Identification

Generic Name
Nedaplatin
DrugBank Accession Number
DB13145
Background

Nedaplatin is a second generation platinum analog 1. It is less nephrotoxic than Cisplatin but has proven equally effective. It was approved for use in Japan in 1995.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 303.181
Monoisotopic: 303.018284
Chemical Formula
C2H8N2O3Pt
Synonyms
  • (glycolato-O,O')diammineplatinum(II)
  • CDGP
  • cis-Diammine (glycolato)platinum
  • cis-diammine(glycolato)platinum
  • cis-Diammine(glycolato)platinum(II)
  • Nedaplatin
External IDs
  • 254-S
  • CCRIS 4088
  • NSC 375101D

Pharmacology

Indication

Used in the treatment of non-small cell lung cancer, small cell lung cancer, oesophygeal cancer, and head and neck cancers 1.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Nedaplatin damages DNA and induces cell death in cancer cells 3. It also functions as a radiosensitizer, increasing the susceptibility of the affected cells to radiation therapy 2.

Mechanism of action

As a platinum analog, nedaplatin likely works similarly to Cisplatin on which the following mechanistic description is based. Once it has entered the cell it is hydrolyzed to its active form which complexes with water molecules 3. This form binds to to nucleophiles in the cytoplasm such as glutathione and other cyteine rich proteins resulting in an overall increase in oxidative stress as the cell loses antioxidant proteins. It also binds to purine nucleotides in the DNA. The active form allows for two binding interactions to form cross-links between these nucleotides. High mobility group proteins-1 and -2 induce apoptosis in response to guanine cross-links and their binding serves to shield the cross-linked DNA from repair mechanisms. The mismatch repair (MMR) protein complex also recognizes the distortion caused by platinum complexes and attempts to repair the DNA. This results in single strand breaks when the MMR complex attempts to remove the platinum cross-link. The MMR complex induces apoptosis after the repair attempt has failed. The single strand break in DNA makes it easier to form lethal double strand breaks with radiation treatment thus creating the radiosensitizing effect of nedaplatin 2.

TargetActionsOrganism
ADNA
ligand
Humans
UGlutathione
ligand
Humans
Absorption

Not Available

Volume of distribution

The volume of distribution of free platinum is 12.0 L 5.

Protein binding

Approximately 50% of the platinum from nedaplatin appears to be bound to human plasma proteins 4.

Metabolism
Not Available
Route of elimination

Most of the platinum from nedaplatin is eliminated in the urine (59.6%) 4.

Half-life

Not Available

Clearance

Clearance of the free platinum is 4.47 L/h 5.

Adverse Effects
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Toxicity

The toxic effects of nedaplatin are likely similar to those of Cisplatin which produces nausea, vomiting, peripheral neuropathy, and ototoxicity 3. A major difference between the compounds is the large reduction in nephrotoxicity of nedaplatin compared to Cisplatin 1.

Pathways
Not Available
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
AbacavirAbacavir may decrease the excretion rate of Nedaplatin which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Nedaplatin which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Nedaplatin which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Nedaplatin which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Nedaplatin which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Nedaplatin which could result in a higher serum level.
AclidiniumAclidinium may decrease the excretion rate of Nedaplatin which could result in a higher serum level.
AcrivastineAcrivastine may decrease the excretion rate of Nedaplatin which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Nedaplatin which could result in a higher serum level.
Adefovir dipivoxilAdefovir dipivoxil may decrease the excretion rate of Nedaplatin which could result in a higher serum level.
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Food Interactions
Not Available

Products

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International/Other Brands
Aqupla (Shionogi & Co., Ltd)

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as carboxylic acid salts. These are ionic derivatives of carboxylic acid.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Carboxylic acid derivatives
Direct Parent
Carboxylic acid salts
Alternative Parents
Organic transition metal salts / Monocarboxylic acids and derivatives / Carboxylic acids / Organic oxides / Organic nitrogen compounds / Hydrocarbon derivatives / Carbonyl compounds / Alkoxides
Substituents
Aliphatic acyclic compound / Alkoxide / Carbonyl group / Carboxylic acid / Carboxylic acid salt / Hydrocarbon derivative / Monocarboxylic acid or derivatives / Organic nitrogen compound / Organic oxide / Organic oxygen compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
platinum coordination entity (CHEBI:31898)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
8UQ3W6JXAN
CAS number
95734-82-0
InChI Key
GYAVMUDJCHAASE-UHFFFAOYSA-M
InChI
InChI=1S/C2H3O3.2H3N.Pt/c3-1-2(4)5;;;/h1H2,(H,4,5);2*1H3;/q-1;;;+2/p-1
IUPAC Name
2,2-diamino-1,3-dioxa-2-platinacyclopentan-4-one
SMILES
[H][N]([H])([H])[Pt]1(OCC(=O)O1)[N]([H])([H])[H]

