Pamidronic acid

Identification

Summary

Pamidronic acid is a bisphosphonate used to treat Paget's disease, to treat hypercalcemia of malignancy, and to treat osteolytic bone lesions.

Brand Names
Pamisol
Generic Name
Pamidronic acid
DrugBank Accession Number
DB00282
Background

Pamidronic acid is a second generation, nitrogen containing bisphosphonate similar to neridronic acid and alendronic acid.2 Pamidronic acid was first described in the literature in 1977.9 The second generation bisphosphonates are less common as third generation bisphosphonates, such as ibandronic acid, zoledronic acid, minodronic acid, and risedronic acid are becoming more popular.2

Pamidronic acid was granted FDA approval on 31 October 1991.10

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 235.0695
Monoisotopic: 235.001074735
Chemical Formula
C3H11NO7P2
Synonyms
  • Acide pamidronique
  • Acido pamidronico
  • Acidum pamidronicum
  • Pamidronate
  • Pamidronic acid

Pharmacology

Indication

Pamidronate is indicated to treat moderate to severe hypercalcemia of malignancy, moderate to severe Paget's disease of bone, osteolytic bone metastases of breast cancer, and osteolytic lesions of multiple myeloma.11

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofHypercalcemia of malignancy•••••••••••••••••••••
Treatment ofOsteolytic lesion•••••••••••••••••••••
Treatment ofPaget's disease•••••••••••••••••••••
Treatment ofOsteolytic bone metastases•••••••••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Pamidronic acid is a second generation, nitrogen containing bisphosphonate that inhibits osteoclast mediated bone loss2,3,11 It has a wide therapeutic index and a long duration of action as it can be given every 3-4 weeks for certain indications.11 Patients should be counselled regarding the risk of elevated blood urea nitrogen, renal tubular necrosis, and nephrotoxicity.11

Mechanism of action

Bisphosphonates are taken into the bone where they bind to hydroxyapatite. Bone resorption by osteoclasts causes local acidification, releasing the bisphosphonate, which is taken into the osteoclast by fluid-phase endocytosis.3 Endocytic vesicles become acidified, releasing bisphosphonates into the cytosol of osteoclasts where they act.3

Osteoclasts mediate resorption of bone.4 When osteoclasts bind to bone they form podosomes, ring structures of F-actin.4 Disruption of the podosomes causes osteoclasts to detach from bones, preventing bone resorption.4

Nitrogen containing bisphosphonates such as pamidronate are known to induce apoptosis of hematopoietic tumor cells by inhibiting the components of the mevalonate pathway farnesyl diphosphate synthase, farnesyl diphosphate, and geranylgeranyl diphosphate.5,6,2 These components are essential for post-translational prenylation of GTP-binding proteins like Rap1.5,6 The lack of prenylation of these proteins interferes with their function, and in the case of Rap1, leads to apoptosis.5,6 pamidronate also activated caspases 3 and 9 which further contribute to apoptosis.5,6,7

TargetActionsOrganism
AFarnesyl pyrophosphate synthase
inhibitor
Humans
AHydroxylapatite
antagonist
Humans
UGeranylgeranyl pyrophosphate synthase
inhibitor
Humans
UCaspase-3
activator
Humans
UCaspase-9
activator
Humans
Absorption

In patients with a creatinine clearance >90mL/min, a 90mg intravenous dose reached a Cmax of 1.92±1.08µg/mL, with a Tmax of 4h, and an AUC of 10.2±6.95µg*h/mL.8

In patients with a creatinine clearance 61-90mL/min, a 90mg intravenous dose reached a Cmax of 1.86±0.50µg/mL, with a Tmax of 4h, and an AUC of 10.7—3.91µg*h/mL.[A203264

In patients with a creatinine clearance 30-60mL/min, a 90mg intravenous dose reached a Cmax of 1.84±0.58µg/mL, with a Tmax of 4h, and an AUC of 10.1±3.38µg*h/mL.8

