Zoledronic acid

Identification

Summary

Zoledronic acid is a bisphosphonate used to treat malignancy associated hypercalcemia, multiple myeloma, and bone metastasis from solid tumors.

Brand Names

Aclasta, Reclast, Zometa

Generic Name

Zoledronic acid

DrugBank Accession Number

DB00399

Background

Zoledronic acid, or CGP 42'446,⁸ is a third generation, nitrogen containing bisphosphonate similar to ibandronic acid, minodronic acid, and risedronic acid.⁵ Zoledronic acid is used to treat and prevent multiple forms of osteoporosis, hypercalcemia of malignancy, multiple myeloma, bone metastases from solid tumors, and Paget’s disease of bone.^14,15,16 Zoledronic acid was first described in the literature in 1994.⁸

Zoledronic acid was granted FDA approval on 20 August 2001.¹⁴

Type

Small Molecule

Groups

Approved

Structure

3D

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MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Zoledronic acid (DB00399)

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Weight

Average: 272.0896
Monoisotopic: 271.996323708

Chemical Formula

C₅H₁₀N₂O₇P₂

Synonyms

• (1-hydroxy-2-(1H-imidazol-1-yl)ethylidene)bisphosphonic acid
• (1-hydroxy-2-imidazol-1-ylethylidene)diphosphonic acid
• ácido zoledrónico
• Anhydrous Zoledronic Acid
• Nanoparticles containing Zoledronic acid
• Zol
• Zoledronate
• Zoledronic acid
• Zoledronic Acid Anhydrous
• Zoledronic Acid, Anhydrous

External IDs

• CGP 42446
• CGP-42446

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Pharmacology

Indication

Zoledronic acid is indicated to treat hypercalcemia of malignancy, multiple myeloma, bone metastases from solid tumors, osteoporosis in men and postmenopausal women, glucocorticoid induced osteoporosis, and Paget's disease of bone in men and women.^14,15,16 Zoledronic acid is also indicated for the prevention of osteoporosis in post menopausal women and glucocorticoid induced osteoporosis.^14,15,16

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Used as adjunct in combination to treat	Bone metastases		••••••••••••			•••••••••
Treatment of	Hypercalcemia of malignancy		••••••••••••			•••••••••
Used as adjunct in combination to treat	Multiple myeloma (mm)		••••••••••••			•••••••••
Treatment of	Osteoporosis		••••••••••••		•••••••••••••• •••••	•••••••••• ••••••••• ••••••••
Prevention of	Osteoporosis		••••••••••••		••••••••••	•••••••••• ••••••••• ••••••••

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Associated Therapies

• Bone Mineral Density

Contraindications & Blackbox Warnings

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Pharmacodynamics

Zoledronic acid is a third generation, nitrogen containing bisphosphonate that inhibits osteoclast function and prevents bone resorption.⁵ The therapeutic window is wide as patients are unlikely to suffer severe effects from overdoses and the duration of action is long.^14,15,16 Patients should be counselled regarding the risk of electrolyte deficiencies, renal impairment, osteonecrosis of the jaw, atypical femoral fractures, bronchoconstriction, hepatic impairment, hypocalcemia, and embryo-fetal toxicity.^14,15,16

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.⁶ Endocytic vesicles become acidified, releasing bisphosphonates into the cytosol of osteoclasts where they act.⁶

Osteoclasts mediate resorption of bone.⁷ When osteoclasts bind to bone they form podosomes, ring structures of F-actin.⁷ Etidronic acid also inhibits V-ATPases in the osteoclast, though the exact subunits are unknown, preventing F-actin from forming podosomes.^12,13,11 Disruption of the podosomes causes osteoclasts to detach from bones, preventing bone resorption.⁷

Nitrogen containing bisphosphonates such as zoledronate 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.^10,9 These components are essential for post-translational prenylation of GTP-binding proteins like Rap1.^10,9 The lack of prenylation of these proteins interferes with their function, and in the case of Rap1, leads to apoptosis.^10,9 zoledronate also activated caspases which further contribute to apoptosis.^10,9

Target	Actions	Organism
AGeranylgeranyl pyrophosphate synthase	inhibitor	Humans
AHydroxylapatite	antagonist binder	Humans
AFarnesyl pyrophosphate synthase	inhibitor	Humans

