Identification

Name
Alendronic acid
Accession Number
DB00630  (APRD00561)
Type
Small Molecule
Groups
Approved
Description

Alendronic acid (alendronate) is a nitrogen-containing, second generation bisphosphonate. Bisphosphonates were first used to treat Paget’s disease in 1971. This class of medications is comprised of inorganic pyrophosphate analogues that contain non-hydrolyzable P-C-P bonds. Similar to other bisphosphonates, alendronate has a high affinity for bone mineral and is taken up during osteoclast resorption. Alendronate inhibits farnesyl pyrophosphate synthetase, one of the enzymes in the mevalonic acid pathway involved in producing isoprenoid compounds that are essential for post-translational modification of small guanosine triphosphate (GTP)-binding proteins, such as Rho, Ras and Rab. Inhibition of this process interferes with osteoclast function and survival. Alendronate is used for the treatment of osteoporosis and Paget’s disease.

Structure
Thumb
Synonyms
  • (4-amino-1-hydroxybutane-1,1-diyl)bis(phosphonic acid)
  • (4-amino-1-hydroxybutylidene)bisphosphonic acid
  • 4-amino-1-hydroxybutane-1,1-diphosphonic acid
  • ABDP
  • Acide Alendronique
  • Acido Alendronico
  • Acidum Alendronicum
  • Alendronate
External IDs
G 704650 / GTH 4 / L 670 / L 670452 / MK 217
Product Ingredients
IngredientUNIICASInChI Key
Alendronate calcium3JTA994BVH137504-90-6VFAZUESUCBECNE-UHFFFAOYSA-L
Alendronate sodium2UY4M2U3RA121268-17-5DCSBSVSZJRSITC-UHFFFAOYSA-M
Alendronate sodium anhydrous4988K7X26P129318-43-0CAKRAHQRJGUPIG-UHFFFAOYSA-M
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act AlendronateTablet70 mgOralActavis Pharma Company2005-06-14Not applicableCanada
Act AlendronateTablet40 mgOralActavis Pharma Company2005-06-14Not applicableCanada
AlendronateTablet70 mgOralSanis Health Inc2010-07-30Not applicableCanada
AlendronateTablet70 mgOralCobalt LaboratoriesNot applicableNot applicableCanada
AlendronateTablet40 mgOralCobalt LaboratoriesNot applicableNot applicableCanada
AlendronateTablet70 mgOralSorres Pharma Inc2009-02-262014-06-20Canada
AlendronateTablet70 mgOralSivem Pharmaceuticals Ulc2008-03-13Not applicableCanada
Alendronate-70Tablet70 mgOralPro Doc Limitee2008-07-11Not applicableCanada
BinostoTablet, effervescent70 mg/1OralMission Pharmacal Company2012-09-03Not applicableUs
FosamaxSolution70 mg/75mLOralMerck & Co., Inc.2007-05-182007-05-18Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Accel-alendronateTablet70 mgOralAccel Pharma Inc2015-03-26Not applicableCanada
Accel-alendronateTablet10 mgOralAccel Pharma Inc2015-03-26Not applicableCanada
Accel-alendronateTablet5 mgOralAccel Pharma IncNot applicableNot applicableCanada
Ach-alendronateTablet70 mgOralAccord Healthcare Limited2012-03-20Not applicableCanada
Ach-alendronateTablet10 mgOralAccord Healthcare Limited2012-03-20Not applicableCanada
Ach-alendronateTablet5 mgOralAccord Healthcare Limited2012-03-20Not applicableCanada
AlendronateTablet70 mg/1OralA-S Medication Solutions2015-09-30Not applicableUs
AlendronateTablet35 mg/1OralHangzhou Minsheng Binjiang Pharmaceutical Co., Ltd.2017-12-05Not applicableUs
AlendronateTablet70 mg/1OralVirtus Pharmaceuticals2015-09-30Not applicableUs
AlendronateTablet70 mg/1OralNucare Pharmaceuticals,inc.2015-09-30Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
AdrovanceAlendronate sodium (70 mg) + Cholecalciferol (5600 IU)TabletOralMerck Sharp & Dohme B.V.2007-01-04Not applicableEu
AdrovanceAlendronate sodium (70 mg) + Cholecalciferol (2800 IU)TabletOralMerck Sharp & Dohme B.V.2007-01-04Not applicableEu
AdrovanceAlendronate sodium (70 mg) + Cholecalciferol (5600 IU)TabletOralMerck Sharp & Dohme B.V.2007-01-04Not applicableEu
AdrovanceAlendronate sodium (70 mg) + Cholecalciferol (2800 IU)TabletOralMerck Sharp & Dohme B.V.2007-01-04Not applicableEu
AdrovanceAlendronate sodium (70 mg) + Cholecalciferol (5600 IU)TabletOralMerck Sharp & Dohme B.V.2007-01-04Not applicableEu
AdrovanceAlendronate sodium (70 mg) + Cholecalciferol (2800 IU)TabletOralMerck Sharp & Dohme B.V.2007-01-04Not applicableEu
AdrovanceAlendronate sodium (70 mg) + Cholecalciferol (2800 IU)TabletOralMerck Sharp & Dohme B.V.2007-01-04Not applicableEu
Alendronate-cholecalciferolAlendronate sodium (70 mg) + Cholecalciferol (2800 unit)TabletOralFrosst A Division Of Merck Canada IncNot applicableNot applicableCanada
Alendronate-cholecalciferolAlendronate sodium (70 mg) + Cholecalciferol (5600 unit)TabletOralFrosst A Division Of Merck Canada IncNot applicableNot applicableCanada
Apo-alendronate/vitamin D3Alendronate sodium (70 mg) + Cholecalciferol (5600 unit)TabletOralApotex Corporation2016-07-21Not applicableCanada
International/Other Brands
Alenotop (Pliva) / Alned (Laboratorios Belmac) / Arendal (Ivax) / Beenos (Gedeon Richter) / Berlex (Duncan) / Denfos (Biofarma) / Densidron (Mepha) / Dronat (Farmavita) / Durost (Perumed) / Fixopan (Grupo Farma) / Forosa (Kemofarmacija) / Fosagen (Aspen Pharmacare) / Fosalen (Teriak) / Fosmin (Hospimedikka) / Fostolin (Actavis) / Fosval (Saval) / Huesobone (Farmaceutica Latina) / Lendrate (Actavis) / Oseolen (Intipharma) / Ostemax (Polpharma)
Categories
UNII
X1J18R4W8P
CAS number
66376-36-1
Weight
Average: 249.096
Monoisotopic: 249.016724799
Chemical Formula
C4H13NO7P2
InChI Key
OGSPWJRAVKPPFI-UHFFFAOYSA-N
InChI
InChI=1S/C4H13NO7P2/c5-3-1-2-4(6,13(7,8)9)14(10,11)12/h6H,1-3,5H2,(H2,7,8,9)(H2,10,11,12)
IUPAC Name
(4-amino-1-hydroxy-1-phosphonobutyl)phosphonic acid
SMILES
NCCCC(O)(P(O)(O)=O)P(O)(O)=O

