Abaloparatide
Identification
- Summary
Abaloparatide is a parathyroid hormone-related protein (PTHrP) analog used for the treatment of osteoporosis in postmenopausal women with a high risk of fracture.
- Brand Names
- Tymlos
- Generic Name
- Abaloparatide
- DrugBank Accession Number
- DB05084
- Background
Abaloparatide is an analog of PTHrP (parathyroid hormone-related protein). It was approved in April 28, 2017 by the FDA (as Tymlos) for the treatment of postmenopausal women with osteoporosis at high risk for fracture. Abaloparatide is a synthetic peptide that is related to hPTHrP and has demonstrated in preclinical testing the potential to widen the anabolic window for bone therapeutics, stimulating bone formation with a limited effect on bone resorption and mineral mobilization. This could enable improved convenience over currently available anabolic therapies, resulting in greater compliance and, ultimately, greater benefit to patients.
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Hormones - Protein Chemical Formula
- C174H300N56O49
- Protein Average Weight
- 3961.0 Da
- Sequences
>Abaloparatide N-terminal peptide sequence AVSEHQLLHDKGKSIQDLRRRELLEKLLXKLHTA
Download FASTA Format- Synonyms
- Abaloparatide
- External IDs
- BA-058
- BA058
- BIM-44058
- BIM44058
Pharmacology
- Indication
Investigated for use/treatment in postmenopausal osteoporosis to reduce vertebral and/or non-vertebral fractures.
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- Contraindications & Blackbox Warnings
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Abaloparatide (BA058), a proprietary analog of human parathyroid hormone-related protein (hPTHrP), is currently undergoing clinical trials by the company for the treatment of osteoporosis in postmenopausal women. PTHrP is a critical peptide for promoting new bone formation, with a distinct role from parathyroid hormone, or PTH, which primarily regulates calcium homeostasis and bone resorption. Clinical studies show increased bone mineral density (BMD) and levels of bone formation markers in a dose-response relationship.
- Mechanism of action
In target cells, abaloparatide acts as an agonist on PTH type 1 receptor (PTH1R) and activates both G protein–mediated cAMP signaling and β-arrestin-mediated ERK-1/2 signaling pathways with similar potency [A19105]. Abaloparatide binds to RG conformation of PTH1R with greater selectivity that results in more transient cell signalling responses.
Target Actions Organism AParathyroid hormone/parathyroid hormone-related peptide receptor ligandHumans - Absorption
The time it takes to reach peak concentration following subcutaneous administration of 80 mcg abaloparatide ranges from 0.25 to 0.52 hr, with the median time of 0.51hr. The bioavailability in healthy women is 36% following administration.
- Volume of distribution
Vd is approximately 50L.
- Protein binding
In vitro plasma protein binding is approximately 70%.
- Metabolism
Abaloparatide is metabolized into smaller peptide fragments via non-specific proteolytic degradation.
- Route of elimination
Metabolized products are mainly eliminated via renal excretion. Patients with severe renal impairment should be monitored with increased risk of adverse effects however there are no recommended dosage adjustments in patients with mild, moderate or severe renal impairment.
- Half-life
The mean (SD) half-life if 1.7 (0.7) hrs.
- Clearance
Not Available
- Adverse Effects
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Abaloparatide has shown to induce higher incidences of osteosarcoma in a dose-dependent manner in a 2 year carcinogenicity study with female and male rats. This correlation is not known to be reflected in humans, however patients with increased risk of osteosarcoma including Paget's disease, open epiphyses, and skeletal malignancies should avoid this treatment. Abaloparatide may also cause hypercalcemia so should be avoided in patients with pre-existing conditions of primary hyperthyroidism or hypercalcemia. Overdose is commonly associated with hypercalcemia, nausea, vomiting, dizziness, tachycardia, orthostatic hypotension and headache. There is no known antidote for abaloparatide.
- 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 softwareAcalabrutinib The therapeutic efficacy of Abaloparatide can be decreased when used in combination with Acalabrutinib. Acebutolol The risk or severity of adverse effects can be increased when Acebutolol is combined with Abaloparatide. Acetohexamide The therapeutic efficacy of Acetohexamide can be decreased when used in combination with Abaloparatide. Afatinib The therapeutic efficacy of Abaloparatide can be decreased when used in combination with Afatinib. Aldesleukin The therapeutic efficacy of Abaloparatide can be decreased when used in combination with Aldesleukin. Alectinib The therapeutic efficacy of Abaloparatide can be decreased when used in combination with Alectinib. Aminosalicylic acid The therapeutic efficacy of Abaloparatide can be decreased when used in combination with Aminosalicylic acid. Amphetamine The risk or severity of adverse effects can be increased when Amphetamine is combined with Abaloparatide. Avapritinib The therapeutic efficacy of Abaloparatide can be decreased when used in combination with Avapritinib. Axitinib The therapeutic efficacy of Abaloparatide can be decreased when used in combination with Axitinib. 