In patients with a creatinine clearance <30mL/min, a 90mg intravenous dose reached a Cmax of 1.93±0.53µg/mL, with a Tmax of 4h, and an AUC of 34.0±8.37µg*h/mL.8

Volume of distribution

Not Available

Protein binding

Pamidronate is approximately 54% protein bound in serum.12

Metabolism

Pamidronate is not metabolized in vivo.11

Route of elimination

Pamidronate is exclusively eliminated in the urine.11 By 120 hours after administration, 46±16% of the dose has been eliminated in the urine.11

Half-life

The mean elimination half life of pamidronate is 28±7 hours.11

Clearance

The mean total clearance of pamidronate is 107±50mL/min and the mean renal clearance is 49±28mL/min.11

Adverse Effects
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Toxicity

Patients experiencing and overdose may present with hypocalcemia, fever, hypotension, and taste perversion.11 Overdose can be managed by symptomatic and supportive treatment which may include the administration of steroids and intravenous calcium.11

Pathways
PathwayCategory
Pamidronate Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirPamidronic acid may decrease the excretion rate of Abacavir which could result in a higher serum level.
AceclofenacThe risk or severity of gastrointestinal bleeding can be increased when Aceclofenac is combined with Pamidronic acid.
AcemetacinThe risk or severity of gastrointestinal bleeding can be increased when Acemetacin is combined with Pamidronic acid.
AcetaminophenPamidronic acid may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
Acetylsalicylic acidThe risk or severity of gastrointestinal bleeding can be increased when Acetylsalicylic acid is combined with Pamidronic acid.
Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Pamidronate DisodiumC7S8VWP5DH109552-15-0CEYUIFJWVHOCPP-UHFFFAOYSA-L
International/Other Brands
Aminomux / Pamimed / Ribodroat
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ArediaPowder, for solution60 mg / vialIntravenousNovartis1994-12-312001-07-30Canada flag
ArediaInjection, powder, lyophilized, for solution90 mg/10mLIntravenousNovartis1991-10-032011-09-30US flag
ArediaInjection, powder, lyophilized, for solution30 mg/10mLIntravenousNovartis1991-10-312012-02-29US flag
Aredia 30mgPowder, for solution30 mg / vialIntravenousNovartis1994-12-312016-02-23Canada flag
Aredia 90mgPowder, for solution90 mg / vialIntravenousNovartis1994-12-312016-02-23Canada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Pamidronate DisodiumInjection, powder, lyophilized, for solution3 mg/1mLIntravenousAreva Pharmaceuticals Inc.2013-08-06Not applicableUS flag
Pamidronate DisodiumInjection, solution9 mg/1mLIntravenousHospira Worldwide, Inc.2011-06-232011-06-23US flag
Pamidronate DisodiumSolution9 mg/1mLIntravenousBarr Laboratories2008-09-112012-05-22US flag
Pamidronate DisodiumInjection, solution3 mg/1mLIntravenousHospira, Inc.2005-10-01Not applicableUS flag
Pamidronate DisodiumInjection, solution3 mg/1mLIntravenousPfizer Laboratories Div Pfizer Inc.2011-05-102017-12-31US flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
AREDIA 90 MG/10 ML FLAKON, 1 ADETPamidronic acid (90 mg/10ml)SolutionIntravenousNOVARTİS ÜRÜNLERİ2018-02-202022-04-11Turkey flag
PAMIDRIA 90 MG/10 ML IV INFUZYON ICIN KONSANTRE COZELTI ICEREN FLAKON, 1 ADETPamidronic acid (90 mg/10ml)Injection, solution, concentrateIntravenousPHARMADA İLAÇ SAN. VE TİC. A.Ş.2018-02-202024-01-23Turkey flag
PAMIDRONAT DISODYUM DBL 90 MG/10 ML FLAKON, 1 ADETPamidronate Disodium (90 mg/10ml)SolutionIntravenousORNA İLAÇ TEKSTİL KİMYEVİ MAD. SAN. VE DIŞ TİC. LTD. ŞTİ.2019-04-30Not applicableTurkey flag

