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
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)
| Molecular Formula | C9H12N2O7P2 |
| Molecular Weight | 322.1483 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionCurator'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
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
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL4769 |
0.67 µM [IC50] | ||
Target ID: CHEMBL1782 |
0.003 µM [IC50] | ||
Target ID: CHEMBL3137277 |
62.7 µM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | BONOTEO Approved UseThe drug was developed for the treatment of osteoporosis. Launch Date1.23240959E12 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| 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 |
|
| 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.
| Substance Class |
Chemical
Created
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40SGR63TGL
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C67439
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MINODRONIC ACID
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