Explore a selection of our essential drug information below, or:
Identification
- Summary
Berotralstat is an inhibitor of plasma kallikrein used for prophylaxis of angioedema attacks in patients with hereditary angioedema.
- Brand Names
- Orladeyo
- Generic Name
- Berotralstat
- DrugBank Accession Number
- DB15982
- Background
Berotralstat is a selective inhibitor of plasma kallikrein used in the prophylaxis of attacks of hereditary angioedema (HAE).5 It works by blocking the enzymatic activity of plasma kallikrein in releasing bradykinin, the major biologic peptide that promotes swelling and pain associated with attacks of HAE.3 Berotralstat is strictly used to prevent, but not treat, these attacks.4
Developed by BioCryst Pharmaceuticals, berotralstat is marketed under the name Orladeyo as oral capsules.1 Berotralstat was first approved by the FDA on December 3, 2020, as the first once-daily oral therapy to prevent angioedema attacks of HAE in adults and pediatric patients 12 years and older.5 Berotralstat was approved by the European Commission on April 30, 2021 7 and by Health Canada on June 06, 2022.6
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Berotralstat (DB15982)
- Weight
- Average: 562.573
Monoisotopic: 562.210422133 - Chemical Formula
- C30H26F4N6O
- Synonyms
- (+)-1-(3-(aminomethyl) phenyl)-N-(5-((3-cyanophenyl)(cyclopropylmethylamino)methyl)-2-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide dihydrochloride
- (R)-1-(3-(aminomethyl) phenyl)-N-(5-((3- cyanophenyl)(cyclopropylmethylamino)methyl)-2-fluorophenyl)-3- (trifluoromethyl)-1H-pyrazole-5-carboxamide dihydrochloride
- 2-[3-(aminomethyl)phenyl]-N-[5-[(R)-(3-cyanophenyl)-(cyclopropylmethylamino)methyl]-2-fluorophenyl]-5-(trifluoromethyl)pyrazole-3-carboxamide
- BCX7353
- Berotralstat
- External IDs
- BCX 7353
- BCX-7353
- BCX7353
- WHO 10907
Pharmacology
- Indication
Berotralstat is indicated for prophylaxis of attacks of hereditary angioedema (HAE) in adults and pediatric patients 12 years and older. It is not used for the treatment of acute HAE attacks.5,7,8
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 Prophylaxis of Acute attack of hereditary angioedema •••••••••••• •••••• ••••••••• ••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Berotralstat prevents angioedema attacks by inhibiting plasma kallikrein, thereby regulating excess bradykinin generation in patients with hereditary angioedema (HAE). It had a fast onset of action, long duration of action, and acceptable tolerance in clinical trials.1 Berotralstat inhibits plasma kallikrein in a concentration-dependent.5 In clinical trials, berotralstat reduced HAE attack rates at 24 weeks, and its effects sustained through 48 weeks.4
In clinical trials, doses of berotralstat higher than 150 mg once daily led to QT Prolongation in a concentration-dependent manner.5
- Mechanism of action
Hereditary angioedema (HAE) is a rare genetic disorder associated with severe swelling of the skin and upper airway.1 It is caused by mutations in the regulatory or coding regions of the gene that encodes C1 inhibitor (SERPING1), which result in either a deficiency (type I) or dysfunction (type II) of C1 inhibitor (C1 esterase inhibitor, C1-INH). C1 inhibitor is a serine protease inhibitor that normally regulates bradykinin production by covalently binding to and inactivating plasma kallikrein.2