Pharmacology

Indication

For the treatment and prevention of osteoporosis in women and Paget's disease of bone in both men and women.

Associated Conditions
Pharmacodynamics

Alendronate, a second-generation bisphosphonate is the first member of a group of drugs which strengthens bone. Alendronate is used to reduce hypercalcemia in tumor-induced bone disease, to treat corticosteroid-induced osteoporosis and Paget's disease, and to prevent osteoporosis in postmenopausal women.

Mechanism of action

The action of Alendronate on bone tissue is based partly on its affinity for hydroxyapatite, which is part of the mineral matrix of bone. Alendronate also targets farnesyl pyrophosphate (FPP) synthase. Nitrogen-containing bisphosphonates (such as pamidronate, alendronate, risedronate, ibandronate and zoledronate) appear to act as analogues of isoprenoid diphosphate lipids, thereby inhibiting FPP synthase, an enzyme in the mevalonate pathway. Inhibition of this enzyme in osteoclasts prevents the biosynthesis of isoprenoid lipids (FPP and GGPP) that are essential for the post-translational farnesylation and geranylgeranylation of small GTPase signalling proteins. This activity inhibits osteoclast activity and reduces bone resorption and turnover. In postmenopausal women, it reduces the elevated rate of bone turnover, leading to, on average, a net gain in bone mass.

