Page last updated: 2024-12-06

6-amino-1-hydroxyhexane-1,1-diphosphonate

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

6-amino-1-hydroxyhexane-1,1-diphosphonate: used for therapy of Paget's disease of bone & malignant hypercalcaemia [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID71237
CHEMBL ID55214
CHEBI ID135145
SCHEMBL ID87499
MeSH IDM0151249

Synonyms (52)

Synonym
neridronate, >=97% (nmr), solid
(6-amino-1-hydroxy-1-phosphono-hexyl)phosphonic acid
acide neridronique [inn-french]
acidum neridronicum [inn-latin]
6-amino-1-hydroxyhexane-1,1-diphosphonate
phosphonic acid, (6-amino-1-hydroxyhexylidene)bis-
neridronic acid [inn]
(6-amino-1-hydroxyhexylidene)diphosphonic acid
neridronic acid
acido neridronico [inn-spanish]
CHEBI:135145
79778-41-9
neridronate
ahhexbp
nerixia
CHEMBL55214 ,
(6-amino-1-hydroxy-1-phosphonohexyl)phosphonic acid
6-hydroxy-6,6-bis-phosphono-hexyl-ammonium
6-amino-1-hydroxyhexane-1,1-diyldiphosphonic acid
bdbm50098383
6-aminohexane-1-hydroxy-1,1-bisphosphonate
(6-amino-1-hydroxy-1-phosphono-hexyl)-phosphonic acid
acide neridronique
unii-8u27u3rin4
8u27u3rin4 ,
acido neridronico
acidum neridronicum
6-amino-1-hydroxyhexylidene bisphosphonic acid
FT-0630875
neridronic acid [mi]
neridronic acid [who-dd]
neridronic acid [mart.]
SCHEMBL87499
AKOS024462874
(6-amino-1-hydroxyhexane-1,1-diyl)diphosphonic acid
W-203821
mfcd00866995
nrd ,
(6-azanyl-1-oxidanyl-1-phosphono-hexyl)phosphonic acid
sr-01000945018
SR-01000945018-1
DB11620
BCP23891
HY-119443
79778-41-9 (free acid)
neridronate sodium hydrate
Q1651770
neridronic-acid
CS-0068386
A935873
(6-amino-1-hydroxyhexane-1,1-diyl)bis(phosphonic acid)
DTXSID40868545

Research Excerpts

Dosage Studied

ExcerptRelevanceReference
"5% of pretreatment values in the four groups, with a dose-response relationship that was apparent even between the two highest doses."( Short-term intravenous therapy with Neridronate in Paget's disease.
Adami, S; Bevilacqua, M; Braga, V; Broggini, M; Filipponi, P; Nannipieri, F; Ortolani, S; Palummeri, E; Ulivieri, F,
)
0.13
" The effect of intravenous infusions of bisphosphonates are, to a large extent, similar to equivalent intramuscular administrations, but doses and dosing intervals represent the critical issues."( Injectable bisphosphonates in the treatment of postmenopausal osteoporosis.
Adami, S; Crepaldi, G; Filipponi, P; Sartori, L, 2003
)
0.32
" A significant dose-response relationship over the three doses was observed for the BMD changes at the total hip but not at the spine."( Intramuscular neridronate in postmenopausal women with low bone mineral density.
Adami, S; Bertoldo, F; Costi, D; Di Munno, O; Filipponi, P; Fiore, CE; Frediani, B; Gatti, D; Marcocci, C; Palummeri, E; Rossini, M; Sartori, L, 2008
)
0.35
" All the patients were reviewed to determine duration, dosage and cumulative dose of their bisphosphonate therapy and were examined clinically to assess their oral health status."( Children and adolescents treated with neridronate for osteogenesis imperfecta show no evidence of any osteonecrosis of the jaw.
Antoniazzi, F; Cavarzere, P; Doro, F; Maines, E; Monti, E; Morandi, G, 2012
)
0.38
" infusion at the dosage of 2 mg/kg, up to a maximum of 100 mg at three-month intervals for 3 years."( Long-term Effects of Neridronate in Adults with Osteogenesis Imperfecta: An Observational Three-Year Italian Study.
Adami, G; Bertoldo, F; Fassio, A; Gatti, D; Idolazzi, L; Orsolini, G; Rossini, M; Viapiana, O, 2017
)
0.46
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
1,1-bis(phosphonic acid)Any member of the class of phosphonic acids in which a carbon atom is directly attached to two phosphonic acid groups. They are analogues of pyrophosphates (with the central oxygen atom replaced by a carbon atom) and like pyrophosphates they tend to have a strong affinity for bone, so are frequently used for their antiresorptive and hypocalcaemic properties.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (2)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Geranylgeranyl pyrophosphate synthaseHomo sapiens (human)IC50 (µMol)690.00000.00401.02764.5000AID74507
Farnesyl pyrophosphate synthaseHomo sapiens (human)IC50 (µMol)2.99650.00020.71099.3600AID318593; AID318594; AID72667; AID72669
Farnesyl pyrophosphate synthaseHomo sapiens (human)Ki0.30640.00010.21651.9000AID318593; AID318594; AID72668
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (6)