Categories

ATC Codes
M05BA03 — Pamidronic acid
Drug Categories
Chemical TaxonomyProvided by Classyfire
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 / 1,3-aminoalcohols / Organopnictogen compounds / Organophosphorus compounds / Organooxygen compounds / Organic oxides / Monoalkylamines / Hydrocarbon derivatives
Substituents
1,3-aminoalcohol / Aliphatic acyclic compound / Amine / Bisphosphonate / Hydrocarbon derivative / Organic nitrogen compound / Organic oxide / Organic oxygen compound / Organonitrogen compound / Organooxygen compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
OYY3447OMC
CAS number
40391-99-9
InChI Key
WRUUGTRCQOWXEG-UHFFFAOYSA-N
InChI
InChI=1S/C3H11NO7P2/c4-2-1-3(5,12(6,7)8)13(9,10)11/h5H,1-2,4H2,(H2,6,7,8)(H2,9,10,11)
IUPAC Name
(3-amino-1-hydroxy-1-phosphonopropyl)phosphonic acid
SMILES
NCCC(O)(P(O)(O)=O)P(O)(O)=O

References

Synthesis Reference

Edward C. Shinal, "Method for preparation of disodium pamidronate." U.S. Patent US6268524, issued February, 1988.

US6268524
General References
  1. Zarychanski R, Elphee E, Walton P, Johnston J: Osteonecrosis of the jaw associated with pamidronate therapy. Am J Hematol. 2006 Jan;81(1):73-5. [Article]
  2. Cremers S, Drake MT, Ebetino FH, Bilezikian JP, Russell RGG: Pharmacology of bisphosphonates. Br J Clin Pharmacol. 2019 Jun;85(6):1052-1062. doi: 10.1111/bcp.13867. Epub 2019 Feb 28. [Article]
  3. 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. [Article]
  4. Murakami H, Takahashi N, Tanaka S, Nakamura I, Udagawa N, Nakajo S, Nakaya K, Abe M, Yuda Y, Konno F, Barbier A, Suda T: Tiludronate inhibits protein tyrosine phosphatase activity in osteoclasts. Bone. 1997 May;20(5):399-404. [Article]
  5. Miwa A, Takezako N, Hayakawa H, Hayakawa M, Tominaga S, Yanagisawa K: YM-175 induces apoptosis of human native monocyte-lineage cells via inhibition of prenylation. Am J Hematol. 2012 Dec;87(12):1084-8. doi: 10.1002/ajh.23328. Epub 2012 Oct 9. [Article]
  6. Ullen A, Schwarz S, Lennartsson L, Kalkner KM, Sandstrom P, Costa F, Lennernas B, Linder S, Nilsson S: Zoledronic acid induces caspase-dependent apoptosis in renal cancer cell lines. Scand J Urol Nephrol. 2009;43(2):98-103. doi: 10.1080/00365590802475904. [Article]
  7. Wada A, Fukui K, Sawai Y, Imanaka K, Kiso S, Tamura S, Shimomura I, Hayashi N: Pamidronate induced anti-proliferative, apoptotic, and anti-migratory effects in hepatocellular carcinoma. J Hepatol. 2006 Jan;44(1):142-50. doi: 10.1016/j.jhep.2005.09.022. Epub 2005 Nov 9. [Article]
  8. Berenson JR, Rosen L, Vescio R, Lau HS, Woo M, Sioufi A, Kowalski MO, Knight RD, Seaman JJ: Pharmacokinetics of pamidronate disodium in patients with cancer with normal or impaired renal function. J Clin Pharmacol. 1997 Apr;37(4):285-90. doi: 10.1002/j.1552-4604.1997.tb04304.x. [Article]
  9. Bijvoet OL, Reitsma PH, Frijlink WB: Bisphosphonates and Paget's disease. Lancet. 1980 Jun 28;1(8183):1416-7. doi: 10.1016/s0140-6736(80)92679-3. [Article]
  10. FDA Approved Drug Products: Aredia Pamidronate Intravenous Injection (Discontinued) [Link]
  11. FDA Approved Drug Products: Aredia Pamidronate Intravenous Injection [Link]
  12. Pfizer Canada: Pamidronate Disodium Injection [Link]
Human Metabolome Database
HMDB0014427
KEGG Drug
D07281
KEGG Compound
C07395
PubChem Compound
4674
PubChem Substance
46504823
ChemSpider
4512
BindingDB
12581
RxNav
11473
ChEBI
7903
ChEMBL
CHEMBL834
ZINC
ZINC000003812862
Therapeutic Targets Database
DAP001416
PharmGKB
PA450767
PDBe Ligand
210
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Pamidronic_acid
PDB Entries
2f89 / 3sdr / 4kpj / 4nkf / 4ogu / 5erm / 5ero / 7kj8 / 8su1
FDA label
Download (59.5 KB)
MSDS
Download (49.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedOtherBreast Cancer / Metastatic Cancer1
4CompletedTreatmentBone Loss1
4CompletedTreatmentBreast Cancer1
4CompletedTreatmentBreast Cancer / Metastatic Cancer / Prostate Cancer1
4CompletedTreatmentComplications of Heart-lung Transplant / Osteopenia (Disorder) / Other Complications of Lung Transplant1