TargetActionsOrganism
AFarnesyl pyrophosphate synthase
inhibitor
Human
AHydroxylapatite
antagonist
Human
UTyrosine-protein phosphatase non-receptor type 4
inhibitor
Human
UReceptor-type tyrosine-protein phosphatase S
inhibitor
Human
UReceptor-type tyrosine-protein phosphatase epsilon
inhibitor
Human
UV-type proton ATPase catalytic subunit A
inhibitor
Human
Absorption

Relative to an intravenous (IV) reference dose, the mean oral bioavailability of alendronate in women was 0.7% for doses ranging from 5 to 40 mg when administered after an overnight fast and two hours before a standardized breakfast. Oral bioavailability of the 10 mg tablet in men (0.59%) was similar to that in women (0.78%) when administered after an overnight fast and 2 hours before breakfast.

Volume of distribution
  • 28 L
Protein binding

78%

Metabolism

There is no evidence that alendronate is metabolized in humans or animals.

Route of elimination

Following a single IV dose of [14C]alendronate, approximately 50% of the radioactivity was excreted in the urine within 72 hours and little or no radioactivity was recovered in the feces.

Half life

>10 years

Clearance
  • <200 mL/min [A single 10 mg IV dose]
Toxicity

Alendronate can damage the esophagus both by toxicity from the medication itself and by nonspecific irritation secondary to contact between the pill and the esophageal mucosa, similar to other cases of "pill esophagitis."

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Alendronate Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AceclofenacThe risk or severity of gastrointestinal bleeding can be increased when Aceclofenac is combined with Alendronic acid.
AcemetacinThe risk or severity of gastrointestinal bleeding can be increased when Acemetacin is combined with Alendronic acid.
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Acetylsalicylic acid is combined with Alendronic acid.
AcipimoxThe risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Alendronic acid is combined with Acipimox.
AcyclovirThe risk or severity of nephrotoxicity and hypocalcemia can be increased when Acyclovir is combined with Alendronic acid.
AdefovirThe risk or severity of nephrotoxicity and hypocalcemia can be increased when Adefovir is combined with Alendronic acid.
Adefovir DipivoxilThe risk or severity of nephrotoxicity and hypocalcemia can be increased when Adefovir Dipivoxil is combined with Alendronic acid.
AlclofenacThe risk or severity of gastrointestinal bleeding can be increased when Alclofenac is combined with Alendronic acid.
AlmasilateThe serum concentration of Alendronic acid can be decreased when it is combined with Almasilate.
AlminoprofenThe risk or severity of gastrointestinal bleeding can be increased when Alminoprofen is combined with Alendronic acid.
Food Interactions
  • Take 30-60 minutes before breakfast.
  • Take with a full glass of water.

References

Synthesis Reference

Masahiko Dohi, Yuji Makino, Takao Hujii, "Sodium alendronate preparation for local administration." U.S. Patent US5958908, issued September, 1997.

