MINODRONIC ACID MONOHYDRATE

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C9H12N2O7P2.H2O
Molecular Weight	340.1636
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of MINODRONIC ACID MONOHYDRATE

SMILES

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

InChI

InChIKey=GPAPAOGRNKUFGH-UHFFFAOYSA-N

InChI=1S/C9H12N2O7P2.H2O/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);1H2

HIDE SMILES / InChI

Molecular Formula	H2O
Molecular Weight	18.0153
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C9H12N2O7P2
Molecular Weight	322.1483
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description

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	Inhibitor 8,504	0.67 µM [IC50]
Farnesyl diphosphate synthase 28	Inhibitor 8,504	0.003 µM [IC50]
P2X2/P2X3 receptor 2	Antagonist 2,849	62.7 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Osteoporosis 101	Primary		Approved 8,583	BONOTEO

C_max

Value	Dose	Analyte	Population
0.3895 ng/mL	1 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
0.1913 ng/mL	1 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
1.405 ng/mL	4 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
0.638 ng/mL	4 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
0.216 ng/mL	4 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
0.072 ng/mL	0.1 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
0.017 ng/mL	0.2 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
0.119 ng/mL	0.5 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
0.189 ng/mL	1 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
0.726 ng/mL	2 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
0.665 ng/mL	4 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
2.431 ng/mL	8 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
0.874 ng/mL	4 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
2.85 ng/mL	8 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
2.333 ng/mL	12 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
0.3134 ng/mL	1 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
0.2564 ng/mL	1 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
0.5555 ng/mL	1 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
0.6512 ng/mL	1 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
0.676 ng/mL	2 mg 1 times / day multiple, oral	MINODRONIC ACID plasma	Homo sapiens
0.93 ng/mL	2 mg 1 times / day multiple, oral	MINODRONIC ACID plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
1.549 ng × h/mL	1 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
0.445 ng × h/mL	1 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
4.12 ng × h/mL	4 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
1.41 ng × h/mL	4 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
0.7 ng × h/mL	4 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
0.04 ng × h/mL	0.1 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
0.01 ng × h/mL	0.2 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
0.19 ng × h/mL	0.5 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
0.37 ng × h/mL	1 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
2.15 ng × h/mL	2 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
2.26 ng × h/mL	4 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
9.28 ng × h/mL	8 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
3.52 ng × h/mL	4 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
10.98 ng × h/mL	8 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
10.16 ng × h/mL	12 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
1.325 ng × h/mL	1 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
1.074 ng × h/mL	1 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
2.814 ng × h/mL	1 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
3.051 ng × h/mL	1 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
1.92 ng × h/mL	2 mg 1 times / day multiple, oral	MINODRONIC ACID plasma	Homo sapiens
3.24 ng × h/mL	2 mg 1 times / day multiple, oral	MINODRONIC ACID plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
9.7 h	1 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
6.6 h	1 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
1.3 h	4 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
1.4 h	4 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
1.7 h	4 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
2.3 h	4 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
4.7 h	8 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
4.4 h	12 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
8.2 h	1 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
11.5 h	1 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
9.7 h	1 mg single, oral	MINODRONIC ACID plasma	Homo sapiens
9.9 h	1 mg single, oral	MINODRONIC ACID plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
38.1%			MINODRONIC ACID plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
56 mg single, oral Higher than recommended	unhealthy, ADULT	Other AEs: Acute kidney injury...
4 mg single, oral Highest studied dose	healthy, ADULT
6 mg 1 times / day multiple, oral Highest studied dose	unhealthy, ADULT	Other AEs: Osteonecrosis of jaw...

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AEs

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AE	Significance	Dose	Population
Acute kidney injury		56 mg single, oral Higher than recommended	unhealthy, ADULT
Osteonecrosis of jaw		6 mg 1 times / day multiple, oral Highest studied dose	unhealthy, ADULT

Showing 1 to 2 of 2 entries

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PubMed

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Title	Date	PubMed
[New bone density conservation agents for osteoporosis under research and development: Minodronic acid].	2007 Nov 28	18161142
Minodronic acid, a third-generation bisphosphonate, antagonizes purinergic P2X(2/3) receptor function and exerts an analgesic effect in pain models.	2008 Jul 28	18565509
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	18687415
Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates: a crystallographic and computational investigation.	2008 Sep 25	18800762
Anti-tumour activity of bisphosphonates in preclinical models of breast cancer.	2010	21176176

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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.

Substance Class	Chemical
Record UNII	457X74V7ND
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

MINODRONIC ACID HYDRATE

Preferred Name

English

MINODRONIC ACID MONOHYDRATE

Common Name

English

PHOSPHONIC ACID, P,P'-(1-HYDROXY-2-IMIDAZO(1,2-A)PYRIDIN-3-YLETHYLIDENE)BIS-, HYDRATE (1:1)

Common Name

English

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

Common Name

English

MINODRONIC ACID MONOHYDRATE [MI]

Common Name

English

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Code System

Code

Type

Description

SMS_ID

100000125990

PRIMARY

PUBCHEM

23201029

PRIMARY

EPA CompTox

DTXSID80165944

PRIMARY

FDA UNII

457X74V7ND

PRIMARY

CAS

155648-60-5

PRIMARY

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SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound