Abstract

Introduction: Bisphosphonates (BPs) are widely used to manage a variety of bone disorders, including osteoporosis, metastatic bone disease and myeloma bone disease. The nitrogen-containing BPs (NBPs) target osteoclast activity by disrupting protein prenylation via inhibition of farnesyl diphosphate synthase (FDPS). Areas covered: This review summarizes the recent advances in BPs with a focus on the latest patents (2015–2018). Patents involving novel BPs, new modes of BP delivery, as well as use of BPs to deliver other drugs to bone are discussed. A review of phosphonate-based drugs targeting geranylgeranyl diphosphate synthase (GGDPS) or geranylgeranyl transferase II (GGTase II) as alternative strategies to disrupt protein geranylgeranylation is provided. Expert opinion: While the NBPs remain the mainstay of treatment for most bone disorders, further understanding of their pharmacological properties could lead to further refinement of their chemical structures and optimization of efficacy and safety profiles. In addition, the development of NBP analogs or drug delivery mechanisms that allow for nonbone tissue exposure could allow for the use of these drugs as direct anticancer agents. The development of GGDPS and GGTase II inhibitors represents alternative heterocycle phosphonate-based strategies to disrupt protein geranylgeranylation and may have potential as anticancer agents and/or as bone-targeted therapies.

Original languageEnglish (US)
Pages (from-to)315-325
Number of pages11
JournalExpert Opinion on Therapeutic Patents
Volume29
Issue number5
DOIs
StatePublished - May 4 2019

Fingerprint

Bone Diseases
Diphosphonates
Protein Prenylation
Farnesyltranstransferase
Bone and Bones
Organophosphonates
Nitrogen
Patents
Antineoplastic Agents
Geranyltranstransferase
Pharmaceutical Preparations
Expert Testimony
Osteoclasts
Drug Delivery Systems
Osteoporosis
Pharmacology
Safety
Therapeutics

Keywords

  • Bisphosphonate
  • farnesyl diphosphate synthase
  • lytic bone disease
  • osteoporosis

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Cite this

A patent review of bisphosphonates in treating bone disease. / Holstein, Sarah A.

In: Expert Opinion on Therapeutic Patents, Vol. 29, No. 5, 04.05.2019, p. 315-325.

Research output: Contribution to journalArticle

@article{ce48bf9a2a4b4b7c8201feeb2de68e09,
title = "A patent review of bisphosphonates in treating bone disease",
abstract = "Introduction: Bisphosphonates (BPs) are widely used to manage a variety of bone disorders, including osteoporosis, metastatic bone disease and myeloma bone disease. The nitrogen-containing BPs (NBPs) target osteoclast activity by disrupting protein prenylation via inhibition of farnesyl diphosphate synthase (FDPS). Areas covered: This review summarizes the recent advances in BPs with a focus on the latest patents (2015–2018). Patents involving novel BPs, new modes of BP delivery, as well as use of BPs to deliver other drugs to bone are discussed. A review of phosphonate-based drugs targeting geranylgeranyl diphosphate synthase (GGDPS) or geranylgeranyl transferase II (GGTase II) as alternative strategies to disrupt protein geranylgeranylation is provided. Expert opinion: While the NBPs remain the mainstay of treatment for most bone disorders, further understanding of their pharmacological properties could lead to further refinement of their chemical structures and optimization of efficacy and safety profiles. In addition, the development of NBP analogs or drug delivery mechanisms that allow for nonbone tissue exposure could allow for the use of these drugs as direct anticancer agents. The development of GGDPS and GGTase II inhibitors represents alternative heterocycle phosphonate-based strategies to disrupt protein geranylgeranylation and may have potential as anticancer agents and/or as bone-targeted therapies.",
keywords = "Bisphosphonate, farnesyl diphosphate synthase, lytic bone disease, osteoporosis",
author = "Holstein, {Sarah A.}",
year = "2019",
month = "5",
day = "4",
doi = "10.1080/13543776.2019.1608180",
language = "English (US)",
volume = "29",
pages = "315--325",
journal = "Expert Opinion on Therapeutic Patents",
issn = "1354-3776",
publisher = "Informa Healthcare",
number = "5",

}

TY - JOUR

T1 - A patent review of bisphosphonates in treating bone disease

AU - Holstein, Sarah A.

PY - 2019/5/4

Y1 - 2019/5/4

N2 - Introduction: Bisphosphonates (BPs) are widely used to manage a variety of bone disorders, including osteoporosis, metastatic bone disease and myeloma bone disease. The nitrogen-containing BPs (NBPs) target osteoclast activity by disrupting protein prenylation via inhibition of farnesyl diphosphate synthase (FDPS). Areas covered: This review summarizes the recent advances in BPs with a focus on the latest patents (2015–2018). Patents involving novel BPs, new modes of BP delivery, as well as use of BPs to deliver other drugs to bone are discussed. A review of phosphonate-based drugs targeting geranylgeranyl diphosphate synthase (GGDPS) or geranylgeranyl transferase II (GGTase II) as alternative strategies to disrupt protein geranylgeranylation is provided. Expert opinion: While the NBPs remain the mainstay of treatment for most bone disorders, further understanding of their pharmacological properties could lead to further refinement of their chemical structures and optimization of efficacy and safety profiles. In addition, the development of NBP analogs or drug delivery mechanisms that allow for nonbone tissue exposure could allow for the use of these drugs as direct anticancer agents. The development of GGDPS and GGTase II inhibitors represents alternative heterocycle phosphonate-based strategies to disrupt protein geranylgeranylation and may have potential as anticancer agents and/or as bone-targeted therapies.

AB - Introduction: Bisphosphonates (BPs) are widely used to manage a variety of bone disorders, including osteoporosis, metastatic bone disease and myeloma bone disease. The nitrogen-containing BPs (NBPs) target osteoclast activity by disrupting protein prenylation via inhibition of farnesyl diphosphate synthase (FDPS). Areas covered: This review summarizes the recent advances in BPs with a focus on the latest patents (2015–2018). Patents involving novel BPs, new modes of BP delivery, as well as use of BPs to deliver other drugs to bone are discussed. A review of phosphonate-based drugs targeting geranylgeranyl diphosphate synthase (GGDPS) or geranylgeranyl transferase II (GGTase II) as alternative strategies to disrupt protein geranylgeranylation is provided. Expert opinion: While the NBPs remain the mainstay of treatment for most bone disorders, further understanding of their pharmacological properties could lead to further refinement of their chemical structures and optimization of efficacy and safety profiles. In addition, the development of NBP analogs or drug delivery mechanisms that allow for nonbone tissue exposure could allow for the use of these drugs as direct anticancer agents. The development of GGDPS and GGTase II inhibitors represents alternative heterocycle phosphonate-based strategies to disrupt protein geranylgeranylation and may have potential as anticancer agents and/or as bone-targeted therapies.

KW - Bisphosphonate

KW - farnesyl diphosphate synthase

KW - lytic bone disease

KW - osteoporosis

UR - http://www.scopus.com/inward/record.url?scp=85064839029&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064839029&partnerID=8YFLogxK

U2 - 10.1080/13543776.2019.1608180

DO - 10.1080/13543776.2019.1608180

M3 - Article

C2 - 31023104

AN - SCOPUS:85064839029

VL - 29

SP - 315

EP - 325

JO - Expert Opinion on Therapeutic Patents

JF - Expert Opinion on Therapeutic Patents

SN - 1354-3776

IS - 5

ER -