MINODRONIC ACID

Details

Stereochemistry	ACHIRAL
Molecular Formula	C9H12N2O7P2
Molecular Weight	322.1483
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(CC1=CN=C2C=CC=CN12)(P(O)(O)=O)P(O)(O)=O

InChI

InChIKey=VMMKGHQPQIEGSQ-UHFFFAOYSA-N

InChI=1S/C9H12N2O7P2/c12-9(19(13,14)15,20(16,17)18)5-7-6-10-8-3-1-2-4-11(7)8/h1-4,6,12H,5H2,(H2,13,14,15)(H2,16,17,18)

HIDE SMILES / InChI

Description
Sources: https://dx.doi.org/10.1016%2Fs0065-7743%2810%2945028-9
Curator's Comment: description was created based on several sources, including https://www.astellas.com/en/corporate/news/pdf/110915_en_2.pdf | https://www.ncbi.nlm.nih.gov/pubmed/21110804

Minodronic acid (RECALBON®, Bonoteo®), a third-generation bisphosphonate, was approved in Japan for the oral treatment of osteoporosis. This drug increases the bone mineral density and the strength by inhibiting osteoclastic bone resorption. Nitrogen-containing bisphosphonates, such as minodronic acid (RECALBON®, Bonoteo®) induce osteoclast apoptosis by inhibiting farnesyl pyrophosphate synthase (FPPS), a key enzyme in the mevalonate pathway. Inhibition of FPPS in osteoclasts prevents the biosynthesis of isoprenoid lipids that are required for the prenylation of small GTPase signaling proteins necessary for osteoclast function. Similarly, nitrogen-containing bisphosphonates have been shown to inhibit farnesyl pyrophosphate/geranyl pyrophosphate synthase activity.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Geranylgeranyl pyrophosphate synthetase 18 Target ID: CHEMBL4769 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21110804	Inhibitor 8297	0.67 µM [IC50]
Farnesyl diphosphate synthase 28 Target ID: CHEMBL1782 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21110804	Inhibitor 8297	0.003 µM [IC50]
P2X2/P2X3 receptor 2 Target ID: CHEMBL3137277 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28243795	Antagonist 2778	62.7 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Osteoporosis 97 Sources: https://www.astellas.com/en/corporate/news/pdf/090121_eg.pdf	Primary		Approved 8429	BONOTEO Approved Use The drug was developed for the treatment of osteoporosis. Launch Date 2009

PubMed

Title	Date	PubMed
Nitrogen-containing bisphosphonate, YM529/ONO-5920 (a novel minodronic acid), inhibits RANKL expression in a cultured bone marrow stromal cell line ST2.	2005 Mar 4	15670755
[New development in bisphosphonate treatment. Review of the preventive effect of minodronic acid on fracture in Japanese patients with osteoporosis].	2009 Jan	19122267
[New development in bisphosphonate treatment. Review of effect on bone metabolism by minodronic acid in primary osteoporosis].	2009 Jan	19122266
Reduction of metastasis, cell invasion, and adhesion in mouse osteosarcoma by YM529/ONO-5920-induced blockade of the Ras/MEK/ERK and Ras/PI3K/Akt pathway.	2012 Mar 15	22326785

Patents

Sample Use Guides

In Vivo Use Guide

Normally in adults, 1 mg of minodronic acid (RECALBON®, Bonoteo®) is taken orally together with enough amount of water (180 ml) (or lukewarm water) once a day at the time of awakening. The drug must be taken without lying down at least for 30 minutes before the first food, beverage (other than plain water), and other oral medication.

Route of Administration: Oral

In Vitro Use Guide

The bone-binding characteristics of minodronic acid and morphological changes in rabbit osteoclasts were analyzed in vitro. In an osteoclast culture with 1 uM minodronic acid, 65% of minodronic acid was bound to bone, and C-terminal cross-linking telopeptide release was inhibited by 96%. Cultured osteoclasts without minodronic acid treatment formed ruffled borders and bone resorption lacunae and had rich cytoplasm, whereas those treated with 1 uM minodronic acid were not multinucleated, stained densely with toluidine blue, and were detached from the bone surface.

Name

Type

Language

MINODRONIC ACID

Official Name

English

MINODRONIC ACID [MI]

Common Name

English

MINODRONIC ACID [MART.]

Common Name

English

minodronic acid [INN]

Common Name

English

PHOSPHONIC ACID, (1-HYDROXY-2-IMIDAZO(1,2-A)PYRIDIN-3-YLETHYLIDENE)BIS-

Common Name

English

YM529

Code

English

Minodronic acid [WHO-DD]

Common Name

English

YM-529

Code

English

NSC-725590

Code

English

ONO-5920

Code

English

MINODRONATE

Common Name

English

(1-HYDROXY-2-IMIDAZO(1,2-A)PYRIDIN-3-YLETHYLIDENE)DIPHOSPHONIC ACID

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C67439