In preclinical animal studies:Abaloparatide HELPED BUILD BONE1
Abaloparatide, a PTHrP(1-34) analog1:
In animal models of postmenopausal osteoporosis, abaloparatide maintained or improved bone quality at all skeletal sites evaluated and did not cause any mineralization defects1
*Bone microarchitecture can be understood in terms of trabecular architecture (thickness, orientation, spacing of the trabeculae, and the extent to which the trabeculae are interconnected) and cortical thickness and integrity.2
Abaloparatide is a PTHrP(1-34) analog1
Differences in the amino acid sequence of abaloparatide and hPTHrP(1-34) are indicated by highlighted circles.
In addition, abaloparatide is 41% homologous to hPTH(1-34)1
Specifically designed to build bone
Abaloparatide demonstrated 1600-fold-greater selectivity to the receptor conformation that drivesbone formation (RG) than to the receptor conformation that drives bone resorption (R0)6
Arrow thickness is illustrative only and not drawn to scale.
Thickness of arrows is a figurative representation of the levels of binding selectivity between the RG conformation and the R0 conformation of the PTH1 receptor for abaloparatide, PTHrP, and PTH.
Data based on an in vitro study examining the binding of ABL (abaloparatide), PTH(1-34), PTHrP(1-36), and LA-PTH (long-acting PTH)to 2 distinct PTHR1 conformations (RG and R0) as well as the associated cAMP signaling and duration of response.6
See how TYMLOS stimulatedbone turnover markers
References: 1. TYMLOS® [prescribing information]. Waltham, MA: Radius Health, Inc; 2017. 2. Felsenberg D, Boonen S. The bone quality framework: determinants of bone strength and their interrelationships, and implications for osteoporosis management. Clin Ther. 2005;27(1):1-11. 3. IUPAC-IUB Commission on Biochemical Nomenclature (CBN). A one-letter notation for amino acid sequences. Eur J Biochem. 1968;5:151-153. 4. Pioszak AA, Parker NR, Gardella TJ, Xu HE. Structural basis for parathyroid hormone-related protein binding to the parathyroid hormone receptor and design of conformation-selective peptides. J Biol Chem. 2009;284(41):28382-28391. 5. National Center for Biotechnology Information. Parathyroid hormone-like hormone [Homo sapiens]. https://www.ncbi.nlm.nih.gov/protein/AAH05961.1. Accessed July 3, 2017. 6. 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;157(1):141-149.