Plasma kallikrein is a protease that cleaves high-molecular-weight-kininogen (HMWK) to generate cleaved HMWK (cHMWK).5 During HAE attacks, the levels of plasma kallikrein fall, leading to the cleavage of high-molecular-weight-kininogen and the release of bradykinin, a potent vasodilator that increases vascular permeability. Bradykinin plays a major role in promoting edema and pain associated with HAE.3,5 Patients with HAE cannot properly regulate plasma kallikrein activity due to the deficiency or dysfunction of a serum inhibitor of C1 inhibitor, leading to uncontrolled increases in plasma kallikrein activity and recurrent angioedema attacks.5 Berotralstat is a potent inhibitor of plasma kallikrein that works by binding to plasma kallikrein and blocking its proteolytic activity, thereby controlling excess bradykinin generation.2,5
Target Actions Organism APlasma kallikrein inhibitorHumans - Absorption
The steady-state of berotralstat is reached within 6 to 12 days following initial administration. After once-daily administration, the Cmax and AUC of berotralstat at steady-state is approximately five times that of the drug after a single dose. Following oral administration of berotralstat once-daily, the steady-state Cmax was 158 ng/mL (range: 110 to 234 ng/mL) at the dose of 150 mg and 97.8 ng/mL (range: 63 to 235 ng/mL) at the dose of 110 mg. The area under the curve over the dosing interval (AUCtau) was 2770 nghr/mL (range: 1880 to 3790 nghr/mL) and 1600 nghr/mL (range: 950 to 4170 nghr/mL) at the dose of 110 mg. The median Tmax is 2 hours in a fasted state and a high-fat meal delays the Tmax to 5 hours. The Tmax can range from 1 to 8 hours.5
- Volume of distribution
The blood to plasma ratio was approximately 0.92 following a single 300 mg dose administration of radiolabeled berotralstat.5
- Protein binding
Plasma protein binding is approximately 99%.5
- Metabolism
Berotralstat is metabolized by CYP2D6 and CYP3A4. The metabolic pathway and the metabolites of berotralstat have not yet been characterized. Following a single oral dose administration of 300 mg radiolabeled berotralstat, about 34% of the total plasma radioactivity accounted for the unchanged drug while about eight detectable metabolites accounted for 1.8 to 7.8% of the total radioactivity.5
- Route of elimination
Following a single oral dose administration of 300 mg radiolabeled berotralstat, approximately 9% of the drug was excreted in the urine, where 1.8 to 4.7% of the total radiolabeled compound accounted for the unchanged parent drug. About 79% of the drug was excreted in feces.5
- Half-life
Following a single oral dose administration of 300 mg radiolabeled berotralstat, the median elimination half-life of berotralstat was approximately 93 hours, ranging from 39 to 152 hours.5
- Clearance
There is no information on the clearance rate.
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
There is no information on the LD50 or overdose of berotralstat.
- 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 software1,2-Benzodiazepine The metabolism of 1,2-Benzodiazepine can be decreased when combined with Berotralstat. Abemaciclib The serum concentration of Berotralstat can be increased when it is combined with Abemaciclib. Abiraterone The metabolism of Abiraterone can be decreased when combined with Berotralstat. Abrocitinib The serum concentration of Berotralstat can be increased when it is combined with Abrocitinib. Acalabrutinib The serum concentration of Acalabrutinib can be increased when it is combined with Berotralstat. - Food Interactions
- Take with food. This is instructed by the prescribing information of berotralstat. A high-fat meal had no significant effects on the Cmax and AUC of berotralstat, but the Tmax was delayed by 3 hours.
