Palovarotene

Identification

Summary

Palovarotene is a selective agonist of retinoic acid receptor gamma (RARγ) used to reduce heterotopic ossification in patients with Fibrodysplasia Ossificans Progressiva (FOP).

Generic Name
Palovarotene
DrugBank Accession Number
DB05467
Background

Fibrodysplasia Ossificans Progressiva (FOP), with an estimated worldwide prevalence of one in 2 million individuals, is an exceptionally rare genetic disorder.3 FOP is caused by a gain-of-function mutation in the ACVR1/ALK2 gene which results in progressive heterotopic ossification, a process wherein connective tissues (e.g. skeletal muscle, ligaments, tendons) are replaced with bone.3 The ossification occurring as a result of FOP is insidious and cumulative and is provoked during flare-ups or in response to injury. Treatment options for patients with FOP are extremely limited, although there has been substantial recent interest in novel treatments for this disease.3

Palovarotene is a selective agonist of retinoic acid receptor gamma (RARγ) belonging to a class of medications known as retinoids, similar in mechanism to drugs like tazarotene or trifarotene, which are derivatives of vitamin A. It first garnered interest as a potential treatment for emphysema but was eventually recognized as a potential novel therapy for patients with FOP.1,2,3 Agonists for retinoic acid receptors have been shown to inhibit chondrogenesis of heterotopic ossification in a transgenic mice model of FOP, with selective RARγ agonists (e.g. palovarotene) demonstrating the greatest efficacy.3

Palovarotene was approved for use in Canada in January 2022 for the management of heterotopic ossification (HO) in patients with FOP, representing the first global approval for any FOP therapy.4,6 It has been granted rare pediatric disease and breakthrough therapy designations from the US FDA, although a previously submitted NDA was withdrawn in August 2021 pending the resubmission of additional data analyses.5 On August 16, 2023, palovarotene was also approved by the FDA for the management of HO associated with FOP.9

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 414.549
Monoisotopic: 414.230728214
Chemical Formula
C27H30N2O2
Synonyms
  • Palovarotene
External IDs
  • R-667
  • R667
  • RG-667
  • RO3300074

Pharmacology

Indication

Palovarotene is indicated in Canada to reduce the formation of heterotopic ossification in adults and children (≥8 years old for females and ≥10 years old for males) with Fibrodysplasia Ossificans Progressiva (FOP) by Health Canada and FDA.4,7

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofHeterotopic ossification (ho)•••••••••••••••••• ••••••••••••••••
Management ofHeterotopic ossification (ho)•••••••••••••••••• ••••••••••••••••
Management ofHeterotopic ossification (ho)•••••••••••••••••• ••••••••••••••••
Management ofHeterotopic ossification (ho)•••••••••••••••••• ••••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Palovarotene exerts its pharmacologic effects by inhibiting the pathway(s) responsible for heterotopic ossification in patients with FOP.4 It is orally bioavailable and can be administered once daily, with allowances for short-term increases in dosage in the event of a flare-up.4

As with other retinoids, palovarotene can cause birth defects, and it should not be used by patients who are, or intend to become, pregnant. Palovarotene is contraindicated in patients of childbearing potential unless a number of pregnancy prevention strategies are met (e.g. effective contraception, regular pregnancy testing).4

Palovarotene may also cause a premature physeal closure in growing children. Physeal growth plates should be monitored every 3 months throughout therapy, or more frequently if evidence of adverse effects on growth are observed.4

At doses up to 2.5 times the maximum recommended dose, palovarotene does not prolong the QT interval to any clinically relevant extent.7

Palovarotene binds to retinoic acid receptor gamma (RARγ) with a 10-fold greater affinity compared to retinoic acid receptor alpha or beta. In animal models of Fibrodysplasia Ossificans Progressiva (BMP implant in WT mouse, Q207D mouse model, R206H mouse model), palovarotene decreased heterotopic ossification (HO) in a dose-dependent manner as well as inflammatory and fibroproliferative responses at the sites of injury. Additionally, palovarotene also outperformed corticosteroids in preventing HO, with a dexamethasone treatment of 4.4 mg/kg/day for 4 days demonstrating no clinical efficacy on heterotropic bone volume.8