Processvia Protein(s)Taxonomy
isoprenoid metabolic processGeranylgeranyl pyrophosphate synthaseHomo sapiens (human)
geranyl diphosphate biosynthetic processGeranylgeranyl pyrophosphate synthaseHomo sapiens (human)
geranylgeranyl diphosphate biosynthetic processGeranylgeranyl pyrophosphate synthaseHomo sapiens (human)
farnesyl diphosphate biosynthetic processGeranylgeranyl pyrophosphate synthaseHomo sapiens (human)
isoprenoid biosynthetic processGeranylgeranyl pyrophosphate synthaseHomo sapiens (human)
cholesterol biosynthetic processFarnesyl pyrophosphate synthaseHomo sapiens (human)
geranyl diphosphate biosynthetic processFarnesyl pyrophosphate synthaseHomo sapiens (human)
farnesyl diphosphate biosynthetic processFarnesyl pyrophosphate synthaseHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (8)

Processvia Protein(s)Taxonomy
dimethylallyltranstransferase activityGeranylgeranyl pyrophosphate synthaseHomo sapiens (human)
farnesyltranstransferase activityGeranylgeranyl pyrophosphate synthaseHomo sapiens (human)
geranyltranstransferase activityGeranylgeranyl pyrophosphate synthaseHomo sapiens (human)
protein bindingGeranylgeranyl pyrophosphate synthaseHomo sapiens (human)
identical protein bindingGeranylgeranyl pyrophosphate synthaseHomo sapiens (human)
metal ion bindingGeranylgeranyl pyrophosphate synthaseHomo sapiens (human)
prenyltransferase activityGeranylgeranyl pyrophosphate synthaseHomo sapiens (human)
RNA bindingFarnesyl pyrophosphate synthaseHomo sapiens (human)
protein bindingFarnesyl pyrophosphate synthaseHomo sapiens (human)
metal ion bindingFarnesyl pyrophosphate synthaseHomo sapiens (human)
dimethylallyltranstransferase activityFarnesyl pyrophosphate synthaseHomo sapiens (human)
geranyltranstransferase activityFarnesyl pyrophosphate synthaseHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (5)

Processvia Protein(s)Taxonomy
nucleoplasmGeranylgeranyl pyrophosphate synthaseHomo sapiens (human)
cytoplasmGeranylgeranyl pyrophosphate synthaseHomo sapiens (human)
cytosolGeranylgeranyl pyrophosphate synthaseHomo sapiens (human)
Z discGeranylgeranyl pyrophosphate synthaseHomo sapiens (human)
perinuclear region of cytoplasmGeranylgeranyl pyrophosphate synthaseHomo sapiens (human)
nucleoplasmFarnesyl pyrophosphate synthaseHomo sapiens (human)
cytosolFarnesyl pyrophosphate synthaseHomo sapiens (human)
cytoplasmFarnesyl pyrophosphate synthaseHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (43)