References

General References
  1. Wheate NJ, Walker S, Craig GE, Oun R: The status of platinum anticancer drugs in the clinic and in clinical trials. Dalton Trans. 2010 Sep 21;39(35):8113-27. doi: 10.1039/c0dt00292e. Epub 2010 Jun 30. [Article]
  2. Fong CW: Platinum based radiochemotherapies: Free radical mechanisms and radiotherapy sensitizers. Free Radic Biol Med. 2016 Oct;99:99-109. doi: 10.1016/j.freeradbiomed.2016.07.006. Epub 2016 Jul 12. [Article]
  3. Dilruba S, Kalayda GV: Platinum-based drugs: past, present and future. Cancer Chemother Pharmacol. 2016 Jun;77(6):1103-24. doi: 10.1007/s00280-016-2976-z. Epub 2016 Feb 17. [Article]
  4. Sasaki Y, Tamura T, Eguchi K, Shinkai T, Fujiwara Y, Fukuda M, Ohe Y, Bungo M, Horichi N, Niimi S, et al.: Pharmacokinetics of (glycolate-0,0')-diammine platinum (II), a new platinum derivative, in comparison with cisplatin and carboplatin. Cancer Chemother Pharmacol. 1989;23(4):243-6. [Article]
  5. Ishibashi T, Yano Y, Oguma T: Population pharmacokinetics of platinum after nedaplatin administration and model validation in adult patients. Br J Clin Pharmacol. 2003 Aug;56(2):205-13. [Article]
KEGG Drug
D01416
KEGG Compound
C12862
PubChem Compound
9548889
PubChem Substance
347829261
ChemSpider
7972206
ChEBI
31898
Wikipedia
Nedaplatin
MSDS
Download (164 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentSquamous Cell Carcinoma (SCC)1
3CompletedTreatmentNasopharyngeal Carcinoma (NPC)1
3Not Yet RecruitingTreatmentNasopharyngeal Carcinoma (NPC)1
3RecruitingTreatmentNasopharyngeal Carcinoma (NPC)1
3RecruitingTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
3Unknown StatusTreatmentNasopharyngeal Carcinoma (NPC)3
3Unknown StatusTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
2CompletedTreatmentEsophageal Cancer / Squamous Cell Carcinoma (SCC)1
2CompletedTreatmentEsophageal Carcinoma1
2CompletedTreatmentNasopharyngeal Carcinoma (NPC)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility10 mg/mLMSDS
Predicted Properties
PropertyValueSource
Water Solubility138.0 mg/mLALOGPS
logP-0.84ALOGPS
logS-0.35ALOGPS
Physiological Charge0Chemaxon
Hydrogen Acceptor Count0Chemaxon
Hydrogen Donor Count0Chemaxon
Polar Surface Area90.81 Å2Chemaxon
Rotatable Bond Count0Chemaxon
Refractivity43.23 m3·mol-1Chemaxon
Polarizability11.5 Å3Chemaxon
Number of Rings1Chemaxon
Bioavailability1Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

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Kind
Nucleotide
Organism
Humans
Pharmacological action
Yes
Actions
Ligand
Curator comments
Binds to nucleophilic sites on purine nucleotides such as N7 and cross links DNA strands.
DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.
References
  1. Dilruba S, Kalayda GV: Platinum-based drugs: past, present and future. Cancer Chemother Pharmacol. 2016 Jun;77(6):1103-24. doi: 10.1007/s00280-016-2976-z. Epub 2016 Feb 17. [Article]
Kind
Small molecule
Organism
Humans
Pharmacological action
Unknown
Actions
Ligand
Curator comments
Hydrolyzed form of drug binds to target.
References
  1. Dilruba S, Kalayda GV: Platinum-based drugs: past, present and future. Cancer Chemother Pharmacol. 2016 Jun;77(6):1103-24. doi: 10.1007/s00280-016-2976-z. Epub 2016 Feb 17. [Article]

Drug created at November 15, 2016 22:30 / Updated at February 21, 2021 18:54