Identification

Name
Nedaplatin
Accession Number
DB13145
Type
Small Molecule
Groups
Approved, Investigational
Description

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.

Structure
Thumb
Synonyms
  • (glycolato-O,O')diammineplatinum(II)
  • CDGP
  • cis-Diammine (glycolato)platinum
  • cis-diammine(glycolato)platinum
  • cis-Diammine(glycolato)platinum(II)
External IDs
254-S / CCRIS 4088 / NSC 375101D
International/Other Brands
Aqupla (Shionogi & Co., Ltd)
Categories
UNII
8UQ3W6JXAN
CAS number
95734-82-0
Weight
Average: 303.181
Monoisotopic: 303.018284
Chemical Formula
C2H8N2O3Pt
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]

Pharmacology

Indication

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

Structured Indications
Not Available
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
UGlutathione
ligand
Human
ADNA
ligand
Human
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].

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].

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Nedaplatin.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Nedaplatin.Experimental
BevacizumabBevacizumab may increase the cardiotoxic activities of Nedaplatin.Approved, Investigational
CabazitaxelNedaplatin may increase the myelosuppressive activities of Cabazitaxel.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Nedaplatin.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Nedaplatin.Experimental
DeslanosideDeslanoside may decrease the cardiotoxic activities of Nedaplatin.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Nedaplatin.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Nedaplatin.Approved
DocetaxelNedaplatin may increase the myelosuppressive activities of Docetaxel.Approved, Investigational
FosphenytoinThe serum concentration of Fosphenytoin can be decreased when it is combined with Nedaplatin.Approved
GitoformateGitoformate may decrease the cardiotoxic activities of Nedaplatin.Experimental
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Nedaplatin.Experimental
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Nedaplatin.Experimental
OleandrinOleandrin may decrease the cardiotoxic activities of Nedaplatin.Experimental, Investigational
OuabainOuabain may decrease the cardiotoxic activities of Nedaplatin.Approved
PaclitaxelNedaplatin may increase the myelosuppressive activities of Paclitaxel.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Nedaplatin.Experimental
PhenytoinThe serum concentration of Phenytoin can be decreased when it is combined with Nedaplatin.Approved, Vet Approved
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Nedaplatin.Experimental
TopotecanThe risk or severity of adverse effects can be increased when Nedaplatin is combined with Topotecan.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Nedaplatin.Approved, Investigational
Food Interactions
Not Available

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. [PubMed:20593091]
  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. [PubMed:27417937]
  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. [PubMed:26886018]
  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. [PubMed:2647312]
  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. [PubMed:12895194]
External Links
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
1CompletedTreatmentEsophageal Cancers1
1RecruitingTreatmentSquamous Cell Carcinoma of Esophagus1
1, 2CompletedTreatmentNasopharyngeal Carcinoma1
1, 2CompletedTreatmentNeoplasms, Esophageal1
2CompletedTreatmentEsophageal Cancers / Squamous Cell Carcinoma (SCC)1
2CompletedTreatmentOesophageal Carcinoma1
2Not Yet RecruitingTreatmentNasopharyngeal Carcinoma1
2Not Yet RecruitingTreatmentRecurrent and Metastatic Nasopharyngeal Carcinoma1
2RecruitingTreatmentCervical Cancers / Complications1
2RecruitingTreatmentNasopharyngeal Carcinoma1
2RecruitingTreatmentNeoplasms, Esophageal1
2RecruitingTreatmentSquamous Cell Carcinoma of Esophagus1
2TerminatedTreatmentNasopharyngeal Carcinoma1
2Unknown StatusTreatmentTumors, Central Nervous System1
3CompletedTreatmentNasopharyngeal Carcinoma1
3RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
3RecruitingTreatmentNasopharyngeal Carcinoma2
3Unknown StatusTreatmentNasopharyngeal Carcinoma1
4CompletedTreatmentSquamous Cell Carcinoma (SCC)1
Not AvailableUnknown StatusTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)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

Taxonomy

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
Carboxylic acid salt / Organic transition metal salt / Monocarboxylic acid or derivatives / Carboxylic acid / Organic nitrogen compound / Organic oxygen compound / Organic oxide / Hydrocarbon derivative / Organic salt / Alkoxide
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
platinum coordination entity (CHEBI:31898)

Targets

Kind
Small molecule
Organism
Human
Pharmacological action
Unknown
Actions
Ligand
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. [PubMed:26886018]
2. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
Yes
Actions
Ligand
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
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. [PubMed:26886018]

Drug created on November 15, 2016 15:30 / Updated on November 09, 2017 05:19