Synonym
AMD473; AMD 473; AMD-473; NX 473; NX473; NX-473; ZD0473; ZD-0473; ZD 0473; Picoplatin.
IUPAC/Chemical Name
Cis-Amminedichloro (2-Methylpyridine) Platinum.
InChi Key
IIMIOEBMYPRQGU-UHFFFAOYSA-L
InChi Code
InChI=1S/C6H7N.2ClH.H3N.Pt/c1-6-4-2-3-5-7-6;;;;/h2-5H,1H3;2*1H;1H3;/q;;;;+2/p-2
SMILES Code
CC1=NC=CC=C1.Cl[Pt]Cl.N
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not soluble in water.
Shelf Life
>5 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Picoplatin is a new generation platinum chemotherapy agent that has an improved safety profile compared to existing platinum-based chemotherapeutics and was designed to overcome platinum resistance. Picoplatin has been evaluated in approximately 1100 patients and has demonstrated activity in multiple indications with no evidence of significant kidney, nerve toxicity or hearing loss. (Source: Poniard's website).
Picoplatin is a cytotoxic platinum compound in clinical development by Poniard Pharmaceuticals (previously NeoRx) for the treatment of patients with solid tumors. In Phase I and Phase II clinical trials, picoplatin demonstrated activity in a variety of solid tumors, including lung, ovarian, colorectal and hormone-refractory prostate cancer. However, in Phase III trials, picoplatin failed to hit its primary endpoint for advanced small cell lung cancer. Hopes are now pinned on its use for metastatic colorectal cancer. (source: wikipedia.com).
Biological target:
Picoplatin is a new generation organic platinum analog with an extended spectrum of antineoplastic activity.
In vitro activity:
The synthesis and characterization of a series of picoplatin-based (picoplatin = [PtCl(2)(mpy)(NH(3))], mpy = 2-methylpyridine), Pt(iv) complexes with axial carboxylato ligands of increasing length are reported. Pt(iv) complexes with n = 0-2 were selected to be tested on four malignant pleural mesothelioma (MPM) cell lines, on human mesothelial cells (HMC), and on the cisplatin-sensitive ovarian A2780 cell line along with cisplatin as a metallo-drug reference. In general, the longer the axial chain, the more cytotoxic and selective the Pt(IV) complex is. Pt(IV) analogs show good activity on the MPM cell lines, approaching or in some case bypassing that of cisplatin and represent quite promising drug candidates for the treatment of tumors whose chemoresistance is mainly based on glutathione overexpression, such as MPM.
Reference: Dalton Trans. 2012 Mar 21;41(11):3313-20. https://pubmed.ncbi.nlm.nih.gov/22286213/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
376.14
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Ravera M, Gabano E, Zanellato I, Bonarrigo I, Escribano E, Moreno V, Font-Bardia M, Calvet T, Osella D. Synthesis, characterization and antiproliferative activity on mesothelioma cell lines of bis(carboxylato)platinum(IV) complexes based on picoplatin. Dalton Trans. 2012 Mar 21;41(11):3313-20. doi: 10.1039/c2dt11874b. Epub 2012 Jan 30. PMID: 22286213.
2. Tang CH, Parham C, Shocron E, McMahon G, Patel N. Picoplatin overcomes resistance to cell toxicity in small-cell lung cancer cells previously treated with cisplatin and carboplatin. Cancer Chemother Pharmacol. 2011 Jun;67(6):1389-400. doi: 10.1007/s00280-010-1435-5. Epub 2010 Aug 31. PMID: 20809122; PMCID: PMC3102205.
In vitro protocol:
1. Ravera M, Gabano E, Zanellato I, Bonarrigo I, Escribano E, Moreno V, Font-Bardia M, Calvet T, Osella D. Synthesis, characterization and antiproliferative activity on mesothelioma cell lines of bis(carboxylato)platinum(IV) complexes based on picoplatin. Dalton Trans. 2012 Mar 21;41(11):3313-20. doi: 10.1039/c2dt11874b. Epub 2012 Jan 30. PMID: 22286213.
2. Tang CH, Parham C, Shocron E, McMahon G, Patel N. Picoplatin overcomes resistance to cell toxicity in small-cell lung cancer cells previously treated with cisplatin and carboplatin. Cancer Chemother Pharmacol. 2011 Jun;67(6):1389-400. doi: 10.1007/s00280-010-1435-5. Epub 2010 Aug 31. PMID: 20809122; PMCID: PMC3102205.
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 Jun 30. [Epub ahead of print] PubMed PMID: 20593091.
2: Margiotta N, Denora N, Ostuni R, Laquintana V, Anderson A, Johnson SW, Trapani G, Natile G. Platinum(II) complexes with bioactive carrier ligands having high affinity for the translocator protein. J Med Chem. 2010 Jul 22;53(14):5144-54. PubMed PMID: 20568783.
3: More SS, Li S, Yee SW, Chen L, Xu Z, Jablons DM, Giacomini KM. Organic cation transporters modulate the uptake and cytotoxicity of picoplatin, a third-generation platinum analogue. Mol Cancer Ther. 2010 Apr;9(4):1058-69. Epub 2010 Apr 6. PubMed PMID: 20371711.
4: Olszewski U, Hamilton G. A better platinum-based anticancer drug yet to come? Anticancer Agents Med Chem. 2010 May 1;10(4):293-301. Review. PubMed PMID: 20187870.
5: Eckardt JR, Bentsion DL, Lipatov ON, Polyakov IS, Mackintosh FR, Karlin DA, Baker GS, Breitz HB. Phase II study of picoplatin as second-line therapy for patients with small-cell lung cancer. J Clin Oncol. 2009 Apr 20;27(12):2046-51. Epub 2009 Mar 16. PubMed PMID: 19289620.
6: Shah N, Dizon DS. New-generation platinum agents for solid tumors. Future Oncol. 2009 Feb;5(1):33-42. Review. PubMed PMID: 19243296.
7: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2008 Oct;30(8):643-72. PubMed PMID: 19088949.
8: Tomillero A, Moral MA. Gateways to clinical trials. July-August 2008. Methods Find Exp Clin Pharmacol. 2008 Jul-Aug;30(6):459-95. PubMed PMID: 18850047.
9: Teicher BA. Newer cytotoxic agents: attacking cancer broadly. Clin Cancer Res. 2008 Mar 15;14(6):1610-7. Review. PubMed PMID: 18347161.