US5958908
General References
  1. Russell RG, Watts NB, Ebetino FH, Rogers MJ: Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy. Osteoporos Int. 2008 Jun;19(6):733-59. doi: 10.1007/s00198-007-0540-8. [PubMed:18214569]
External Links
Human Metabolome Database
HMDB0001915
KEGG Compound
C07752
PubChem Compound
2088
PubChem Substance
46507199
ChemSpider
2004
BindingDB
25313
ChEBI
2567
ChEMBL
CHEMBL870
Therapeutic Targets Database
DAP000182
PharmGKB
PA448082
HET
212
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Alendronate
ATC Codes
M05BA04 — Alendronic acidM05BB05 — Alendronic acid, calcium and colecalciferol, sequentialM05BB03 — Alendronic acid and colecalciferolM05BB06 — Alendronic acid and alfacalcidol, sequential
AHFS Codes
  • 92:24.00 — Bone Resorption Inhibitors
PDB Entries
5dz2
FDA label
Download (105 KB)
MSDS
Download (24.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers3
1CompletedNot AvailableOsteopenia / Osteoporosis1
1CompletedPreventionViral Hepatitis B1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentOsteoporosis2
1RecruitingPreventionNeoplasms, Breast1
2Active Not RecruitingTreatmentCancer, Breast1
2Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2Active Not RecruitingTreatmentOsteoporosis1
2CompletedPreventionCancer of the Ovary1
2CompletedTreatmentBone Loss / Osteoporosis / Spinal Cord Injuries (SCI)1
2CompletedTreatmentGaucher's Disease / Osteopenia1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentLow Bone Mineral Density1
2CompletedTreatmentLow Bone Mineral Density / Postmenopausal Osteoporosis (PMO)1
2CompletedTreatmentOsteoporosis6
2CompletedTreatmentOsteoporosis / Postmenopausal Osteoporosis (PMO)1
2CompletedTreatmentPeriodontitis, Chronic1
2CompletedTreatmentPolyostotic Fibrous Dysplasia1
2CompletedTreatmentPostmenopausal Osteoporosis (PMO)2
2RecruitingTreatmentCalcific Aortic Stenosis1
2RecruitingTreatmentIOP / Osteoporosis1
2RecruitingTreatmentOsteoporosis / Rheumatoid Arthritis1
2SuspendedTreatmentHypogonadism / Osteopenia / Osteoporosis1
2TerminatedTreatmentAdenocarcinoma of the Prostate / Bone Metastases / Recurrent Prostate Cancer / Stage IV Prostate Cancer1
2TerminatedTreatmentOsteoporosis1
2, 3CompletedPreventionBone Resorption / Heart Transplantation / Transplantation, Liver1
2, 3CompletedTreatmentAsthma Bronchial1
2, 3CompletedTreatmentGlucocorticoid-Associated Osteopenia and Osteoporosis1
2, 3CompletedTreatmentPeriodontitis, Chronic3
2, 3RecruitingPreventionOsteoporosis, Steroid Induced1
2, 3Unknown StatusTreatmentOsteopenia / Osteoporosis1
3CompletedDiagnosticCancer, Breast / Osteoporosis1
3CompletedPreventionCancer, Breast1
3CompletedPreventionCardiac Transplantation / Osteoporosis1
3CompletedPreventionHypogonadism / Osteoporosis / Prostate Cancer1
3CompletedPreventionOsteopenia1
3CompletedTreatmentCystic Fibrosis (CF) / Osteoporosis1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Osteoporosis1
3CompletedTreatmentOsteopenia / Osteoporosis1
3CompletedTreatmentOsteoporosis6
3CompletedTreatmentPaget's Disease of Bone1
3CompletedTreatmentPostmenopausal Osteoporosis (PMO)3
3CompletedTreatmentPostmenopausal Women With Osteoporosis1