Absorption

A 4mg intravenous dose reaches a C_max of 370±78.5ng/mL, with a T_max of 0.317±0.014h, and an AUC of 788±181ng*h/mL.⁴ A 5mg intravenous dose reaches a C_max of 471±76.1ng/mL, with a T_max of 0.368±0.005h, and an AUC of 917±226ng*h/mL.⁴

Volume of distribution

Not Available

Protein binding

Zoledronic acid is 23-53% protein bound in plasma.^14,15,16

Metabolism

Zoledronic acid is not metabolized in vivio.^14,15,16

Route of elimination

Zoledronic acid is 39 ± 16% eliminated in the urine as the unmetabolized parent drug.^14,15,16

Half-life

Zoledronic acid has a terminal elimination half life of 146 hours.^14,15,16

Clearance

Zoledronic acid has a renal clearance of 3.7 ± 2.0 L/h.^14,15,16

Adverse Effects

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Toxicity

Patients experiencing an overdose may present with renal impairment, hypocalcemia, hypophosphatemia, and hypomagnesemia.^14,15,16 Overdose should be managed through intravenous administration of the insufficient ions.^14,15,16

Pathways

Pathway	Category
Zoledronate Action Pathway	Drug action

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Not Available

Interactions

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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.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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Aceclofenac	The risk or severity of gastrointestinal bleeding can be increased when Aceclofenac is combined with Zoledronic acid.
Acemetacin	The risk or severity of gastrointestinal bleeding can be increased when Acemetacin is combined with Zoledronic acid.
Acetylsalicylic acid	The risk or severity of gastrointestinal bleeding can be increased when Acetylsalicylic acid is combined with Zoledronic acid.
Acyclovir	The risk or severity of nephrotoxicity and hypocalcemia can be increased when Acyclovir is combined with Zoledronic acid.
Adefovir dipivoxil	The risk or severity of nephrotoxicity and hypocalcemia can be increased when Adefovir dipivoxil is combined with Zoledronic acid.

Food Interactions

No interactions found.

Products

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Product Ingredients

Ingredient	UNII	CAS	InChI Key
Zoledronate D,L-Lysine Monohydrate	Not Available	Not Available	Not applicable
Zoledronate disodium	7D7GS1SA24	165800-07-7	IEJZOPBVBXAOBH-UHFFFAOYSA-L
Zoledronate trisodium	ARL915IH66	165800-08-8	HYMYRPXSMHJPGD-UHFFFAOYSA-A
Zoledronic acid hemipentahydrate	1K9U67HDID	Not Available	AZZILOGHCMYHQY-UHFFFAOYSA-N
Zoledronic acid monohydrate	6XC1PAD3KF	165800-06-6	FUXFIVRTGHOMSO-UHFFFAOYSA-N

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Aclasta	Injection, solution	5 mg/100ml	Intravenous	Sandoz Pharmaceuticals D.D.	2016-09-07	Not applicable
Aclasta	Solution	5 mg / 100 mL	Intravenous	Sandoz Canada Incorporated	2005-08-22	Not applicable
Aclasta	Injection, solution	5 mg/100ml	Intravenous	Sandoz Pharmaceuticals D.D.	2016-09-07	Not applicable
Act Zoledronic Acid	Solution	5 mg / 100 mL	Intravenous	Actavis Pharma Company	Not applicable	Not applicable
Act Zoledronic Acid Concentrate	Solution	4 mg / 5 mL	Intravenous	Actavis Pharma Company	Not applicable	Not applicable

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Jamp-zoledronic Acid	Solution	4 mg / 5 mL	Intravenous	Jamp Pharma Corporation	2020-01-20	Not applicable
PMS-zoledronic Acid	Solution	4 mg / 5 mL	Intravenous	Pharmascience Inc	2014-11-25	Not applicable
Taro-zoledronic Acid	Solution	5 mg / 100 mL	Intravenous	Taro Pharmaceuticals, Inc.	2014-04-02	Not applicable
Taro-zoledronic Acid Concentrate	Solution	4 mg / 5 mL	Intravenous	Taro Pharmaceuticals, Inc.	2014-02-26	Not applicable
Val-zoledronic Acid	Solution	4 mg / 5 mL	Intravenous	Bausch Health, Canada Inc.	Not applicable	Not applicable

