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Details

Stereochemistry ACHIRAL
Molecular Formula C9H12N2O7P2
Molecular Weight 322.1487
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MINODRONIC ACID

SMILES

c1ccn2c(CC(O)(P(=O)(O)O)P(=O)(O)O)cnc2c1

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
Curator's Comment:: 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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.67000000000000004 µM [IC50]
0.00300000000000000006 µM [IC50]
62.7000000000000028 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
BONOTEO

Approved Use

The drug was developed for the treatment of osteoporosis.

Launch Date

1232409600000
PubMed

PubMed

TitleDatePubMed
Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates.
2001 Feb
Stabilization of minodronic acid in aqueous solution for parenteral formulation.
2001 Jul 3
Failure of stability prediction for minodronic acid injectable by accelerated stability testing.
2002 Jul 8
A new stressed test to predict the foreign matter formation of minodronic acid in solution.
2003 Jan 30
Effect of minodronic acid (ONO-5920) on bone mineral density and arthritis in adult rats with collagen-induced arthritis.
2003 Jun
Effects of YM529, a novel minodronic acid, on adjuvant arthritis in rats.
2004 Jan-Feb
A third-generation bisphosphonate, minodronic acid (YM529), augments the interferon alpha/beta-mediated inhibition of renal cell cancer cell growth both in vitro and in vivo.
2005 Jan 15
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
The effect of bisphosphonates on gene expression: GAPDH as a housekeeping or a new target gene?
2006 Mar 3
A third-generation bisphosphonate, minodronic acid (YM529), successfully prevented the growth of bladder cancer in vitro and in vivo.
2006 Nov 20
Minodronic acid influences receptor activator of nuclear factor kappaB ligand expression and suppresses bone resorption by osteoclasts in rats with collagen-induced arthritis.
2007
Anti-tumor effect of bisphosphonate (YM529) on non-small cell lung cancer cell lines.
2007 Jan 12
Combined effects of a third-generation bisphosphonate, zoledronic acid with other anticancer agents against murine osteosarcoma.
2007 Jan 29
[New bone density conservation agents for osteoporosis under research and development: Minodronic acid].
2007 Nov 28
Minodronic acid, a third-generation bisphosphonate, antagonizes purinergic P2X(2/3) receptor function and exerts an analgesic effect in pain models.
2008 Jul 28
Efficacy of a nitrogen-containing bisphosphonate, minodronate, in conjunction with a p38 mitogen activated protein kinase inhibitor or doxorubicin against malignant bone tumor cells.
2008 Jun
Minodronic acid (ONO-5920/YM529) prevents decrease in bone mineral density and bone strength, and improves bone microarchitecture in ovariectomized cynomolgus monkeys.
2008 Nov
Long-term minodronic acid (ONO-5920/YM529) treatment suppresses increased bone turnover, plus prevents reduction in bone mass and bone strength in ovariectomized rats with established osteopenia.
2008 Nov
Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates: a crystallographic and computational investigation.
2008 Sep 25
[New development in bisphosphonate treatment. Review of the preventive effect of minodronic acid on fracture in Japanese patients with osteoporosis].
2009 Jan
[New development in bisphosphonate treatment. Review of effect on bone metabolism by minodronic acid in primary osteoporosis].
2009 Jan
Anti-tumour activity of bisphosphonates in preclinical models of breast cancer.
2010
Synthesis, chiral high performance liquid chromatographic resolution and enantiospecific activity of a potent new geranylgeranyl transferase inhibitor, 2-hydroxy-3-imidazo[1,2-a]pyridin-3-yl-2-phosphonopropionic acid.
2010 May 13
Expression of Msx-1 is suppressed in bisphosphonate associated osteonecrosis related jaw tissue-etiopathology considerations respecting jaw developmental biology-related unique features.
2010 Oct 13
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
Patents

Sample Use Guides

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
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
INN   MART.   MI   WHO-DD  
INN  
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
YM 529
Code English
YM-529
Code English
NSC-725590
Code English
ONO-5920
Code English
MINODRONIC ACID [WHO-DD]
Common Name 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
Created by admin on Fri Jun 25 21:58:18 UTC 2021 , Edited by admin on Fri Jun 25 21:58:18 UTC 2021
Code System Code Type Description
ChEMBL
CHEMBL319144
Created by admin on Fri Jun 25 21:58:18 UTC 2021 , Edited by admin on Fri Jun 25 21:58:18 UTC 2021
PRIMARY
EPA CompTox
180064-38-4
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PRIMARY
DRUG BANK
DB06548
Created by admin on Fri Jun 25 21:58:18 UTC 2021 , Edited by admin on Fri Jun 25 21:58:18 UTC 2021
PRIMARY
CAS
180064-38-4
Created by admin on Fri Jun 25 21:58:18 UTC 2021 , Edited by admin on Fri Jun 25 21:58:18 UTC 2021
PRIMARY
NCI_THESAURUS
C81673
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PRIMARY
INN
7651
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PRIMARY
EVMPD
SUB08981MIG
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PRIMARY
DRUG CENTRAL
4074
Created by admin on Fri Jun 25 21:58:18 UTC 2021 , Edited by admin on Fri Jun 25 21:58:18 UTC 2021
PRIMARY
FDA UNII
40SGR63TGL
Created by admin on Fri Jun 25 21:58:18 UTC 2021 , Edited by admin on Fri Jun 25 21:58:18 UTC 2021
PRIMARY
MESH
C087958
Created by admin on Fri Jun 25 21:58:18 UTC 2021 , Edited by admin on Fri Jun 25 21:58:18 UTC 2021
PRIMARY
PUBCHEM
130956
Created by admin on Fri Jun 25 21:58:18 UTC 2021 , Edited by admin on Fri Jun 25 21:58:18 UTC 2021
PRIMARY
MERCK INDEX
M7554
Created by admin on Fri Jun 25 21:58:18 UTC 2021 , Edited by admin on Fri Jun 25 21:58:18 UTC 2021
PRIMARY Merck Index
WIKIPEDIA
MINODRONIC ACID
Created by admin on Fri Jun 25 21:58:18 UTC 2021 , Edited by admin on Fri Jun 25 21:58:18 UTC 2021
PRIMARY