Alendronic acid (T3D2666)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (7)XML
Targets (7)
Record Information
Version2.0
Creation Date2009-07-15 20:43:20 UTC
Update Date2014-12-24 20:25:48 UTC
Accession NumberT3D2666
Identification
Common NameAlendronic acid
ClassSmall Molecule
DescriptionAlendronate 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.
Compound Type
  • Amine
  • Antihypocalcemic Agent
  • Antiresorptive
  • Bisphosphonate
  • Bone Density Conservation Agent
  • Drug
  • Food Toxin
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
Synonym
(4-Amino-1-hydroxybutylidene)bisphosphonic acid
Acide Alendronique
Acido Alendronico
Acidum Alendronicum
Alendronate
Alendronate Sodium
Alendronate sodium hydrate
Alenotop
Alned
Arendal
Beenos
Berlex
Binosto
Denfos
Densidron
Dronat
Durost
Fixopan
Forosa
Fosagen
Fosalen
Fosamax
Fosmin
Fostolin
Fosval
Huesobone
Lendrate
Oseolen
Ostemax
Chemical FormulaC4H13NO7P2
Average Molecular Mass249.096 g/mol
Monoisotopic Mass249.017 g/mol
CAS Registry Number66376-36-1
IUPAC Name(4-amino-1-hydroxy-1-phosphonobutyl)phosphonic acid
Traditional Namealendronate
SMILESNCCCC(O)(P(O)(O)=O)P(O)(O)=O
InChI IdentifierInChI=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)
InChI KeyInChIKey=OGSPWJRAVKPPFI-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as bisphosphonates. These are organic compounds containing two phosphonate groups linked together through a carbon atoms.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassOrganic phosphonic acids and derivatives
Sub ClassBisphosphonates
Direct ParentBisphosphonates
Alternative Parents
Substituents
  • Bisphosphonate
  • Organophosphonic acid
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Primary amine
  • Organophosphorus compound
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Amine
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Intestine
  • Prostate
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point234 dec°C
Boiling PointNot Available
Solubility1mg/L
LogP-4.3
Predicted Properties
PropertyValueSource
Water Solubility16.9 g/LALOGPS
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 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity47.37 m³·mol⁻¹ChemAxon
Polarizability19.4 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-001i-9010000000-6b540b3cfe12455ee0472017-08-28View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-001i-9020000000-f4a0f6418448b21083712017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-014i-2930000000-99692afb4ed2532519472012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-001i-0900000000-d2c07307d66e1c7d52e82012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0kdl-9500000000-c82a6e6e898154627c7d2012-07-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0ue9-0590000000-ed1b4585584330309b422017-07-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0uyi-4900000000-42101c55bda7e112b2af2017-07-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-001i-9330000000-8ac66f69531027a0950f2017-07-25View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00kb-2590000000-2c9bde6c398541c5cb712017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-017i-6950000000-d1f8822b01485883083d2017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-003r-9000000000-7b5e5c1f9b218640040b2017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-0090000000-0b08500c08babf97a7352021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-005a-9050000000-04116055e92ba5f8a66f2021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-03gi-9000000000-8274f2b488ab919859ff2021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0090000000-eb3a6c3bae79932540c82021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udi-0190000000-7b88a34c07f93b4e47792021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-9100000000-12b406fbd4d8f99b2d4d2021-09-23View Spectrum
1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
Toxicity Profile
Route of ExposureRelative 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.
Mechanism of ToxicityThe 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.
MetabolismThere 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
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment and prevention of osteoporosis in women and Paget's disease of bone in both men and women.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsAlendronate 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."
