129580-63-8

Basic information

• Product Name: Satraplatin
• Synonyms: bis(acetato-o)amminedichloro(cyclohexanamine)-pt;platinum (lv) cis-dichloro-trans-bis(acetato-o)ammine(cyclohexanamine);SATRAPLATIN;JM 216;Bis-acetatoamminedichlorocyclohexylamine platinum(iv);C081294;Platinum, bis(acetato-o)amminedichloro(cyclohexanamine)-, (oc-6-43)-;Satraplatin(JM216)
• CAS NO: 129580-63-8
• Molecular Formula: C₁₀H₂₂Cl₂N₂O₄Pt
• Molecular Weight: 500.28
• Product Categories: Anticancer
• Mol File: 129580-63-8.mol

Chemical Properties

• Boiling Point: 134.5 °C at 760 mmHg
• Flash Point: 32.2 °C
• Appearance: /
• Vapor Pressure: 8.07mmHg at 25°C
• CAS DataBase Reference: Satraplatin(CAS DataBase Reference)
• NIST Chemistry Reference: Satraplatin(129580-63-8)
• EPA Substance Registry System: Satraplatin(129580-63-8)

Safety Data

• Hazardous Substances Data: 129580-63-8(Hazardous Substances Data)

Usage

Uses

Used in Antineoplastic Applications:
Satraplatin is used as an antineoplastic agent for the treatment of advanced prostate cancer. It modulates several oncological signaling pathways, exerting inhibitory effects on tumor growth and progression. Additionally, it demonstrates synergistic anticancer effects when combined with conventional chemotherapeutic drugs, enhancing chemo-sensitivity and efficacy in resistant cases.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, Satraplatin is used as a key component in the development of new drugs for cancer treatment. Its unique chemical structure and properties make it a valuable asset in the fight against various types of cancer, particularly prostate cancer.

Pharmaceutical Applications

Satraplatin (JM216, cis,trans,cis-[PtCl2(OAc)2(NH3)(C6H5NH2)]) is a Pt(IV) or Pt4+ complex, which is active by oral administration, as it is more hydrophobic than cisplatin. This form of administration is very attractive because of the convenience and freedom it provides to the patient. Satraplatin also has a milder toxicity profile and is shows no cross-resistance with cisplatin. Satraplatin in combination with prednisone has completed phase III clinical trials against hormone-refractory prostate cancer. The results were very encouraging, but the overall survival rate did not improve significantly enough. As a result, the fast-track approval of the FDA was not granted.Structurally, satraplatin consists of a Pt(IV) centre, which is coordinated by six ligands forming a close to octahedral geometry. In general, octahedral Pt(IV) complexes (low-spin d6) are much more kinetically inert than square planar Pt(II) complexes.

Clinical Use

This newest organometallic agent currently is in clinical trials as a second-line agent for the treatment of hormone-refractory prostate cancer . There is hope that it also will find value in ovarian cancer and small cell lung cancer.

Side effects

As with other organoplatinum complexes, the diaquo form is active. At this early stage, the toxicity profile appears to be mild, with dose-related myelosuppression, particularly neutropenia and thrombocytopenia, being the major use-limiting side effect.

Metabolism

Unlike the square-planar Pt(II) complexes currently on the market, it is active by the oral route. It is metabolized quickly in whole blood, producing up to six metabolites. The major metabolite is the desacetoxy analogue.

InChI:InChI=1/C6H13N.2C2H4O2.2ClH.H3N.Pt/c7-6-4-2-1-3-5-6;2*1-2(3)4;;;;/h6H,1-5,7H2;2*1H3,(H,3,4);2*1H;1H3;/q;;;;;;+4/p-4

Upstream product

• 124721-03-5 trans,trans,trans-[PtCl₂(OH)2(c-C₆H₁₁NH₂)(NH₃)] 
• 108-24-7 acetic anhydride 
• 124721-03-5 trans,cis,cis-Pt(NH₃)(cyclohexylamine)Cl₂(OH)2 

Downstream Products

• 921593-87-5 trans-Pt(acetate)2(cyclohexylamine)NH₃ 
• 159701-67-4 trans-[PtCl₂(NH₃)(cyclohexylamine)] 
• 921593-87-5 cis-Pt(acetate)2(cyclohexylamine)NH₃ 

Relevant articles and documents

Crystal and Molecular Structures of Asymmetric cis- and trans-Platinum(II/IV) Compounds and Their Reactions with DNA Fragments

The asymmetrically substituted platinum(II) complexes cis-Pt(NH3)(c-C5H11NH2)Cl 2 and trans-Pt(NH3)(c-C6H11-NH2)Cl 2 have been synthesized and their crystal structures have been determined. Crystals of cis-Pt(NH3)(c-C6H11NH2)Cl 2 (1) are orthorhombic, space group Pbca (no. 61) with a = 10.1994(12), b = 10.494(2), c = 18.826(2) ?, Z = 8. The structure refinement converged to R1 = 0.0518 and wR2 = 0.1143. Crystals of trans-Pt(NH3)(c-C6H11NH2)Cl 2 (2) are monoclinic, space group P21/c (no. 14) with a = 12.141(3), b = 6.0965(9), c = 19.864(3) ?, β= 118.71(2)°, Z = 4. The structure refinement converged to R1 = 0.0711 and wR2 = 0.1846. In addition, the Pt(IV) analogues with axial hydroxide ligands have been synthesized. Also the corresponding bis(carboxylato)-platinum(IV) compound of formula trans,cis,cis-Pt(NH3)(c-C6H11NH 2)Cl2(OOCCH3)2 has been obtained by conversion of the hydroxide with acetic anhydride. Reactions of these platinum complexes with 9-methylhy-poxanthine and guanosine-5′-monophosphate (5′-GMP) have been studied in significant detail. The course of the reactions was followed by NMR spectroscopy, and 1H and 195Pt techniques were used to identify the formation of the products. It was found that the Pt(II) compounds easily react with the bases at the N7 position, whereas the Pt(IV) compounds react very slowly (for trans,cis,cis-Pt(NH3)(c-C6H11NH 2)Cl2(OOCCH3)2) or not at all (for trans,trans,trans-Pt(NH3)(c-C6H11NH 2)Cl2(OH)2). Only in the presence of glutathione does a reaction of the latter with 5′-GMP takes place. In this case a major product was found to be the reduced trans-Pt(II) complex with one molecule of 5′-GMP and one molecule of S-bonded glutathione.

Studies on the oral anticancer drug JM-216: Synthesis and characterization of isomers and related complexes

The complex cis,trans,cis-[PtCl2(OAc)2NH3(c-C 6H11NH2)] (JM-216) is currently undergoing clinical evaluation as an antitumor agent. In support of characterization and analysis of this complex a study of its isomers and other complexes [PtClm(OAc)4-mNH3(c-C6H 11NH2)] (m = 0-4) has been undertaken. The complexes have been obtained by a variety of synthetic routes which now extend the scope for the preparation of platinum(IV) antitumor complexes. As platinum(IV) complexes are very stable to substitution in the absence of catalysis, use has been made of both light and base catalysis to promote substitution. Oxidative addition to platinum(II) using hypervalent iodine reagents has also been used. The stereochemistry of the complexes has been confirmed by spectroscopic studies, primarily NMR including natural abundance 15N NMR spectroscopy.