Assay IDTitleYearJournalArticle
AID318593Inhibition of human recombinant FPPS expressed in Escherichia coli BL212008Journal of medicinal chemistry, Apr-10, Volume: 51, Issue:7
Structure-activity relationships among the nitrogen containing bisphosphonates in clinical use and other analogues: time-dependent inhibition of human farnesyl pyrophosphate synthase.
AID71580pIC50 value for stimulation of TNF-alpha release in gamma-delta T cells, using a constrained maximum TNF-alpha release of 2700 pg/mL2004Journal of medicinal chemistry, Jan-15, Volume: 47, Issue:2
Quantitative structure-activity relationships for gammadelta T cell activation by bisphosphonates.
AID660271Binding affinity to hydroxyapatite assessed as unadsorbed compound level at 20 mg after 3 hrs using 2.5 mg/ml of hydroxyapatite by NMR analysis relative to control2012European journal of medicinal chemistry, Jun, Volume: 52Synthesis, characterization and biological activity of hydroxyl-bisphosphonic analogs of bile acids.
AID660282Distribution coefficient, log D of the compound at pH 1.52012European journal of medicinal chemistry, Jun, Volume: 52Synthesis, characterization and biological activity of hydroxyl-bisphosphonic analogs of bile acids.
AID248772In vitro inhibitory concentration against the growth of Toxoplasma gondii in human foreskin fibroblast monolayer cells (HFF cells)2005Journal of medicinal chemistry, May-05, Volume: 48, Issue:9
Bisphosphonate inhibitors of Toxoplasma gondi growth: in vitro, QSAR, and in vivo investigations.
AID660273Binding affinity to hydroxyapatite assessed as unadsorbed compound level at 20 mg after 24 hrs using 2.5 mg/ml of hydroxyapatite by NMR analysis relative to control2012European journal of medicinal chemistry, Jun, Volume: 52Synthesis, characterization and biological activity of hydroxyl-bisphosphonic analogs of bile acids.
AID318595Inhibition of bone resorption in rat assessed as phosphate2008Journal of medicinal chemistry, Apr-10, Volume: 51, Issue:7
Structure-activity relationships among the nitrogen containing bisphosphonates in clinical use and other analogues: time-dependent inhibition of human farnesyl pyrophosphate synthase.
AID328054Inhibition of Escherichia coli F plasmid TraI relaxase Y16F mutant assessed as oriT ssDNA cleavage at 200 nM2007Proceedings of the National Academy of Sciences of the United States of America, Jul-24, Volume: 104, Issue:30
Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase.
AID72667Inhibitory activity against farnesyl Pyrophosphate Synthase was determined2003Journal of medicinal chemistry, Nov-20, Volume: 46, Issue:24
3-D QSAR investigations of the inhibition of Leishmania major farnesyl pyrophosphate synthase by bisphosphonates.
AID660275Binding affinity to hydroxyapatite assessed as unadsorbed compound level at 20 mg after 48 hrs using 5 mg/ml of hydroxyapatite by NMR analysis relative to control2012European journal of medicinal chemistry, Jun, Volume: 52Synthesis, characterization and biological activity of hydroxyl-bisphosphonic analogs of bile acids.
AID244679Therapeutic index (TI) value as ratio of lethal dose (LD50) to the inhibitory concentration (IC50)2005Journal of medicinal chemistry, May-05, Volume: 48, Issue:9
Bisphosphonate inhibitors of Toxoplasma gondi growth: in vitro, QSAR, and in vivo investigations.
AID208225Inhibition of Trypanosoma rhodesiense (strain STIB900) was determined using blood stream from trypomastigotes2001Journal of medicinal chemistry, Mar-15, Volume: 44, Issue:6
Bisphosphonates inhibit the growth of Trypanosoma brucei, Trypanosoma cruzi, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum: a potential route to chemotherapy.
AID660288Induction of apoptosis in human multinucleated osteoclasts obtained from PBMC assessed as formation of apoptotic nuclear bodies at 10'-5 M after 7 days by Hoechst 33258 staining2012European journal of medicinal chemistry, Jun, Volume: 52Synthesis, characterization and biological activity of hydroxyl-bisphosphonic analogs of bile acids.
AID74507Inhibitory activity against the human recombinant geranylgeranyl diphosphate synthase (GGPPSase).2002Journal of medicinal chemistry, May-23, Volume: 45, Issue:11
Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates and diphosphates: a potential route to new bone antiresorption and antiparasitic agents.