3CompletedTreatmentProstatic Neoplasms1
3TerminatedPreventionOsteoporosis1
3TerminatedTreatmentCerebral Palsy (CP) / Osteoporosis1
3TerminatedTreatmentOsteopenia / Osteoporosis1
3TerminatedTreatmentOsteoporosis1
3Unknown StatusPreventionOsteoporosis1
3Unknown StatusTreatmentOsteoporosis1
3WithdrawnTreatmentOsteoporosis / Postmenopausal Osteoporosis (PMO)1
4CompletedNot AvailableAnkylosing Spondylitis (AS) / Osteoporosis1
4CompletedPreventionArteriosclerosis / Calcifications, Vascular1
4CompletedPreventionCystic Fibrosis (CF) / Muscular Dystrophy / Osteoporosis1
4CompletedPreventionOsteopenia / Osteoporosis1
4CompletedTreatmentBone Diseases, Metabolic / Cystic Fibrosis (CF) / Osteoporosis1
4CompletedTreatmentCardiorenal Syndrome / Chronic Allograft Nephropathy (CAN)1
4CompletedTreatmentDepression / Healthy Volunteers / Osteopenia / Osteoporosis1
4CompletedTreatmentEnd-Stage Renal Disease (ESRD) / Osteoporosis1
4CompletedTreatmentIntrabony Periodontal Defect1
4CompletedTreatmentOsteogenesis Imperfecta1
4CompletedTreatmentOsteogenesis Imperfecta / Osteoporosis / Paget's Disease of Bone1
4CompletedTreatmentOsteoporosis5
4CompletedTreatmentOsteoporosis / Primary Hyperparathyroidism1
4CompletedTreatmentPostmenopausal Osteoporosis (PMO)4
4CompletedTreatmentRheumatoid Arthritis1
4Not Yet RecruitingTreatmentDepressive Syndrome1
4Not Yet RecruitingTreatmentOsteoporosis / Postmenopausal Osteoporosis (PMO)1
4RecruitingPreventionBone Demineralization1
4RecruitingTreatmentOsteoporosis1
4TerminatedTreatmentBack Pain1
4Unknown StatusPreventionNon-Traumatic Osteonecrosis1
4Unknown StatusTreatmentPeritoneal dialysis therapy1
4WithdrawnTreatmentHyperparathyroidism1
Not AvailableActive Not RecruitingNot AvailablePostmenopausal Osteoporosis (PMO) / Quality of Life / Vertebral Fractures1
Not AvailableActive Not RecruitingOtherLow Bone Density1
Not AvailableCompletedNot AvailableAdenocarcinomas / Esophageal Cancers / Squamous Cell Carcinoma (SCC)1
Not AvailableCompletedNot AvailableFracture Bone / Juvenile Osteoporosis / Low Bone Density1
Not AvailableCompletedNot AvailableOsteoporosis1
Not AvailableCompletedNot AvailablePerimenopausal Bone Loss1
Not AvailableCompletedNot AvailablePostmenopausal Osteoporosis (PMO)1
Not AvailableCompletedBasic SciencePrimary Hyperparathyroidism1
Not AvailableCompletedDiagnosticKidney (Renal Cell) Cancer / Neoplasms, Kidney / Renal Cell Adenocarcinoma1
Not AvailableCompletedTreatmentCystic Fibrosis (CF) / Osteoporosis1
Not AvailableCompletedTreatmentImpaired Renal Function1
Not AvailableCompletedTreatmentOsteopenia / Osteoporosis1
Not AvailableCompletedTreatmentOsteoporosis1
Not AvailableEnrolling by InvitationNot AvailableAtypical Femoral Fractures / Bisphosphonate Therapy / Osteoporosis1
Not AvailableNot Yet RecruitingNot AvailablePostmenopausal Osteoporosis (PMO)1
Not AvailableRecruitingTreatmentChronic Renal Failure (CRF)1
Not AvailableRecruitingTreatmentDifferentiated Thyroid Cancer (DTC) / Osteoporosis1
Not AvailableTerminatedNot AvailableOsteoporosis1
Not AvailableTerminatedPreventionOsteoporosis / Spinal Cord Injuries (SCI)1
Not AvailableUnknown StatusTreatmentArthroplasty, Replacement, Hip / Bone Density1