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.- Product Ingredients
Ingredient UNII CAS InChI Key Berotralstat hydrochloride 88SH1NBL2B 1809010-52-3 XFZLBLTUANGZBD-QDSLRZTOSA-N - International/Other Brands
- Orladeyo (BioCryst)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Orladeyo Capsule 150 mg Oral Biocryst Ireland Limited 2022-06-06 Not applicable EU 
Orladeyo Capsule 150 mg/1 Oral BioCryst Pharmaceuticals Inc. 2020-12-04 Not applicable US 
Orladeyo Capsule 150 mg Oral BioCryst Pharmaceuticals Inc. 2022-09-06 Not applicable Canada 
Orladeyo Capsule 150 mg Oral Biocryst Ireland Limited 2022-06-06 Not applicable EU Orladeyo Capsule 110 mg/1 Oral BioCryst Pharmaceuticals Inc. 2020-12-04 Not applicable US
Categories
- ATC Codes
- B06AC06 — Berotralstat
- Drug Categories
- BCRP/ABCG2 Substrates
- Blood and Blood Forming Organs
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (moderate)
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (moderate)
- Cytochrome P-450 Enzyme Inhibitors
- Drugs Used in Hereditary Angioedema
- Enzyme Inhibitors
- Kallikrein Inhibitors
- Kallikreins, antagonists & inhibitors
- Moderate Risk QTc-Prolonging Agents
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- Plasma Kallikrein Inhibitor
- Protease Inhibitors
- QTc Prolonging Agents
- Serine Protease Inhibitors
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- XZA0KB1BDQ
- CAS number
- 1809010-50-1
- InChI Key
- UXNXMBYCBRBRFD-MUUNZHRXSA-N
- InChI
- InChI=1S/C30H26F4N6O/c31-24-10-9-22(28(37-17-18-7-8-18)21-5-1-3-19(11-21)15-35)13-25(24)38-29(41)26-14-27(30(32,33)34)39-40(26)23-6-2-4-20(12-23)16-36/h1-6,9-14,18,28,37H,7-8,16-17,36H2,(H,38,41)/t28-/m1/s1
- IUPAC Name
- 1-[3-(aminomethyl)phenyl]-N-{5-[(R)-(3-cyanophenyl)[(cyclopropylmethyl)amino]methyl]-2-fluorophenyl}-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide
- SMILES
- NCC1=CC(=CC=C1)N1N=C(C=C1C(=O)NC1=CC(=CC=C1F)[C@H](NCC1CC1)C1=CC=CC(=C1)C#N)C(F)(F)F
References
- General References
- Hwang JR, Hwang G, Johri A, Craig T: Oral plasma kallikrein inhibitor BCX7353 for treatment of hereditary angioedema. Immunotherapy. 2019 Dec;11(17):1439-1444. doi: 10.2217/imt-2019-0128. Epub 2019 Oct 22. [Article]
- Aygoren-Pursun E, Bygum A, Grivcheva-Panovska V, Magerl M, Graff J, Steiner UC, Fain O, Huissoon A, Kinaciyan T, Farkas H, Lleonart R, Longhurst HJ, Rae W, Triggiani M, Aberer W, Cancian M, Zanichelli A, Smith WB, Baeza ML, Du-Thanh A, Gompels M, Gonzalez-Quevedo T, Greve J, Guilarte M, Katelaris C, Dobo S, Cornpropst M, Clemons D, Fang L, Collis P, Sheridan W, Maurer M, Cicardi M: Oral Plasma Kallikrein Inhibitor for Prophylaxis in Hereditary Angioedema. N Engl J Med. 2018 Jul 26;379(4):352-362. doi: 10.1056/NEJMoa1716995. [Article]
- Schmaier AH: Plasma Prekallikrein: Its Role in Hereditary Angioedema and Health and Disease. Front Med (Lausanne). 2018 Jan 25;5:3. doi: 10.3389/fmed.2018.00003. eCollection 2018. [Article]
- Drugs.com: FDA Approves Orladeyo [Link]
- FDA Approved Drug Products: ORLADEYO (berotralstat) capsules, for oral use [Link]
- GlobeNewswire News Release: BioCryst Announces Health Canada has Authorized ORLADEYO® (berotralstat), the Only Oral Treatment for the Prevention of Hereditary Angioedema Attacks [Link]
- EMA Approved Drug Products: Orladeyo (berotralstat) oral capsules [Link]
- Health Canada Approved Drug Products: ORLADEYO (Berotralstat) oral capsules [Link]
- External Links
- Human Metabolome Database
- HMDB0304862
- ChemSpider
- 81368516
- 2467540
- PDBe Ligand
- 0RI
- Wikipedia
- Berotralstat
- PDB Entries
- 7n7x