Mechanism of action

The pathogenesis of FOP is driven by a gain-of-function mutation in the ACVR1/ALK2 gene encoding activin A receptor type 1 (ACVR1)/activin-like kinase 2 (ALK2), a bone morphogenetic protein type 1 receptor (BMPR-I).3 BMP signalling begins with the complexation of BMPR-II and BMPR-I, which initiates an intracellular signalling pathway mediated by phosphorylated SMAD proteins. The sustained and aberrant signalling caused by the gain-of-function mutation in ACVR1/ALK2 results in overactivation of the downstream SMAD1/5/8 signalling pathway, which in turn is thought to trigger the formation of ectopic chondrogenesis, osteogenesis, and joint fusion characteristic of FOP.3

Palovarotene is a selective agonist of retinoic acid receptor gamma (RARγ), a receptor expressed in chondrogenic cells and chondrocytes that acts as a transcriptional repressor.4 In binding to RARγ, palovarotene decreases BMP signalling and subsequently inhibits the SMAD1/5/8 signalling pathway. Palovarotene's interference with these pathways inhibits chondrogenesis and allows for normal muscle tissue repair to take place, ultimately reducing damage to muscle tissue.4

TargetActionsOrganism
ARetinoic acid receptor gamma
agonist
Humans
Absorption

Following oral administration of 20mg once daily in healthy adult subjects, the median Tmax was 4.6 hours, the mean Cmax was 140 ng/mL, and the mean AUC(0-τ) was 942 ng*hr/mL.4 At steady-state, the mean trough concentration of palovarotene was 3.5 ng/mL.4

The administration of palovarotene with a high-fat, high-calorie meal resulted in an approximate 40% increase in AUC, an approximate 16% increase in Cmax, and a delay in Tmax by approximately 2 hours when compared to its administration under fasting conditions.4

Volume of distribution

The mean (SD) apparent volume of distribution (Vd/F) is 237 (± 90.1) L following the administration of a single 20 mg dose with food.7

Protein binding

The protein binding of palovarotene is 97.9% to 99.6% in vitro.7

Metabolism

Palovarotene undergoes extensive metabolism by CYP3A4 and, to a lesser extent, CYP2C8 and CYP2C19.4 Five metabolites have been observed in plasma: M1 (6,7-dihydroxy), M2 (6-hydroxy), M3 (7-hydroxy), M4a (6-oxo), and M4b (7-oxo).4 Following oral administration of palovarotene, the parent drug and its four main metabolites (M2, M3, M4a, and M4b) account for approximately 40% of total plasma exposure.4

The metabolites of palovarotene are functionally inactive, with M3 and M4b carrying 1.7% and 4.2% of the activity of their parent compound, respectively.4

Route of elimination

Following the administration of a 1mg radiolabeled dose of palovarotene in healthy subjects, approximately 97.1% of the administered radioactivity was recovered in the feces, with only 3.2% recovered in the urine.4

Half-life

The mean elimination half-life of palovarotene at steady-state is 8.7 hours.4

Clearance

The apparent total body clearance of palovarotene is approximately 19.9 L/h.4

Adverse Effects
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Toxicity

Palovarotene is contraindicated during pregnancy. Based on the findings in animal studies and class effects of retinoids, SOHONOS can cause fetal harm when administered during pregnancy. In animal reproduction studies, oral administration of palovarotene to pregnant rats during the period of organogenesis resulted in multiple fetal malformations typical of retinoids (e.g., cleft palate, malformed skull bone, shortening of the long bones) at doses ≥0.25 mg/kg/day (less than the clinical exposure). There are no available human data on palovarotene use in pregnant women. If pregnancy occurs during treatment with palovarotene, discontinue treatment immediately and refer the patient to an obstetrician/gynecologist or other specialist experienced in reproductive toxicity for further evaluation and counseling.7

