Satraplatin
(Synonyms: 沙铂; BMS182751; BMY45594; JM216) 目录号 : GC37593
An orally available antineoplastic platinum(IV) complex
Cas No.:129580-63-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | Cells are harvested, counted and distributed to microtiter plates in 100 μL medium at a density of 1×104 cells/well. Appropriate dilutions of test compounds (Satraplatin, etc.) are added to a total volume of 200 μL/well and plates incubated under tissue culture conditions for four days. Stock solutions of the compounds are prepared in either 70% ethanol or DMSO and diluted more than 100-fold for the assays. Solvent controls are included in all tests. Dose response curves are obtained by assessing cell proliferation at twofold drug dilutions in triplicate and used for calculation of IC50 values. Cell growth is quantified using a modified tetrazolium dye assay (MTT) and by measurement of the reduced formazane dye at 450 nm wavelength (medium control set to 100% proliferation)[1]. |
References: [1]. Fiebiger W, et al. In vitro cytotoxicity of novel platinum-based drugs and dichloroacetate against lung carcinoid cell lines. Clin Transl Oncol. 2011 Jan;13(1):43-9. | |
Satraplatin is an orally available antineoplastic platinum(IV) complex.1 It is more hydrophobic than cisplatin or oxaliplatin , which reduces transport-determined acquired resistance.1 Satraplatin also displays less neurotoxicity in rats than cisplatin or tetraplatin.2 Satraplatin has a favorable toxicity profile and appears to have clinical activity against a variety of malignancies.3
1.Kelland, L.R., Abel, G., McKeage, M.J., et al.Preclinical antitumor evaluation of bis-acetato-ammine-dichloro-cyclohexylamine platinum(IV): An orally active platinum drugCancer Res.53(11)2581-2586(1993) 2.McKeage, M.J., Boxall, F.E., Jones, M., et al.Lack of neurotoxicity of oral bisacetatoamminedichlorocyclohexylamine-platinum(IV) in comparison to cisplatin and tetraplatin in the ratCancer Res.54(3)629-631(1994) 3.Bhargava, A., and Vaishampayan, U.N.Satraplatin: Leading the new generation of oral platinum agentsExpert. Opin. Investig. Drugs18(11)1787-1797(2009)
| Cas No. | 129580-63-8 | SDF | |
| 别名 | 沙铂; BMS182751; BMY45594; JM216 | ||
| Canonical SMILES | [Cl-][Pt+4]([O-]C(C)=O)([O-]C(C)=O)([Cl-])([NH3])[NH2]C1CCCCC1 | ||
| 分子式 | C10H22Cl2N2O4Pt | 分子量 | 500.28 |
| 溶解度 | DMSO: ≥ 33 mg/mL (65.96 mM; DMSO can inactivate Satraplatin's activity) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9989 mL | 9.9944 mL | 19.9888 mL |
| 5 mM | 0.3998 mL | 1.9989 mL | 3.9978 mL |
| 10 mM | 0.1999 mL | 0.9994 mL | 1.9989 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Satraplatin: leading the new generation of oral platinum agents
Expert Opin Investig Drugs 2009 Nov;18(11):1787-97.PMID:19888874DOI:10.1517/13543780903362437.
Background: In recent years, JM-216/Satraplatin (GPC Biotech, Inc.) has emerged as a novel oral platinum analogue with a better toxicity profile than cisplatin. Since Satraplatin is more hydrophobic than cisplatin or oxaliplatin, it appears to demonstrate efficacy in cisplatin-resistant cell lines. The preclinical and clinical evaluation of Satraplatin stimulated this review of the pharmacology and clinical trial data of this agent. Methods: A literature review was conducted in the MEDLINE database from 1985 to present using the keywords 'Satraplatin' or 'JM-216'. The abstracts regarding Satraplatin reported at the 2007 - 2009 American Society of Clinical Oncology meetings were also reviewed. Results/conclusion: Satraplatin has a favorable toxicity profile, and appears to have clinical activity against a variety of malignancies such as breast, prostate and lung cancer. The oral route of administration and the intermittent schedule makes it very convenient for clinical use. Despite this, a FDA-approved indication has not yet been achieved. The only Phase III trial with Satraplatin was conducted in pretreated metastatic castrate-resistant prostate cancer (CRPC), revealing an improvement in progression-free survival but no overall survival benefit. Future development would have to include designing trials in docetaxel-refractory metastatic CRPC, or in other malignancies where cisplatin is of benefit.
Satraplatin for the therapy of castration-resistant prostate cancer
Future Oncol 2009 Sep;5(7):931-40.PMID:19792961DOI:10.2217/fon.09.84.