Unapproved/Other Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End	Region	Image
ZOLDRIA 4 MG/5 ML IV INFUZYON ICIN KONSANTRE COZELTI ICEREN FLAKON, 1 ADET	Zoledronic acid monohydrate (4 mg/5ml)	Injection, solution, concentrate	Intravenous	PHARMADA İLAÇ SAN. VE TİC. A.Ş.	2018-07-31	2024-01-23

Categories

ATC Codes

M05BB08 — Zoledronic acid, calcium and colecalciferol, sequential

• M05BB — Bisphosphonates, combinations
• M05B — DRUGS AFFECTING BONE STRUCTURE AND MINERALIZATION
• M05 — DRUGS FOR TREATMENT OF BONE DISEASES
• M — MUSCULO-SKELETAL SYSTEM

M05BA08 — Zoledronic acid

• M05BA — Bisphosphonates
• M05B — DRUGS AFFECTING BONE STRUCTURE AND MINERALIZATION
• M05 — DRUGS FOR TREATMENT OF BONE DISEASES
• M — MUSCULO-SKELETAL SYSTEM

Drug Categories

• Bisphosphonates
• Bone Density Conservation Agents
• Drugs Affecting Bone Structure and Mineralization
• Drugs for Treatment of Bone Diseases
• Imidazoles
• Musculo-Skeletal System
• Organophosphonates
• Organophosphorus Compounds

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

N-substituted imidazoles / Organic phosphonic acids / Heteroaromatic compounds / Azacyclic compounds / Organopnictogen compounds / Organophosphorus compounds / Organooxygen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives

Substituents

Aromatic heteromonocyclic compound / Azacycle / Azole / Bisphosphonate / Heteroaromatic compound / Hydrocarbon derivative / Imidazole / N-substituted imidazole / Organic nitrogen compound / Organic oxide

Molecular Framework

Aromatic heteromonocyclic compounds

External Descriptors

imidazoles, 1,1-bis(phosphonic acid) (CHEBI:46557)

Affected organisms

• Humans and other mammals

Chemical Identifiers

UNII

70HZ18PH24

CAS number

118072-93-8

InChI Key

XRASPMIURGNCCH-UHFFFAOYSA-N

InChI

InChI=1S/C5H10N2O7P2/c8-5(15(9,10)11,16(12,13)14)3-7-2-1-6-4-7/h1-2,4,8H,3H2,(H2,9,10,11)(H2,12,13,14)

IUPAC Name

[1-hydroxy-2-(1H-imidazol-1-yl)-1-phosphonoethyl]phosphonic acid

SMILES

OC(CN1C=CN=C1)(P(O)(O)=O)P(O)(O)=O

References

Synthesis Reference

Judith Aronhime, Revital Lifshitz-Liron, "Zoledronic acid crystal forms, zoledronate sodium salt crystal forms, amorphous zoledronate sodium salt, and processes for their preparation." U.S. Patent US20050054616, issued March 10, 2005.