No clinical experience with an overdose of palovarotene has been reported. Palovarotene is a derivative of vitamin A. In case of accidental overdose, signs of hypervitaminosis A could appear, including severe headache, nausea or vomiting, drowsiness, irritability, and pruritus. Any overdose should be treated with supportive care according to the signs and symptoms exhibited by the patient. If an overdose is suspected, patients should be treated with supportive care as clinically indicated.7

Long-term studies to assess the carcinogenic potential of palovarotene have not been conducted. Palovarotene and its metabolites were negative in the vitro bacterial reverse mutation (Ames) assay and an in vitro micronucleus assay in primary human lymphocyte. Palovarotene did not have any clastogenic effect in the in vivo mouse micronucleus study.7

Palovarotene effects on fertility and reproductive function were assessed in male and female rats. In a female rat fertility study, palovarotene was orally administered to females for 14 days prior to mating with drug naïve males and up to GD 7 at the dose levels of 0.3, 1, and 3 mg/kg/day. Palovarotene caused prolonged periods of diestrous and reduced ovulation rate, resulting in lower numbers of implantation sites and live embryos at 3 mg/kg/day, a dose associated with maternal toxicity.7

In a male rat fertility study, palovarotene was orally administered prior to mating, during mating, and up to scheduled euthanasia (approximately 11 weeks in total) at 0.3, 1, and 3 mg/kg/day. Palovarotene did not cause adverse effects on mating, fertility indices, conception rate, reproductive organ weights, or sperm parameters up to 1 mg/kg/day (less than the clinical exposure). Males did not tolerate 3 mg/kg/day, as it produced severe systemic toxicity including deaths, adverse skin and hair coat clinical signs, and substantially reduced body weight.7

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
AbametapirThe serum concentration of Palovarotene can be increased when it is combined with Abametapir.
AbemaciclibThe metabolism of Abemaciclib can be increased when combined with Palovarotene.
AcalabrutinibThe metabolism of Acalabrutinib can be increased when combined with Palovarotene.
AcenocoumarolThe metabolism of Acenocoumarol can be increased when combined with Palovarotene.
AcitretinThe risk or severity of adverse effects can be increased when Acitretin is combined with Palovarotene.
Food Interactions
  • Avoid grapefruit products. Grapefruit-containing products may inhibit the CYP3A4 activity responsible for palovarotene metabolism.
  • Avoid St. John's Wort. The significant induction of CYP3A4 metabolism caused by St. John's wort may decrease the effectiveness of palovarotene.
  • Take with food. Co-administration with food increases the oral absorption of palovarotene.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
SohonosCapsule10 mgOralIpsen Biopharmaceuticals Canada Inc2022-06-20Not applicableCanada flag
SohonosCapsule1.5 mgOralIpsen Biopharmaceuticals Canada Inc2022-06-20Not applicableCanada flag
SohonosCapsule10 mg/1OralIpsen Biopharmaceuticals, Inc.2023-08-16Not applicableUS flag
SohonosCapsule1.5 mg/1OralIpsen Biopharmaceuticals, Inc.2023-08-16Not applicableUS flag
SohonosCapsule5 mgOralIpsen Biopharmaceuticals Canada Inc2022-06-20Not applicableCanada flag

Categories

ATC Codes
M09AX11 — Palovarotene
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as stilbenes. These are organic compounds containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are derived from the common phenylpropene (C6-C3) skeleton building block. The introduction of one or more hydroxyl groups to a phenyl ring lead to stilbenoids.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Stilbenes
Sub Class
Not Available
Direct Parent
Stilbenes
Alternative Parents
Tetralins / Benzoic acids / Styrenes / Benzoyl derivatives / Pyrazoles / Heteroaromatic compounds / Carboxylic acids / Azacyclic compounds / Organooxygen compounds / Organonitrogen compounds
show 2 more
Substituents
Aromatic heteropolycyclic compound / Azacycle / Azole / Benzenoid / Benzoic acid / Benzoic acid or derivatives / Benzoyl / Carboxylic acid / Carboxylic acid derivative / Heteroaromatic compound
show 12 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
28K6I5M16G
CAS number
410528-02-8
InChI Key
YTFHCXIPDIHOIA-DHZHZOJOSA-N
InChI
InChI=1S/C27H30N2O2/c1-26(2)12-13-27(3,4)24-17-22(18-29-15-5-14-28-29)21(16-23(24)26)11-8-19-6-9-20(10-7-19)25(30)31/h5-11,14-17H,12-13,18H2,1-4H3,(H,30,31)/b11-8+
IUPAC Name
4-[(1E)-2-{5,5,8,8-tetramethyl-3-[(1H-pyrazol-1-yl)methyl]-5,6,7,8-tetrahydronaphthalen-2-yl}ethenyl]benzoic acid
SMILES
CC1(C)CCC(C)(C)C2=C1C=C(CN1C=CC=N1)C(\C=C\C1=CC=C(C=C1)C(O)=O)=C2

