Name
- UGT2B7
- Uniprot ID
- P16662
- Uniprot Name
- UDP-glucuronosyltransferase 2B7
- Molecular Weight
- 60720.15 Da
References
- FDA Approved Drug Products: DAYBUE (trofinetide) Oral Solution [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Trofinetide was found to be an inhibitor of this enzyme in vitro.
- General Function
- 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:16595710, PubMed:18719240, PubMed:23288867, PubMed:7835232, PubMed:9295060). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:7835232). Catalyzes the glucuronidation of endogenous steroid hormones such as androgens (testosterone, androsterone) and estrogens (estradiol, epiestradiol, estriol, catechol estrogens) (PubMed:16595710, PubMed:18719240, PubMed:23288867, PubMed:7835232, PubMed:9295060). Displays glucuronidation activity toward several classes of xenobiotic substrates, including phenolic compounds (eugenol, 4-nitrophenol, 4-hydroxybiphenyl) and phenylpropanoids (naringenin, coumarins) (PubMed:7835232). Catalyzes the glucuronidation of monoterpenoid alcohols such as borneol, menthol and isomenthol, a class of natural compounds used in essential oils (By similarity)
- Specific Function
- Glucuronosyltransferase activity
- Gene Name
- UGT2B15
- Uniprot ID
- P54855
- Uniprot Name
- UDP-glucuronosyltransferase 2B15
- Molecular Weight
- 61035.815 Da
References
- FDA Approved Drug Products: DAYBUE (trofinetide) Oral Solution [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Trofinetide was found to be an inhibitor of this transporter in vitro.
- General Function
- Mediates the Na(+)-independent uptake of organic anions (PubMed:10358072, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) (PubMed:10358072, PubMed:10601278, PubMed:10873595, PubMed:11159893, PubMed:12196548, PubMed:12568656, PubMed:15159445, PubMed:15970799, PubMed:16627748, PubMed:17412826, PubMed:19129463, PubMed:26979622). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Involved in the clearance of endogenous and exogenous substrates from the liver (PubMed:10358072, PubMed:10601278). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:10601278, PubMed:15159445, PubMed:15970799). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748). Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463)
- Specific Function
- Bile acid transmembrane transporter activity
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
References
- FDA Approved Drug Products: DAYBUE (trofinetide) Oral Solution [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Trofinetide was found to be an inhibitor of this transporter in vitro.
- General Function
- Mediates the Na(+)-independent uptake of organic anions (PubMed:10779507, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (17-beta-glucuronosyl estradiol, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate), as well as eicosanoid leukotriene C4, prostaglandin E2 and L-thyroxine (T4) (PubMed:10779507, PubMed:11159893, PubMed:12568656, PubMed:15159445, PubMed:17412826, PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463). Shows a pH-sensitive substrate specificity towards sulfated steroids, taurocholate and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Involved in the clearance of bile acids and organic anions from the liver (PubMed:22232210). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins) such as pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:15159445). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748)
- Specific Function
- Bile acid transmembrane transporter activity
- Gene Name
- SLCO1B3
- Uniprot ID
- Q9NPD5
- Uniprot Name
- Solute carrier organic anion transporter family member 1B3
- Molecular Weight
- 77402.175 Da
References
- FDA Approved Drug Products: DAYBUE (trofinetide) Oral Solution [Link]
Drug created at November 18, 2007 18:29 / Updated at April 07, 2023 13:12