US20050054616

General References

1. Lyles KW, Colon-Emeric CS, Magaziner JS, Adachi JD, Pieper CF, Mautalen C, Hyldstrup L, Recknor C, Nordsletten L, Moore KA, Lavecchia C, Zhang J, Mesenbrink P, Hodgson PK, Abrams K, Orloff JJ, Horowitz Z, Eriksen EF, Boonen S: Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007 Nov 1;357(18):1799-809. Epub 2007 Sep 17. [Article]
2. Reid IR, Brown JP, Burckhardt P, Horowitz Z, Richardson P, Trechsel U, Widmer A, Devogelaer JP, Kaufman JM, Jaeger P, Body JJ, Brandi ML, Broell J, Di Micco R, Genazzani AR, Felsenberg D, Happ J, Hooper MJ, Ittner J, Leb G, Mallmin H, Murray T, Ortolani S, Rubinacci A, Saaf M, Samsioe G, Verbruggen L, Meunier PJ: Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl J Med. 2002 Feb 28;346(9):653-61. [Article]
3. Durie BG, Katz M, Crowley J: Osteonecrosis of the jaw and bisphosphonates. N Engl J Med. 2005 Jul 7;353(1):99-102; discussion 99-102. [Article]
4. Shiraki M, Tanaka S, Suzuki H, Ueda S, Nakamura T: Safety, pharmacokinetics, and changes in bone metabolism associated with zoledronic acid treatment in Japanese patients with primary osteoporosis. J Bone Miner Metab. 2017 Nov;35(6):675-684. doi: 10.1007/s00774-016-0806-3. Epub 2016 Dec 20. [Article]
5. 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]
6. 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]
7. 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]
8. Green JR, Muller K, Jaeggi KA: Preclinical pharmacology of CGP 42'446, a new, potent, heterocyclic bisphosphonate compound. J Bone Miner Res. 1994 May;9(5):745-51. doi: 10.1002/jbmr.5650090521. [Article]
9. 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]
10. 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]
11. Russell RG: Bisphosphonates: the first 40 years. Bone. 2011 Jul;49(1):2-19. doi: 10.1016/j.bone.2011.04.022. Epub 2011 May 1. [Article]
12. Qin A, Cheng TS, Pavlos NJ, Lin Z, Dai KR, Zheng MH: V-ATPases in osteoclasts: structure, function and potential inhibitors of bone resorption. Int J Biochem Cell Biol. 2012 Sep;44(9):1422-35. doi: 10.1016/j.biocel.2012.05.014. Epub 2012 May 29. [Article]
13. Duan X, Yang S, Zhang L, Yang T: V-ATPases and osteoclasts: ambiguous future of V-ATPases inhibitors in osteoporosis. Theranostics. 2018 Oct 26;8(19):5379-5399. doi: 10.7150/thno.28391. eCollection 2018. [Article]
14. FDA Approved Drug Products: Zometa Zoledronic Acid Intravenous Injection [Link]
15. FDA Approved Drug Products: Reclast Zoledronic Acid Intravenous Injection [Link]
16. FDA Approved Drug Products: Reclast Zoledronic Acid Injection [Link]

External Links

Human Metabolome Database

HMDB0014543

KEGG Drug

D01968

PubChem Compound

68740

PubChem Substance

46507310

ChemSpider

61986

BindingDB

12578

RxNav

1546014

ChEBI

46557

ChEMBL

CHEMBL924

ZINC

ZINC000003803652

Therapeutic Targets Database

DAP001539

PharmGKB

PA10235

PDBe Ligand

ZOL

RxList

RxList Drug Page

Wikipedia

Zoledronic_acid

PDB Entries

1zw5 / 2e91 / 2f8c / 2f8z / 2f9k / 2q58 / 3ez3 / 3iba / 3ldw / 3n45 …

show 10 more

MSDS

Download (57.9 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
4	Active Not Recruiting	Prevention	Bariatric Surgery Candidates / Bone Loss	1
4	Active Not Recruiting	Treatment	Osteoporosis / Sarcopenia	1
4	Active Not Recruiting	Treatment	Stage I Breast Cancer	1
4	Completed	Prevention	Bariatric Surgery Candidates	1
4	Completed	Prevention	Bone Fractures / Liver Transplantation / Osteoporosis	1