Pharmacoeconomics

Manufacturers
  • Novartis pharmaceuticals corp
  • Aesgen inc
  • Akorn strides llc
  • App pharmaceuticals llc
  • Bedford laboratories div ben venue laboratories inc
  • Cipla ltd
  • Generamedix inc
  • Hospira inc
  • Mn pharmaceuticals
  • Pharmaforce inc
  • Pliva lachema as
  • Sun pharma global inc
  • Teva parenteral medicines inc
Packagers
  • Akorn Inc.
  • American Regent
  • APP Pharmaceuticals
  • Barr Pharmaceuticals
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Hospira Inc.
  • Novartis AG
  • Otn Generics Inc.
  • Pharmaforce Inc.
  • Pliva Inc.
  • Sagent Pharmaceuticals
  • Sandoz
  • Strides Arcolab Limited
  • Teva Pharmaceutical Industries Ltd.
Dosage Forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous30 mg/10mL
Injection, powder, lyophilized, for solutionIntravenous90 mg/10mL
Powder, for solutionIntravenous
Powder, for solutionIntravenous60 mg / vial
Powder, for solutionIntravenous30 mg / vial
SolutionIntravenous90 mg/10ml
Powder, for solutionIntravenous90 mg / vial
LiquidIntravenous3 mg / mL
Injection, powder, lyophilized, for solutionIntravenous15 mg
Injection, powder, lyophilized, for solutionIntravenous30 mg
Injection, powder, lyophilized, for solutionIntravenous60 mg
Injection, powder, for solutionIntravenous90 mg
Injection, powder, lyophilized, for solutionIntravenous90 mg
Injection, solution, concentrateIntravenous90 mg/10ml
Injection, solution, concentrateIntravenous3 mg/ml
Injection, solution, concentrateIntravenous6 mg/ml
Injection, solution, concentrateIntravenous9 mg/ml
InjectionIntravenous3 mg/1mL
InjectionIntravenous9 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous3 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous6 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous9 mg/1mL
Injection, solutionIntravenous3 mg/1mL
Injection, solutionIntravenous6 mg/1mL
Injection, solutionIntravenous9 mg/1mL
SolutionIntravenous3 mg/1mL
SolutionIntravenous6 mg/1mL
SolutionIntravenous9 mg/1mL
Solution, concentrateIntravenous3 mg/1mL
Solution, concentrateIntravenous9 mg/1mL
SolutionIntravenous3 mg / mL
SolutionIntravenous6 mg / mL
SolutionIntravenous3.0 mg / mL
SolutionIntravenous6.0 mg / mL
SolutionIntravenous9.0 mg / mL
PowderParenteral15 MG/5ML
PowderParenteral30 MG/10ML
PowderParenteral60 MG/10ML
PowderParenteral90 MG/10ML
InjectionIntravenous3 mg/ml
InjectionIntravenous9 mg/ml
InjectionIntravenous90 MG/10ML
Injection, solution, concentrateIntravenous
Powder, for solutionIntravenous15 mg / vial
Injection, solutionParenteral15 MG/5ML
Injection, solutionParenteral30 MG/10ML
Injection, solutionParenteral60 MG/10ML
Injection, solutionParenteral90 MG/10ML
SolutionIntravenous9 mg / mL
Injection, solution, concentrateIntravenous15 mg/5ml
Prices
Unit descriptionCostUnit
Aredia 90 mg vial839.59USD each
Pamidronate disod 90 mg vial755.64USD each
Aredia 90 mg/vial548.05USD vial
Aredia 30 mg vial279.86USD each
