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
Structure for Nedaplatin (DB13145)
- 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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Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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.
Target Actions Organism ADNA ligandHumans UGlutathione ligandHumans - 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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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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Nedaplatin which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Nedaplatin which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Nedaplatin which could result in a higher serum level. Acetaminophen Acetaminophen may decrease the excretion rate of Nedaplatin which could result in a higher serum level. Acetazolamide Acetazolamide may increase the excretion rate of Nedaplatin which could result in a lower serum level and potentially a reduction in efficacy. - Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- 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
- 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]
- 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]
- 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]
- 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]
- 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]
- External Links
- MSDS
- Download (164 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Squamous Cell Carcinoma (SCC) 1 3 Completed Treatment Nasopharyngeal Carcinoma (NPC) 1 3 Not Yet Recruiting Treatment Nasopharyngeal Carcinoma (NPC) 1 3 Recruiting Treatment Advanced Non-squamous Cell Non-small Cell Lung Cancer 1 3 Recruiting Treatment Nasopharyngeal 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
Property Value Source water solubility 10 mg/mL MSDS - Predicted Properties
Property Value Source Water Solubility 138.0 mg/mL ALOGPS logP -0.84 ALOGPS logS -0.35 ALOGPS Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 0 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 90.81 Å2 Chemaxon Rotatable Bond Count 0 Chemaxon Refractivity 43.23 m3·mol-1 Chemaxon Polarizability 11.5 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
References
- 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]
References
- 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