Pharmacoeconomics

Manufacturers

• Novartis pharmaceuticals corp

Packagers

• Novartis AG

Dosage Forms

Form	Route	Strength
Injection, powder, lyophilized, for solution	Intravenous	4 mg
Powder, for solution	Parenteral	4 MG
Injection, solution, concentrate	Intravenous; Parenteral	4 MG/5ML
Injection, solution
Solution		5 mg/100ml
Injection, solution	Intravenous; Parenteral	5 MG/100ML
Injection, solution	Parenteral	5 MG
Solution	Intravenous	5 mg / 100 mL
Solution	Parenteral	5 MG
Solution	Parenteral	5 MG/100ML
Solution	Intravenous	5 mg
Solution	Intravenous	0.8 mg/ml
Solution	Parenteral	4 MG/100ML
Solution	Parenteral	4 MG/5ML
Solution	Parenteral	4 MG
Injection	Intravenous
Solution		0.8000 mg
Solution	Intravenous	4.000 mg
Solution, concentrate	Intravenous	4 mg
Solution	Intravenous	4.625 mg
Injection, solution, concentrate	Intravenous	5 mg/100ml
Solution	Intravenous	4.265 mg
Solution	Intravenous	4.264 mg
Solution	Intravenous	5.33 mg
Solution	Parenteral	4.000 mg
Solution	Intravenous	0.8528 mg
Solution	Intravenous
Solution	Intravenous	0.800 mg
Solution
Solution	Intravenous	5.000 mg
Solution	Intravenous	4 mg / 5 mL
Solution	Intravenous	4.26 mg
Solution	Intravenous	0.04 mg
Solution	Intravenous	4 mg
Injection, solution, concentrate	Intravenous	4.00 mg/5ml
Solution	Intravenous	4.00 mg
Injection, solution, concentrate	Intravenous	4 mg
Injection, powder, lyophilized, for solution	Intravenous; Parenteral	4 mg
Injection	Intravenous	4 mg/5mL
Injection	Intravenous	4 mg/100mL
Injection	Intravenous	5 mg/100mL
Injection, solution	Intravenous	0.04 mg/1mL
Injection, solution	Intravenous	0.05 mg/1mL
Injection, solution	Intravenous	4 mg/100mL
Injection, solution	Intravenous	5 mg/100mL
Injection, solution, concentrate	Intravenous	0.8 mg/1mL
Injection, solution, concentrate	Intravenous	4 mg/5mL
Kit	Intravenous	4 mg/5mL
Solution	Intravenous	4 mg/100mL
Solution	Intravenous	5 mg/100mL
Injection	Intravenous	4 mg
Injection, solution	Intravenous	5 mg
Solution	Parenteral
Injection, solution, concentrate	Intravenous
Solution	Intravenous	4 mg/5ml
Injection, powder, for solution	Intravenous	4 mg
Injection, solution, concentrate	Intravenous	4 mg/100mL
Powder, for solution	Intravenous	4 MG
Solution	Parenteral	4.000 mg
Solution		4 mg/100ml
Injection, solution	Intravenous
Injection, solution, concentrate	Intravenous	4.0 mg/5ml
Powder, for solution	Intravenous	4 mg / vial
Injection, solution		4 mg/100ml
Injection, solution		5 mg/100ml
Injection, solution	Intravenous	4 mg/5ml
Solution		4 mg/5ml

Prices

Unit description	Cost	Unit
Zometa 4 mg/5ml Concentrate 5ml Vial	1095.69USD	vial
Reclast 5 mg/100ml Solution	13.39USD	ml
Reclast 5 mg/100 ml solution	12.88USD	ml

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
US4939130	No	1990-07-03	2013-03-02
CA1338937	No	1997-02-25	2014-02-25
CA1338895	No	1997-02-04	2014-02-04
US8324189	Yes	2012-12-04	2025-11-29
US7932241	Yes	2011-04-26	2028-08-05
US8052987	No	2011-11-08	2023-10-27