Pamidronate Disodium 90 mg/vial258.28USD vial
Pamidronate Disodium Omega 90 mg/vial258.28USD vial
Pms-Pamidronate 90 mg/vial258.28USD vial
Aredia 30 mg/vial182.69USD vial
Pamidronate Disodium 60 mg/vial129.14USD vial
Pamidronate disod 30 mg vial111.94USD each
Pamidronate Disodium 30 mg/vial86.09USD vial
Pamidronate Disodium Omega 30 mg/vial86.09USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)254-262ChemSpider
Predicted Properties
PropertyValueSource
Water Solubility15.8 mg/mLALOGPS
logP-1.4ALOGPS
logP-4.5Chemaxon
logS-1.2ALOGPS
pKa (Strongest Acidic)0.67Chemaxon
pKa (Strongest Basic)9.86Chemaxon
Physiological Charge-2Chemaxon
Hydrogen Acceptor Count8Chemaxon
Hydrogen Donor Count6Chemaxon
Polar Surface Area161.31 Å2Chemaxon
Rotatable Bond Count4Chemaxon
Refractivity42.62 m3·mol-1Chemaxon
Polarizability17.34 Å3Chemaxon
Number of Rings0Chemaxon
Bioavailability1Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption-0.9635
Blood Brain Barrier+0.6175
Caco-2 permeable-0.6924
P-glycoprotein substrateNon-substrate0.6937
P-glycoprotein inhibitor INon-inhibitor0.937
P-glycoprotein inhibitor IINon-inhibitor0.9868
Renal organic cation transporterNon-inhibitor0.9254
CYP450 2C9 substrateNon-substrate0.8427
CYP450 2D6 substrateNon-substrate0.7949
CYP450 3A4 substrateNon-substrate0.6827
CYP450 1A2 substrateNon-inhibitor0.7892
CYP450 2C9 inhibitorNon-inhibitor0.9049
CYP450 2D6 inhibitorNon-inhibitor0.9336
CYP450 2C19 inhibitorNon-inhibitor0.9049
CYP450 3A4 inhibitorNon-inhibitor0.8539
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9924
Ames testNon AMES toxic0.6692
CarcinogenicityNon-carcinogens0.7877
BiodegradationReady biodegradable0.6385
Rat acute toxicity1.7722 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8231
hERG inhibition (predictor II)Non-inhibitor0.8926
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-MSsplash10-001i-9010000000-c609aeb84dc854acef5e
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-001i-9040000000-f4c409a9c97500f29937
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-0090000000-aee21797c786ae2e7407
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-000i-0970000000-90566973ba94566c8de8
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-03e9-9000000000-57db758a0656fb4481a5
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-03di-9000000000-5a63a0e8491ead7d58a8
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0080-9500000000-4d73f3515952cbd8bf9a
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-144.852441
predicted
DarkChem Lite v0.1.0
[M-H]-144.257341
predicted
DarkChem Lite v0.1.0
[M-H]-130.70215
predicted
DeepCCS 1.0 (2019)
[M+H]+144.361941
predicted
DarkChem Lite v0.1.0
[M+H]+145.001941
predicted
DarkChem Lite v0.1.0
[M+H]+134.53038
predicted
DeepCCS 1.0 (2019)
[M+Na]+144.131741
predicted
DarkChem Lite v0.1.0
[M+Na]+144.235841
predicted
DarkChem Lite v0.1.0
[M+Na]+143.32399
predicted
DeepCCS 1.0 (2019)