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00630
HMDB IDHMDB01915
PubChem Compound ID2088
ChEMBL IDCHEMBL870
ChemSpider ID2004
KEGG IDC07752
UniProt IDNot Available
OMIM ID125700 , 145000
ChEBI ID2567
BioCyc IDALENDRONATE
CTD IDNot Available
Stitch IDAlendronic acid
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkAlendronate
References
Synthesis Reference

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

MSDSLink
General References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. 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. [18214569 ]
  3. Virtanen SS, Vaananen HK, Harkonen PL, Lakkakorpi PT: Alendronate inhibits invasion of PC-3 prostate cancer cells by affecting the mevalonate pathway. Cancer Res. 2002 May 1;62(9):2708-14. [11980672 ]
  4. Ezra A, Hoffman A, Breuer E, Alferiev IS, Monkkonen J, El Hanany-Rozen N, Weiss G, Stepensky D, Gati I, Cohen H, Tormalehto S, Amidon GL, Golomb G: A peptide prodrug approach for improving bisphosphonate oral absorption. J Med Chem. 2000 Oct 5;43(20):3641-52. [11020278 ]
  5. Cremers SC, van Hogezand R, Banffer D, den Hartigh J, Vermeij P, Papapoulos SE, Hamdy NA: Absorption of the oral bisphosphonate alendronate in osteoporotic patients with Crohn's disease. Osteoporos Int. 2005 Dec;16(12):1727-30. Epub 2005 Jun 15. [15959617 ]
  6. Sarno M, Sarno L, Baylink D, Drinkwater B, Farley S, Kleerekoper M, Lang R, Lappe J, Licata A, McClung M, Miller P, Nattrass S, Recker R, Schwartz EN, Tucci JR, Wolf S, Powell H, Tjersland G, Warnick GR: Excretion of sweat and urine pyridinoline crosslinks in healthy controls and subjects with established metabolic bone disease. Clin Chem Lab Med. 2001 Mar;39(3):223-8. [11350019 ]
  7. Rossini M, Gatti D, Isaia G, Sartori L, Braga V, Adami S: Effects of oral alendronate in elderly patients with osteoporosis and mild primary hyperparathyroidism. J Bone Miner Res. 2001 Jan;16(1):113-9. [11149474 ]
  8. Makowski GS, Ramsby ML: Autoactivation profiles of calcium-dependent matrix metalloproteinase-2 and -9 in inflammatory synovial fluid: effect of pyrophosphate and bisphosphonates. Clin Chim Acta. 2005 Aug;358(1-2):182-91. [15921672 ]
  9. Yalcin F, Gurgan S, Gurgan T: The effect of menopause, hormone replacement therapy (HRT), alendronate (ALN), and calcium supplements on saliva. J Contemp Dent Pract. 2005 May 15;6(2):10-7. [15915200 ]
  10. Rudge S, Hailwood S, Horne A, Lucas J, Wu F, Cundy T: Effects of once-weekly oral alendronate on bone in children on glucocorticoid treatment. Rheumatology (Oxford). 2005 Jun;44(6):813-8. Epub 2005 Feb 3. [15695300 ]
  11. Ravn P, Thompson DE, Ross PD, Christiansen C: Biochemical markers for prediction of 4-year response in bone mass during bisphosphonate treatment for prevention of postmenopausal osteoporosis. Bone. 2003 Jul;33(1):150-8. [12919710 ]
  12. Chesnut CH 3rd, Harris ST: Short-term effect of alendronate on bone mass and bone remodeling in postmenopausal women. Osteoporos Int. 1993;3 Suppl 3:S17-9. [8298198 ]
  13. Yun MH, Kwon KI: High-performance liquid chromatography method for determining alendronate sodium in human plasma by detecting fluorescence: application to a pharmacokinetic study in humans. J Pharm Biomed Anal. 2006 Jan 23;40(1):168-72. Epub 2005 Aug 10. [16095861 ]
  14. Drugs.com [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

Target Details
1. Farnesyl pyrophosphate synthase
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, and ubiquinones. FPP also serves as substrate for protein farnesylation and geranylgeranylation. Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate product farnesyl pyrophosphate.