Properties

State

Solid

Experimental Properties

Property	Value	Source
water solubility	Sparingly soluble	FDA Label

Predicted Properties

Property	Value	Source
Water Solubility	3.27 mg/mL	ALOGPS
logP	-0.93	ALOGPS
logP	-3.9	Chemaxon
logS	-1.9	ALOGPS
pKa (Strongest Acidic)	0.66	Chemaxon
pKa (Strongest Basic)	6.67	Chemaxon
Physiological Charge	-3	Chemaxon
Hydrogen Acceptor Count	8	Chemaxon
Hydrogen Donor Count	5	Chemaxon
Polar Surface Area	153.11 Å2	Chemaxon
Rotatable Bond Count	4	Chemaxon
Refractivity	52.16 m3·mol-1	Chemaxon
Polarizability	20.1 Å3	Chemaxon
Number of Rings	1	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	Yes	Chemaxon
Ghose Filter	No	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	-	0.9723
Blood Brain Barrier	+	0.825
Caco-2 permeable	-	0.6418
P-glycoprotein substrate	Non-substrate	0.5602
P-glycoprotein inhibitor I	Non-inhibitor	0.943
P-glycoprotein inhibitor II	Non-inhibitor	0.9961
Renal organic cation transporter	Non-inhibitor	0.9366
CYP450 2C9 substrate	Non-substrate	0.8319
CYP450 2D6 substrate	Non-substrate	0.8201
CYP450 3A4 substrate	Non-substrate	0.7551
CYP450 1A2 substrate	Non-inhibitor	0.8531
CYP450 2C9 inhibitor	Non-inhibitor	0.8576
CYP450 2D6 inhibitor	Non-inhibitor	0.8935
CYP450 2C19 inhibitor	Non-inhibitor	0.8319
CYP450 3A4 inhibitor	Non-inhibitor	0.9334
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.9904
Ames test	Non AMES toxic	0.5596
Carcinogenicity	Non-carcinogens	0.8194
Biodegradation	Not ready biodegradable	0.5431
Rat acute toxicity	2.3342 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.8515
hERG inhibition (predictor II)	Non-inhibitor	0.8616

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	splash10-001i-9120000000-239c3921d9c0513b29bf
MS/MS Spectrum - DI-ESI-qTof , Negative	LC-MS/MS	splash10-000i-0910000000-6c7cee1b60ea3968e2f7
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-00di-0590000000-85effe1f71ec78e3a35a
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0fk9-0090000000-dacd042b8005d501192f
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0ik9-9040000000-5ce349a866c3aab5f030
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-00di-0390000000-4e5df6b1956046fc3bd7
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-03fr-9110000000-babdbc8ddf70f2f270ea
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-00lr-9000000000-a7132f68d8c2aaa59953
Predicted 1H NMR Spectrum	1D NMR	Not Applicable
Predicted 13C NMR Spectrum	1D NMR	Not Applicable

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å2)	Source type	Source
[M-H]-	157.2670571	predicted	DarkChem Lite v0.1.0
[M-H]-	155.5622571	predicted	DarkChem Lite v0.1.0
[M-H]-	138.84532	predicted	DeepCCS 1.0 (2019)
[M+H]+	156.1771571	predicted	DarkChem Lite v0.1.0
[M+H]+	155.1736571	predicted	DarkChem Lite v0.1.0
[M+H]+	141.24092	predicted	DeepCCS 1.0 (2019)
[M+Na]+	155.9639571	predicted	DarkChem Lite v0.1.0
[M+Na]+	154.4681571	predicted	DarkChem Lite v0.1.0
[M+Na]+	147.15344	predicted	DeepCCS 1.0 (2019)

Targets

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Binding Properties

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Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	97000	N/A	N/A	A4796
IC 50 (nM)	>100000	N/A	N/A	A28084 / A28083
IC 50 (nM)	100000	7	37	A28085
Ki (nM)	2700	N/A	N/A	A4796

Details

Binding Properties1. Geranylgeranyl pyrophosphate synthase

Kind

Protein

Organism

Humans

Pharmacological action

Yes

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. 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. [Article]

Details2. Hydroxylapatite

Kind

Small molecule

Organism

Humans

Pharmacological action

Yes

Actions

Antagonist

Binder

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]
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. [Article]
3. 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]

Binding Properties

×

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	0.24	N/A	N/A	A28081
IC 50 (nM)	110	N/A	N/A	A27596
IC 50 (nM)	475.3	N/A	N/A	A27597
IC 50 (nM)	4.1	N/A	N/A	A27597 / A28082 / A28083
IC 50 (nM)	3	N/A	N/A	A27598
IC 50 (nM)	475	N/A	N/A	A28083
Ki (nM)	10	N/A	N/A	A27596
Ki (nM)	85.9	N/A	N/A	A27597
Ki (nM)	0.07	N/A	N/A	A27597

Details

Binding Properties3. Farnesyl pyrophosphate synthase

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. 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]
2. Glickman JF, Schmid A: Farnesyl pyrophosphate synthase: real-time kinetics and inhibition by nitrogen-containing bisphosphonates in a scintillation assay. Assay Drug Dev Technol. 2007 Apr;5(2):205-14. [Article]
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. [Article]
4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

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Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:55