AID496819Antimicrobial activity against Plasmodium falciparum2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID318594Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins2008Journal of medicinal chemistry, Apr-10, Volume: 51, Issue:7
Structure-activity relationships among the nitrogen containing bisphosphonates in clinical use and other analogues: time-dependent inhibition of human farnesyl pyrophosphate synthase.
AID208084In vitro growth inhibition of bloodstream-form Trypanosoma brucei rhodesiense Trypomastigotes2002Journal of medicinal chemistry, Jul-04, Volume: 45, Issue:14
Activity of bisphosphonates against Trypanosoma brucei rhodesiense.
AID349070Inhibition of the ATP-mediated HIV1 reverse transcriptase D67N/K70R/T215F/K219Q mutant catalyzed 3'-azido, 3'-deoxythymidine excision from AZT-terminated DNA primers2008Bioorganic & medicinal chemistry, Oct-01, Volume: 16, Issue:19
Bisphosphonate inhibitors of ATP-mediated HIV-1 reverse transcriptase catalyzed excision of chain-terminating 3'-azido, 3'-deoxythymidine: a QSAR investigation.
AID660277Binding affinity to hydroxyapatite assessed as unadsorbed compound level at 20 mg after 72 hrs using 7.5 mg/ml of hydroxyapatite by NMR analysis relative to control2012European journal of medicinal chemistry, Jun, Volume: 52Synthesis, characterization and biological activity of hydroxyl-bisphosphonic analogs of bile acids.
AID210170Effective dose after subcutaneous administration to TPTX rats for 50% reduction of hypercalcemia2002Journal of medicinal chemistry, Aug-15, Volume: 45, Issue:17
Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa).
AID71581pIC50 value for stimulation of TNF-alpha release in gamma-delta T cells, using individual observed maximum TNF-alpha release2004Journal of medicinal chemistry, Jan-15, Volume: 47, Issue:2
Quantitative structure-activity relationships for gammadelta T cell activation by bisphosphonates.
AID214469Inhibition of Trypanosoma cruzi Amastigotes was determined in Vero cells culture and fetal calf serum2001Journal of medicinal chemistry, Mar-15, Volume: 44, Issue:6
Bisphosphonates inhibit the growth of Trypanosoma brucei, Trypanosoma cruzi, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum: a potential route to chemotherapy.
AID158550In vitro growth inhibition against Plasmodium falciparum2004Journal of medicinal chemistry, Jan-01, Volume: 47, Issue:1
Effects of bisphosphonates on the growth of Entamoeba histolytica and Plasmodium species in vitro and in vivo.
AID328053Inhibition of Escherichia coli F plasmid TraI relaxase Y16F mutant assessed as oriT ssDNA cleavage at 200 nM2007Proceedings of the National Academy of Sciences of the United States of America, Jul-24, Volume: 104, Issue:30
Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase.
AID660281Distribution coefficient, log D of the compound at pH 7.42012European journal of medicinal chemistry, Jun, Volume: 52Synthesis, characterization and biological activity of hydroxyl-bisphosphonic analogs of bile acids.
AID72668Binding affinity towards farnesyl Pyrophosphate Synthase using [14C]- isopentenyl pyrophosphate as radioligand2003Journal of medicinal chemistry, Nov-20, Volume: 46, Issue:24
3-D QSAR investigations of the inhibition of Leishmania major farnesyl pyrophosphate synthase by bisphosphonates.
AID1852260Inhibition of Bacillus cereus collagenase unit of N-terminal His6-tagged ColQ1 expressed in Escherichia coli NiCo21(DE3) cells at 100 uM incubated for 144 seconds by FRET based assay relative to control2022Journal of medicinal chemistry, 10-13, Volume: 65, Issue:19
Discovery and Characterization of Synthesized and FDA-Approved Inhibitors of Clostridial and Bacillary Collagenases.
AID235219Therapeutic index measured as the ratio of LD50 (KB cells) to IC50 (T.b. rhodesiense)2002Journal of medicinal chemistry, Jul-04, Volume: 45, Issue:14
Activity of bisphosphonates against Trypanosoma brucei rhodesiense.
AID96034Toxicity evaluated against human nasopharyngeal carcinoma KB cell line2004Journal of medicinal chemistry, Jan-01, Volume: 47, Issue:1
Effects of bisphosphonates on the growth of Entamoeba histolytica and Plasmodium species in vitro and in vivo.
AID95764Inhibition of L. donovani (Amastigotes) strain MHOM/ET/67/L82 maintained in female golden hamsters2001Journal of medicinal chemistry, Mar-15, Volume: 44, Issue:6