Gene Name:
FDPS
Uniprot ID:
P14324
Molecular Weight:
48275.03 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.0442 uMNot AvailableBindingDB 25313
Inhibitory0.3931 uMNot AvailableBindingDB 25313
IC500.05 uMNot AvailableBindingDB 25313
IC500.26 uMNot AvailableBindingDB 25313
IC500.95 uMNot AvailableBindingDB 25313
IC500.955 uMNot AvailableBindingDB 25313
IC502.249 uMNot AvailableBindingDB 25313
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. 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. [10620343 ]
  3. 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. [17535895 ]
  4. Szabo CM, Matsumura Y, Fukura S, Martin MB, Sanders JM, Sengupta S, Cieslak JA, Loftus TC, Lea CR, Lee HJ, Koohang A, Coates RM, Sagami H, Oldfield E: Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates and diphosphates: a potential route to new bone antiresorption and antiparasitic agents. J Med Chem. 2002 May 23;45(11):2185-96. [12014956 ]
  5. Mucha A, Kafarski P, Berlicki L: Remarkable potential of the alpha-aminophosphonate/phosphinate structural motif in medicinal chemistry. J Med Chem. 2011 Sep 8;54(17):5955-80. doi: 10.1021/jm200587f. Epub 2011 Aug 5. [21780776 ]
  6. Dunford JE, Kwaasi AA, Rogers MJ, Barnett BL, Ebetino FH, Russell RG, Oppermann U, Kavanagh KL: Structure-activity relationships among the nitrogen containing bisphosphonates in clinical use and other analogues: time-dependent inhibition of human farnesyl pyrophosphate synthase. J Med Chem. 2008 Apr 10;51(7):2187-95. doi: 10.1021/jm7015733. Epub 2008 Mar 8. [18327899 ]
  7. Sanders JM, Gomez AO, Mao J, Meints GA, Van Brussel EM, Burzynska A, Kafarski P, Gonzalez-Pacanowska D, Oldfield E: 3-D QSAR investigations of the inhibition of Leishmania major farnesyl pyrophosphate synthase by bisphosphonates. J Med Chem. 2003 Nov 20;46(24):5171-83. [14613320 ]
Target Details
2. Receptor-type tyrosine-protein phosphatase S
General Function:
Transmembrane receptor protein tyrosine phosphatase activity
Specific Function:
Interacts with LAR-interacting protein LIP.1.
Gene Name:
PTPRS
Uniprot ID:
Q13332
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. [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. [8610169 ]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
Target Details
3. Geranylgeranyl pyrophosphate synthase
General Function:
Metal ion binding
Specific Function:
Catalyzes the trans-addition of the three molecules of IPP onto DMAPP to form geranylgeranyl pyrophosphate, an important precursor of carotenoids and geranylated proteins.
Gene Name:
GGPS1
Uniprot ID:
O95749
Molecular Weight:
34870.625 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50436.52 uMNot AvailableBindingDB 25313
IC50440 uMNot AvailableBindingDB 25313
References
  1. K-M Chen C, Hudock MP, Zhang Y, Guo RT, Cao R, No JH, Liang PH, Ko TP, Chang TH, Chang SC, Song Y, Axelson J, Kumar A, Wang AH, Oldfield E: Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates: a crystallographic and computational investigation. J Med Chem. 2008 Sep 25;51(18):5594-607. doi: 10.1021/jm800325y. [18800762 ]
  2. Szabo CM, Matsumura Y, Fukura S, Martin MB, Sanders JM, Sengupta S, Cieslak JA, Loftus TC, Lea CR, Lee HJ, Koohang A, Coates RM, Sagami H, Oldfield E: Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates and diphosphates: a potential route to new bone antiresorption and antiparasitic agents. J Med Chem. 2002 May 23;45(11):2185-96. [12014956 ]
Target Details
4. Hydroxylapatite
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. [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. [16046206 ]
Target Details
5. Receptor-type tyrosine-protein phosphatase epsilon
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).Isoform 2 acts as a negative regulator of insulin receptor (IR) signaling in skeletal muscle. Regulates insulin-induced tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate 1 (IRS-1), phosphorylation of protein kinase B and glycogen synthase kinase-3 and insulin induced stimulation of glucose uptake (By similarity).Isoform 1 and isoform 2 act as a negative regulator of FceRI-mediated signal transduction leading to cytokine production and degranulation, most likely by acting at the level of SYK to affect downstream events such as phosphorylation of SLP76 and LAT and mobilization of Ca(2+).
Gene Name:
PTPRE
Uniprot ID:
P23469
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. [8610169 ]
Target Details
6. Tyrosine-protein phosphatase non-receptor type 4
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
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. [9310349 ]
Target Details
7. V-type proton ATPase catalytic subunit A
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
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. [8889850 ]