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 dataNot Available Approved for Marketing Not Available Hereditary Angioedema (HAE) / Prophylaxis 1 somestatus stop reason just information to hide 3 Active Not Recruiting Prevention Hereditary Angioedema (HAE) 1 somestatus stop reason just information to hide 3 Active Not Recruiting Treatment Hereditary Angioedema (HAE) / Pediatric 1 somestatus stop reason just information to hide 3 Completed Prevention Hereditary Angioedema (HAE) 2 somestatus stop reason just information to hide 2 Completed Prevention Hereditary Angioedema (HAE) 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral 110 mg/1 Capsule Oral 150 mg Capsule Oral 150 mg/1 - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US10125102 No 2018-11-13 2035-03-09 US US10689346 No 2020-06-23 2035-03-09 US US10662160 No 2020-05-26 2039-11-01 US US10329260 No 2019-06-25 2035-03-09 US US11117867 No 2021-09-14 2039-11-01 US US11230530 No 2015-03-09 2035-03-09 US US11618733 No 2019-11-01 2039-11-01 US US11708333 No 2015-03-09 2035-03-09 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00238 mg/mL ALOGPS logP 4.8 ALOGPS logP 5.58 Chemaxon logS -5.4 ALOGPS pKa (Strongest Acidic) 13.35 Chemaxon pKa (Strongest Basic) 9.29 Chemaxon Physiological Charge 2 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 108.76 Å2 Chemaxon Rotatable Bond Count 10 Chemaxon Refractivity 149.32 m3·mol-1 Chemaxon Polarizability 55.92 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Participates in the surface-dependent activation of blood coagulation. Activates, in a reciprocal reaction, coagulation factor XII/F12 after binding to negatively charged surfaces. Releases bradykinin from HMW kininogen and may also play a role in the renin-angiotensin system by converting prorenin into renin
- Specific Function
- serine-type endopeptidase activity
- Gene Name
- KLKB1
- Uniprot ID
- P03952
- Uniprot Name
- Plasma kallikrein
- Molecular Weight
- 71342.175 Da
References
- Hwang JR, Hwang G, Johri A, Craig T: Oral plasma kallikrein inhibitor BCX7353 for treatment of hereditary angioedema. Immunotherapy. 2019 Dec;11(17):1439-1444. doi: 10.2217/imt-2019-0128. Epub 2019 Oct 22. [Article]
- Aygoren-Pursun E, Bygum A, Grivcheva-Panovska V, Magerl M, Graff J, Steiner UC, Fain O, Huissoon A, Kinaciyan T, Farkas H, Lleonart R, Longhurst HJ, Rae W, Triggiani M, Aberer W, Cancian M, Zanichelli A, Smith WB, Baeza ML, Du-Thanh A, Gompels M, Gonzalez-Quevedo T, Greve J, Guilarte M, Katelaris C, Dobo S, Cornpropst M, Clemons D, Fang L, Collis P, Sheridan W, Maurer M, Cicardi M: Oral Plasma Kallikrein Inhibitor for Prophylaxis in Hereditary Angioedema. N Engl J Med. 2018 Jul 26;379(4):352-362. doi: 10.1056/NEJMoa1716995. [Article]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- FDA Approved Drug Products: ORLADEYO (berotralstat) capsules, for oral use [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- Curator comments
- According to the prescribing information of berotralstat, berotralstat at a dose of 150 mg is a moderate inhibitor of CYP2D6.
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, 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) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
- Specific Function
- anandamide 11,12 epoxidase activity
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- FDA Approved Drug Products: ORLADEYO (berotralstat) capsules, for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- Curator comments
- According to the prescribing information of berotralstat, berotralstat at a dose of 150 mg is a moderate inhibitor of CYP3A4.
- 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: ORLADEYO (berotralstat) capsules, for oral use [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- Curator comments
- According to the prescribing information of berotralstat, berotralstat at a dose of 300 mg is a P-gp inhibitor.
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- FDA Approved Drug Products: ORLADEYO (berotralstat) capsules, for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- Broad substrate specificity ATP-binding cassette transporter ABCG2
- Molecular Weight
- 72313.47 Da
References
- FDA Approved Drug Products: ORLADEYO (berotralstat) capsules, for oral use [Link]
Drug created at December 08, 2020 18:56 / Updated at March 25, 2023 04:38