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- Administer vitamin supplements. If dietary intake is inadequate, patients should receive supplemental calcium and vitamin D.
- Take at the same time every day.
- Take with or without food.
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 Tymlos Injection, solution 2000 ug/1mL Subcutaneous Radius Health, Inc. 2017-05-01 Not applicable US 
Categories
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Analogs/Derivatives
- Biological Factors
- Bone Density Conservation Agents
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Intercellular Signaling Peptides and Proteins
- Parathyroid Hormone-Related Protein
- Parathyroid Hormones and Analogues
- Peptide Hormones
- Peptides
- Proteins
- Thyroid Products
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- AVK0I6HY2U
- CAS number
- 247062-33-5
References
- General References
- Chew CK, Clarke BL: Abaloparatide: Recombinant human PTHrP (1-34) anabolic therapy for osteoporosis. Maturitas. 2017 Mar;97:53-60. doi: 10.1016/j.maturitas.2016.12.003. Epub 2016 Dec 15. [Article]
- Gonnelli S, Caffarelli C: Abaloparatide. Clin Cases Miner Bone Metab. 2016 May-Aug;13(2):106-109. Epub 2016 Oct 5. [Article]
- TYMLOS (abaloparatide) injection Label [Link]
- Radius Health, Inc. Pipeline [Link]
- External Links
- PubChem Substance
- 347909937
- ChemSpider
- 34443170
- 1921069
- ChEMBL
- CHEMBL4084894
- Wikipedia
- Abaloparatide
- FDA label
- Download (1.51 MB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Not Yet Recruiting Treatment Femoral Fractures 1 4 Recruiting Treatment Arthroplasties, Replacement, Knee / Osteoporosis 1 4 Recruiting Treatment Postmenopausal Osteoporosis 1 3 Active Not Recruiting Treatment Osteoporosis / Osteoporosis (Senile) / Osteoporosis Localized to Spine / Osteoporosis of Vertebrae / Osteoporosis, Age Related 1 3 Active Not Recruiting Treatment Postmenopausal Osteoporosis 1 3 Completed Treatment Osteoporosis / Osteoporosis (Senile) / Osteoporosis Localized to Spine / Osteoporosis of Vertebrae / Osteoporosis Risk / Osteoporosis Vertebral / Osteoporosis, Age Related / Osteoporotic Fractures / Postmenopausal Osteoporosis 1 3 Completed Treatment Osteoporosis / Postmenopausal Osteoporosis 1 2 Completed Treatment Osteoporosis 1 2 Completed Treatment Postmenopausal Osteoporosis 1 2 Not Yet Recruiting Treatment Odontoid Fracture 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Subcutaneous 2000 ug/1mL - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8148333 No 2012-04-03 2027-11-08 US US7803770 No 2010-09-28 2028-03-26 US US8748382 No 2014-06-10 2027-10-03 US US10996208 No 2018-04-30 2038-04-30 US
Properties
- State
- Liquid
- Experimental Properties
Property Value Source water solubility Soluble Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Ligand
- General Function
- Protein self-association
- Specific Function
- This is a receptor for parathyroid hormone and for parathyroid hormone-related peptide. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and also a phosphatid...
- Gene Name
- PTH1R
- Uniprot ID
- Q03431
- Uniprot Name
- Parathyroid hormone/parathyroid hormone-related peptide receptor
- Molecular Weight
- 66359.98 Da
References
- Jolette J, Attalla B, Varela A, Long GG, Mellal N, Trimm S, Smith SY, Ominsky MS, Hattersley G: Comparing the incidence of bone tumors in rats chronically exposed to the selective PTH type 1 receptor agonist abaloparatide or PTH(1-34). Regul Toxicol Pharmacol. 2017 Apr 4;86:356-365. doi: 10.1016/j.yrtph.2017.04.001. [Article]
- Hattersley G, Dean T, Corbin BA, Bahar H, Gardella TJ: Binding Selectivity of Abaloparatide for PTH-Type-1-Receptor Conformations and Effects on Downstream Signaling. Endocrinology. 2016 Jan;157(1):141-9. doi: 10.1210/en.2015-1726. Epub 2015 Nov 12. [Article]
Drug created on October 21, 2007 22:23 / Updated on April 30, 2021 13:06