Targets

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Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
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Kind
Protein
Organism
Humans
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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  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. [Article]
  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. [Article]
  4. Notarnicola M, Messa C, Cavallini A, Bifulco M, Tecce MF, Eletto D, Di Leo A, Montemurro S, Laezza C, Caruso MG: Higher farnesyl diphosphate synthase activity in human colorectal cancer inhibition of cellular apoptosis. Oncology. 2004;67(5-6):351-8. [Article]
  5. Riebeling C, Forsea AM, Raisova M, Orfanos CE, Geilen CC: The bisphosphonate pamidronate induces apoptosis in human melanoma cells in vitro. Br J Cancer. 2002 Jul 29;87(3):366-71. [Article]
  6. Zhang PL, Lun M, Siegelmann-Danieli N, Blasick TM, Brown RE: Pamidronate resistance and associated low ras levels in breast cancer cells: a role for combinatorial therapy. Ann Clin Lab Sci. 2004 Summer;34(3):263-70. [Article]
Kind
Small molecule
Organism
Humans
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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
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
Uniprot Name
Geranylgeranyl pyrophosphate synthase
Molecular Weight
34870.625 Da
References
  1. Cremers S, Drake MT, Ebetino FH, Bilezikian JP, Russell RGG: Pharmacology of bisphosphonates. Br J Clin Pharmacol. 2019 Jun;85(6):1052-1062. doi: 10.1111/bcp.13867. Epub 2019 Feb 28. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Activator
General Function
Phospholipase a2 activator activity
Specific Function
Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' ...
Gene Name
CASP3
Uniprot ID
P42574
Uniprot Name
Caspase-3
Molecular Weight
31607.58 Da
References
  1. Wada A, Fukui K, Sawai Y, Imanaka K, Kiso S, Tamura S, Shimomura I, Hayashi N: Pamidronate induced anti-proliferative, apoptotic, and anti-migratory effects in hepatocellular carcinoma. J Hepatol. 2006 Jan;44(1):142-50. doi: 10.1016/j.jhep.2005.09.022. Epub 2005 Nov 9. [Article]
  2. Riebeling C, Forsea AM, Raisova M, Orfanos CE, Geilen CC: The bisphosphonate pamidronate induces apoptosis in human melanoma cells in vitro. Br J Cancer. 2002 Jul 29;87(3):366-71. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Activator
General Function
Involved in the activation cascade of caspases responsible for apoptosis execution. Binding of caspase-9 to Apaf-1 leads to activation of the protease which then cleaves and activates caspase-3. Promotes DNA damage-induced apoptosis in a ABL1/c-Abl-dependent manner. Proteolytically cleaves poly(ADP-ribose) polymerase (PARP).
Specific Function
Cysteine-type endopeptidase activity
Gene Name
CASP9
Uniprot ID
P55211
Uniprot Name
Caspase-9
Molecular Weight
46280.325 Da
References
  1. Wada A, Fukui K, Sawai Y, Imanaka K, Kiso S, Tamura S, Shimomura I, Hayashi N: Pamidronate induced anti-proliferative, apoptotic, and anti-migratory effects in hepatocellular carcinoma. J Hepatol. 2006 Jan;44(1):142-50. doi: 10.1016/j.jhep.2005.09.022. Epub 2005 Nov 9. [Article]
  2. Riebeling C, Forsea AM, Raisova M, Orfanos CE, Geilen CC: The bisphosphonate pamidronate induces apoptosis in human melanoma cells in vitro. Br J Cancer. 2002 Jul 29;87(3):366-71. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 16:48