References

Synthesis Reference

Desjardins, C., Grogan, D. R., Packman, J. N., & Harnett, M. (2017). Methods for treating heterotopic ossification (WO2017210792A1). World Intellectual Property Organization. https://patents.google.com/patent/WO2017210792A1

General References
  1. Chiu YY, Roth MD, Kolis S, Rogovitz D, Davies B: Pharmacokinetics of a novel agent, R667, in patients with emphysema. Br J Clin Pharmacol. 2007 May;63(5):527-33. Epub 2007 Feb 23. [Article]
  2. Brennan B, Chiu Y, Berthelon L, Kolis S, Davies B: Effect of age and gender on the pharmacokinetics of R667, a novel agent for the treatment of emphysema, in healthy volunteers. J Pharm Pharm Sci. 2007;10(1):9-16. [Article]
  3. Kitoh H: Clinical Aspects and Current Therapeutic Approaches for FOP. Biomedicines. 2020 Sep 2;8(9). pii: biomedicines8090325. doi: 10.3390/biomedicines8090325. [Article]
  4. Health Canada Product Monograph: Sohonos (palovarotene) capsules for oral use [Link]
  5. Ipsen: Ipsen announces withdrawal of palovarotene NDA, confirming intention to re-submit following additional data analyses [Link]
  6. Ipsen Press Release: Health Canada approves Ipsen’s Sohonos (palovarotene capsules) as the first approved treatment for fibrodysplasia ossificans progressiva [Link]
  7. FDA Approved Drug Products: SOHONOS (palovarotene) capsules, for oral use [Link]
  8. PALOVAROTENE FOR THE PREVENTION OF HETEROTOPIC OSSIFICATION IN ADULTS AND CHILDREN (≥ 8 YEARS OF AGE FOR FEMALES AND ≥ 10 YEARS OF AGE FOR MALES) WITH FIBRODYSPLASIA OSSIFICANS PROGRESSIVA (FOP) [Link]
  9. US FDA approves Ipsen’s SohonosTM (palovarotene) capsules, the first and only treatment for people with fibrodysplasia ossificans progressiva [Link]
ChemSpider
8470763
ChEBI
188559
ChEMBL
CHEMBL2105648
ZINC
ZINC000038467831
Wikipedia
Palovarotene