Pharmacoeconomics

Manufacturers
  • Merck and co inc
  • Apotex inc
  • Aurobindo pharma ltd
  • Austarpharma llc
  • Barr laboratories inc
  • Cadista pharmaceuticals inc
  • Dr reddys laboratories ltd
  • Genpharm ulc
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Sun pharma global inc
  • Teva pharmaceuticals usa
  • Watson laboratories
  • Watson laboratories inc
Packagers
  • Amerisource Health Services Corp.
  • Apotex Inc.
  • Arrow Pharm Malta Ltd.
  • A-S Medication Solutions LLC
  • Aurobindo Pharma Ltd.
  • Barr Pharmaceuticals
  • Cipla Ltd.
  • Cobalt Pharmaceuticals Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Doctor Reddys Laboratories Ltd.
  • Lake Erie Medical and Surgical Supply
  • Merck & Co.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Northstar Rx LLC
  • Nucare Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Rebel Distributors Corp.
  • Southwood Pharmaceuticals
  • Sun Pharmaceutical Industries Ltd.
  • Teva Pharmaceutical Industries Ltd.
  • UDL Laboratories
  • Watson Pharmaceuticals
Dosage forms
FormRouteStrength
SolutionOral70 mg/75mL
TabletOral10 mg/1
TabletOral40 mg/1
TabletOral70 mg/1
Tablet, effervescentOral70 mg/1
SolutionOral70 mg
TabletOral35 mg/1
TabletOral40 mg
TabletOral5 mg/1
TabletOral70 mg
Tablet, coatedOral10 mg/1
TabletOral10.0 mg
TabletOral5.0 mg
TabletOral70.0 mg
TabletOral10 mg
TabletOral5 mg
TabletOral
Prices
Unit descriptionCostUnit
Fosamax Plus D 4 70-2800 mg-Unit tablet Disp Pack107.66USD disp
Fosamax Plus D 4 70-5600 mg-Unit tablet Disp Pack107.66USD disp
Fosamax 1 Package = 4 tablet (70 mg) Package101.96USD package
Fosamax 1 Package = 4 tablet (35 mg) Package97.2USD package
Alendronate Sodium 4 35 mg tablet Package85.23USD package
Alendronate Sodium 4 70 mg tablet Package85.23USD package
Fosamax 70 mg/75ml Solution 75ml Bottle34.75USD bottle
Fosamax plus d 70 mg-5600 iu25.88USD each
Fosamax 70 mg tablet24.51USD tablet
Fosamax 35 mg tablet23.36USD tablet
Fosamax plus d 70 mg-2800 iu21.85USD each
Alendronate sodium 35 mg tablet20.49USD tablet
Alendronate sodium 70 mg tablet20.49USD tablet
Fosamax 40 mg tablet7.52USD tablet
Alendronate sodium 40 mg tablet6.73USD tablet
Fosamax 5 mg tablet3.4USD tablet
Fosamax 10 mg tablet3.4USD tablet
Alendronate sodium 10 mg tablet2.99USD tablet
Alendronate sodium 5 mg tablet2.99USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5358941No1992-12-022012-12-02Us
CA2190148No2006-02-142015-05-12Canada
CA2294595No2001-08-212018-07-17Canada
US5994329Yes1999-01-172019-01-17Us
US6015801Yes1999-01-172019-01-17Us
US6225294Yes1999-01-172019-01-17Us
US7964212No2003-03-062023-03-06Us
US7488496No2003-08-112023-08-11Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)234 dec °CPhysProp
water solubility1mg/LNot Available
logP-4.3Not Available
pKa2.72 (at 25 °C)MERCK INDEX (1996)
Predicted Properties
PropertyValueSource
Water Solubility16.9 mg/mLALOGPS
logP-1.3ALOGPS
logP-4.2ChemAxon
logS-1.2ALOGPS
pKa (Strongest Acidic)0.69ChemAxon
pKa (Strongest Basic)9.91ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area161.31 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity47.37 m3·mol-1ChemAxon
Polarizability19.4 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9554
Blood Brain Barrier+0.7065
Caco-2 permeable-0.7079
P-glycoprotein substrateNon-substrate0.6606
P-glycoprotein inhibitor INon-inhibitor0.947
P-glycoprotein inhibitor IINon-inhibitor0.9894
Renal organic cation transporterNon-inhibitor0.9205
CYP450 2C9 substrateNon-substrate0.8536
CYP450 2D6 substrateNon-substrate0.7997
CYP450 3A4 substrateNon-substrate0.6792
CYP450 1A2 substrateNon-inhibitor0.7567
CYP450 2C9 inhibitorNon-inhibitor0.9089
CYP450 2D6 inhibitorNon-inhibitor0.9344
CYP450 2C19 inhibitorNon-inhibitor0.9091
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9914
Ames testNon AMES toxic0.7079
CarcinogenicityNon-carcinogens0.7783
BiodegradationReady biodegradable0.6547
Rat acute toxicity1.6956 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8571
hERG inhibition (predictor II)Non-inhibitor0.8929
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
MS/MS Spectrum - Quattro_QQQ 10V, PositiveLC-MS/MSsplash10-014i-2930000000-99692afb4ed253251947
MS/MS Spectrum - Quattro_QQQ 25V, PositiveLC-MS/MSsplash10-001i-0900000000-d2c07307d66e1c7d52e8
MS/MS Spectrum - Quattro_QQQ 40V, PositiveLC-MS/MSsplash10-0kdl-9500000000-c82a6e6e898154627c7d
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as bisphosphonates. These are organic compounds containing two phosphonate groups linked together through a carbon atoms.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Organic phosphonic acids and derivatives
Sub Class
Bisphosphonates
Direct Parent
Bisphosphonates
Alternative Parents
Organic phosphonic acids / Organopnictogen compounds / Organophosphorus compounds / Organooxygen compounds / Organic oxides / Monoalkylamines / Hydrocarbon derivatives