Bisphosphonates inhibit the growth of Trypanosoma brucei, Trypanosoma cruzi, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum: a potential route to chemotherapy.
AID71579Inhibitory activity, for stimulation of TNF-alpha release in gamma-delta T cells, using individual observed maximum TNF-alpha release2004Journal of medicinal chemistry, Jan-15, Volume: 47, Issue:2
Quantitative structure-activity relationships for gammadelta T cell activation by bisphosphonates.
AID151353Inhibition of Plasmodium falciparum 3D7 in erythrocytes2001Journal of medicinal chemistry, Mar-15, Volume: 44, Issue:6
Bisphosphonates inhibit the growth of Trypanosoma brucei, Trypanosoma cruzi, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum: a potential route to chemotherapy.
AID67525In vitro growth inhibition against Entamoeba histolytica2004Journal of medicinal chemistry, Jan-01, Volume: 47, Issue:1
Effects of bisphosphonates on the growth of Entamoeba histolytica and Plasmodium species in vitro and in vivo.
AID72669Inhibitory activity against farnesyl Pyrophosphate Synthase expressed as #NAME? (M)2003Journal of medicinal chemistry, Nov-20, Volume: 46, Issue:24
3-D QSAR investigations of the inhibition of Leishmania major farnesyl pyrophosphate synthase by bisphosphonates.
AID71578Inhibitory activity, for stimulation of TNF-alpha release in gamma-delta T cells, using a constrained maximum TNF-alpha release of 2700 pg/mL2004Journal of medicinal chemistry, Jan-15, Volume: 47, Issue:2
Quantitative structure-activity relationships for gammadelta T cell activation by bisphosphonates.
AID496826Antimicrobial activity against Entamoeba histolytica2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID249161Lethal dose required to inhibit the growth of human KB (nasopharyngeal carcinoma) cell line2005Journal of medicinal chemistry, May-05, Volume: 48, Issue:9
Bisphosphonate inhibitors of Toxoplasma gondi growth: in vitro, QSAR, and in vivo investigations.
AID660284Cytotoxicity against mouse L929 cells assessed as cell viability after 72 hrs by neutral-red uptake assay2012European journal of medicinal chemistry, Jun, Volume: 52Synthesis, characterization and biological activity of hydroxyl-bisphosphonic analogs of bile acids.
AID275054Antibacterial activity against Escherichia coli W31102006Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25
Isoprenoid biosynthesis as a drug target: bisphosphonate inhibition of Escherichia coli K12 growth and synergistic effects of fosmidomycin.
AID9382850% lethal dose for inhibition of KB cells growth2002Journal of medicinal chemistry, Jul-04, Volume: 45, Issue:14
Activity of bisphosphonates against Trypanosoma brucei rhodesiense.
AID660286Inhibition of osteoclastogenesis in human osteoclasts obtained from PBMC assessed as formation of TRAPC positive multinucleated cells at 10'-5 to 10'-9 M after 7 days2012European journal of medicinal chemistry, Jun, Volume: 52Synthesis, characterization and biological activity of hydroxyl-bisphosphonic analogs of bile acids.
AID208218Log IC50 brucei Trypomastigotes2002Journal of medicinal chemistry, Jul-04, Volume: 45, Issue:14
Activity of bisphosphonates against Trypanosoma brucei rhodesiense.
AID660279Binding affinity to hydroxyapatite assessed as unadsorbed compound level at 20 mg after 96 hrs using 10 mg/ml of hydroxyapatite by NMR analysis relative to control2012European journal of medicinal chemistry, Jun, Volume: 52Synthesis, characterization and biological activity of hydroxyl-bisphosphonic analogs of bile acids.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (91)

TimeframeStudies, This Drug (%)All Drugs %
pre-19902 (2.20)18.7374
1990's5 (5.49)18.2507
2000's42 (46.15)29.6817
2010's32 (35.16)24.3611
2020's10 (10.99)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 10.56

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be weak demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index10.56 (24.57)
Research Supply Index4.85 (2.92)
Research Growth Index5.42 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (10.56)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials27 (27.00%)5.53%
Reviews7 (7.00%)6.00%
Case Studies15 (15.00%)4.05%
Observational2 (2.00%)0.25%
Other49 (49.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]