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentFibrodysplasia Ossificans Progressiva (FOP)1
3CompletedTreatmentFibrodysplasia Ossificans Progressiva (FOP)1
2CompletedTreatmentFibrodysplasia Ossificans Progressiva (FOP)3
2TerminatedTreatmentExostoses, Multiple Hereditary1
2TerminatedTreatmentFibrodysplasia Ossificans Progressiva (FOP)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
CapsuleOral1 mg/1
CapsuleOral1 mg
CapsuleOral1.5 mg/1
CapsuleOral1.5 mg
CapsuleOral10 mg/1
CapsuleOral10 mg
CapsuleOral2.5 mg/1
CapsuleOral2.5 mg
CapsuleOral5 mg/1
CapsuleOral5 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US11622959No2017-06-082037-06-08US flag
US10864194No2020-12-152037-06-08US flag
US10292954No2019-05-212031-08-31US flag
US9789074No2017-10-172031-08-31US flag
US9314439No2016-04-192031-08-31US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility0.04 μg/mLL39990
Predicted Properties
PropertyValueSource
Water Solubility0.000344 mg/mLALOGPS
logP6.94ALOGPS
logP6.75Chemaxon
logS-6.1ALOGPS
pKa (Strongest Acidic)4.13Chemaxon
pKa (Strongest Basic)2.07Chemaxon
Physiological Charge-1Chemaxon
Hydrogen Acceptor Count3Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area55.12 Å2Chemaxon
Rotatable Bond Count5Chemaxon
Refractivity137.81 m3·mol-1Chemaxon
Polarizability47.96 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
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/MSsplash10-0002-0009000000-a6ce01a8a83cafa8e72f
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-03di-0002900000-5ee0f1f1892b39eac36c
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-02t9-0019200000-e2797bb29192f110fd60
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0002-0009000000-f431e12383f698099565
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0pbc-1149000000-22c2a613333184727f8c
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-004j-2119000000-ad42854cf8ca0e5d8232
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-200.17332
predicted
DeepCCS 1.0 (2019)
[M+H]+202.5689
predicted
DeepCCS 1.0 (2019)
[M+Na]+208.48141
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expressi...
Gene Name
RARG
Uniprot ID
P13631
Uniprot Name
Retinoic acid receptor gamma
Molecular Weight
50341.405 Da
References
  1. Health Canada Product Monograph: Sohonos (palovarotene) capsules for oral use [Link]
  2. FDA Approved Drug Products: SOHONOS (palovarotene) capsules, for oral use [Link]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
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. Health Canada Product Monograph: Sohonos (palovarotene) capsules for oral use [Link]
  2. FDA Approved Drug Products: SOHONOS (palovarotene) capsules, for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
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. Health Canada Product Monograph: Sohonos (palovarotene) capsules for oral use [Link]
  2. FDA Approved Drug Products: SOHONOS (palovarotene) capsules, for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
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. Health Canada Product Monograph: Sohonos (palovarotene) capsules for oral use [Link]
  2. FDA Approved Drug Products: SOHONOS (palovarotene) capsules, for oral use [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: SOHONOS (palovarotene) capsules, for oral use [Link]

Transporters

Kind
Protein
Organism
Humans
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
References
  1. PALOVAROTENE FOR THE PREVENTION OF HETEROTOPIC OSSIFICATION IN ADULTS AND CHILDREN (≥ 8 YEARS OF AGE FOR FEMALES AND ≥ 10 YEARS OF AGE FOR MALES) WITH FIBRODYSPLASIA OSSIFICANS PROGRESSIVA (FOP) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
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
References
  1. PALOVAROTENE FOR THE PREVENTION OF HETEROTOPIC OSSIFICATION IN ADULTS AND CHILDREN (≥ 8 YEARS OF AGE FOR FEMALES AND ≥ 10 YEARS OF AGE FOR MALES) WITH FIBRODYSPLASIA OSSIFICANS PROGRESSIVA (FOP) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
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
References
  1. PALOVAROTENE FOR THE PREVENTION OF HETEROTOPIC OSSIFICATION IN ADULTS AND CHILDREN (≥ 8 YEARS OF AGE FOR FEMALES AND ≥ 10 YEARS OF AGE FOR MALES) WITH FIBRODYSPLASIA OSSIFICANS PROGRESSIVA (FOP) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Secondary active organic cation transmembrane transporter activity
Specific Function
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
References
  1. PALOVAROTENE FOR THE PREVENTION OF HETEROTOPIC OSSIFICATION IN ADULTS AND CHILDREN (≥ 8 YEARS OF AGE FOR FEMALES AND ≥ 10 YEARS OF AGE FOR MALES) WITH FIBRODYSPLASIA OSSIFICANS PROGRESSIVA (FOP) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
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
References
  1. PALOVAROTENE FOR THE PREVENTION OF HETEROTOPIC OSSIFICATION IN ADULTS AND CHILDREN (≥ 8 YEARS OF AGE FOR FEMALES AND ≥ 10 YEARS OF AGE FOR MALES) WITH FIBRODYSPLASIA OSSIFICANS PROGRESSIVA (FOP) [Link]

Drug created at January 31, 2022 20:47 / Updated at August 23, 2023 22:19