Substituents
Bisphosphonate / Organophosphonic acid / Organic nitrogen compound / Organic oxygen compound / Organopnictogen compound / Organic oxide / Hydrocarbon derivative / Primary amine / Organophosphorus compound / Organooxygen compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
primary amino compound, 1,1-bis(phosphonic acid) (CHEBI:2567)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Poly(a) rna binding
Specific Function
Key enzyme in isoprenoid biosynthesis which catalyzes the formation of farnesyl diphosphate (FPP), a precursor for several classes of essential metabolites including sterols, dolichols, carotenoids...
Gene Name
FDPS
Uniprot ID
P14324
Uniprot Name
Farnesyl pyrophosphate synthase
Molecular Weight
48275.03 Da
References
  1. Bergstrom JD, Bostedor RG, Masarachia PJ, Reszka AA, Rodan G: Alendronate is a specific, nanomolar inhibitor of farnesyl diphosphate synthase. Arch Biochem Biophys. 2000 Jan 1;373(1):231-41. [PubMed:10620343]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  3. Dunford JE, Thompson K, Coxon FP, Luckman SP, Hahn FM, Poulter CD, Ebetino FH, Rogers MJ: Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J Pharmacol Exp Ther. 2001 Feb;296(2):235-42. [PubMed:11160603]
  4. Guo RT, Cao R, Liang PH, Ko TP, Chang TH, Hudock MP, Jeng WY, Chen CK, Zhang Y, Song Y, Kuo CJ, Yin F, Oldfield E, Wang AH: Bisphosphonates target multiple sites in both cis- and trans-prenyltransferases. Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10022-7. Epub 2007 May 29. [PubMed:17535895]
Kind
Small molecule
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
References
  1. Jahnke W, Henry C: An in vitro assay to measure targeted drug delivery to bone mineral. ChemMedChem. 2010 May 3;5(5):770-6. doi: 10.1002/cmdc.201000016. [PubMed:20209564]
  2. Nancollas GH, Tang R, Phipps RJ, Henneman Z, Gulde S, Wu W, Mangood A, Russell RG, Ebetino FH: Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone. 2006 May;38(5):617-27. Epub 2005 Jul 20. [PubMed:16046206]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Non-membrane spanning protein tyrosine phosphatase activity
Specific Function
May act at junctions between the membrane and the cytoskeleton.
Gene Name
PTPN4
Uniprot ID
P29074
Uniprot Name
Tyrosine-protein phosphatase non-receptor type 4
Molecular Weight
105910.315 Da
References
  1. Opas EE, Rutledge SJ, Golub E, Stern A, Zimolo Z, Rodan GA, Schmidt A: Alendronate inhibition of protein-tyrosine-phosphatase-meg1. Biochem Pharmacol. 1997 Sep 15;54(6):721-7. [PubMed:9310349]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine phosphatase activity
Specific Function
Interacts with LAR-interacting protein LIP.1.
Gene Name
PTPRS
Uniprot ID
Q13332
Uniprot Name
Receptor-type tyrosine-protein phosphatase S
Molecular Weight
217039.825 Da
References
  1. Opas EE, Rutledge SJ, Golub E, Stern A, Zimolo Z, Rodan GA, Schmidt A: Alendronate inhibition of protein-tyrosine-phosphatase-meg1. Biochem Pharmacol. 1997 Sep 15;54(6):721-7. [PubMed:9310349]
  2. Schmidt A, Rutledge SJ, Endo N, Opas EE, Tanaka H, Wesolowski G, Leu CT, Huang Z, Ramachandaran C, Rodan SB, Rodan GA: Protein-tyrosine phosphatase activity regulates osteoclast formation and function: inhibition by alendronate. Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):3068-73. [PubMed:8610169]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine phosphatase activity
Specific Function
Isoform 1 plays a critical role in signaling transduction pathways and phosphoprotein network topology in red blood cells. May play a role in osteoclast formation and function (By similarity).Isofo...
Gene Name
PTPRE
Uniprot ID
P23469
Uniprot Name
Receptor-type tyrosine-protein phosphatase epsilon
Molecular Weight
80641.165 Da
References
  1. Schmidt A, Rutledge SJ, Endo N, Opas EE, Tanaka H, Wesolowski G, Leu CT, Huang Z, Ramachandaran C, Rodan SB, Rodan GA: Protein-tyrosine phosphatase activity regulates osteoclast formation and function: inhibition by alendronate. Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):3068-73. [PubMed:8610169]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Proton-transporting atpase activity, rotational mechanism
Specific Function
Catalytic subunit of the peripheral V1 complex of vacuolar ATPase. V-ATPase vacuolar ATPase is responsible for acidifying a variety of intracellular compartments in eukaryotic cells.
Gene Name
ATP6V1A
Uniprot ID
P38606
Uniprot Name
V-type proton ATPase catalytic subunit A
Molecular Weight
68303.5 Da
References
  1. David P, Nguyen H, Barbier A, Baron R: The bisphosphonate tiludronate is a potent inhibitor of the osteoclast vacuolar H(+)-ATPase. J Bone Miner Res. 1996 Oct;11(10):1498-507. [PubMed:8889850]

Drug created on June 13, 2005 07:24 / Updated on November 14, 2018 12:44