While docetaxel-based chemotherapy improves survival in patients with castration-resistant prostate cancer, all of these patient's cancers will eventually progress and other active treatment agents are necessary. Satraplatin is a third-generation orally-available platinum analog that demonstrated a 33% reduction in the risk of progression in patients with metastatic castration-resistant prostate cancer following one prior chemotherapy regimen in the large Phase III Satraplatin and Prednisone Against Refractory Cancer (SPARC) trial. Satraplatin also demonstrated beneficial effects on pain and displayed evidence of biological activity with prostate-specific antigen level declines and objective response rates. Satraplatin did not significantly extend survival, although this analysis may have been confounded by post-study therapy. Further development is ongoing with the evaluation of combination regimens containing Satraplatin in other solid tumors. In addition, efforts are ongoing to select patients who are more likely to benefit from Satraplatin.
Satraplatin Demonstrates High Cytotoxic Activity Against Genetically Defined Lymphoid Malignancies
Anticancer Res 2022 Apr;42(4):1821-1832.PMID:35347000DOI:10.21873/anticanres.15658.
Background/aim: Satraplatin is an oral platinum analog with proven clinical efficacy and a more favorable toxicity profile, although with increased hematotoxicity, when compared to cisplatin. Hence, we carried out a systematic biomarker analysis to identify hematological malignancies with high susceptibility to Satraplatin. Materials and methods: Half-maximal inhibitory concentrations (IC50) for Satraplatin and cisplatin were determined for 66 different cancer cell lines by CTG Luminescent Cell Viability Assay. In a second step, whole transcriptome RNA sequencing and whole-exome DNA sequencing technology followed by unbiased analysis of gene expression, gene mutation and copy number levels were performed and correlated with drug efficacy. Results: Satraplatin was significantly more active against hematological malignancies compared to solid organ cancer. In addition, Satraplatin showed a significantly more potent antiproliferative activity compared to cisplatin in most lymphoma cell lines achieving sub micromolar IC50 values. Single BCL2 apoptosis regulator (BCL2) gene mutation and 9p21 copy-number deletions including S-methyl-5'-thioadenosine phosphorylase (MTAP) deficiency were identified as key characteristics for high sensitivity to Satraplatin. Conclusion: Satraplatin demonstrated a high cytotoxic activity in genetically well-defined hematological malignancies which is distinct from that of cisplatin. MTAP deficiency was identified as biomarker of enhanced Satraplatin efficacy in hematological cancer-derived cell lines. These data in combination with the lipophilicity of Satraplatin provide the rationale for targeting specific lymphatic entities such as primary central nervous system lymphoma and cutaneous T-cell lymphoma to improve clinical outcome.
Satraplatin: an orally available platinum analog for the treatment of cancer
Expert Rev Anticancer Ther 2006 Jul;6(7):973-82.PMID:16831070DOI:10.1586/14737140.6.7.973.
Satraplatin is a novel, orally bioavailable, platinum anticancer drug. Platinum analogs form the mainstay of treatment for a number of cancers, including lung, ovarian, colorectal and head and neck cancer. A disadvantage of the currently marketed platinum analogs is that they must all be administered via intravenous infusion. In addition, their utility is often limited by toxicity, particularly neurotoxicity, ototoxicity and renal toxicity. Satraplatin has preclinical antitumor activity comparable with that of cisplatin and, clinically, has a more manageable side-effect profile. Satraplatin is active in lung, ovarian and prostate cancer, and appears to have good efficacy in combination with radiation for lung and head and neck cancer. Preclinical data suggest it may also be effective for the treatment of certain cisplatin-refractory tumors. A large, randomized Phase III trial is currently evaluating Satraplatin in combination with prednisone for the treatment of patients with hormone-refractory prostate cancer whose disease has progressed following prior systemic therapy. Positive results from this trial would support regulatory approval for Satraplatin for this indication. The availability of an active oral platinum agent, such as Satraplatin, with few of the serious toxicities associated with traditional intravenous platinum compounds makes Satraplatin an alternative to other platinum agents and a new treatment option in the oncologist's armamentarium.
Clinical and pharmacokinetic evaluation of Satraplatin
Expert Opin Drug Metab Toxicol 2012 Jan;8(1):103-11.PMID:22098065DOI:10.1517/17425255.2012.636352.
Introduction: The toxicities of cisplatin, that is, nephrotoxicity, neurotoxicity and emesis, provided the impetus for the development of more tolerable platinum analogs. Satraplatin is an investigational third-generation orally available lipophilic platinum, which has demonstrated safety and antitumor activity in multiple settings. Areas covered: The clinical activity of Satraplatin in metastatic castrate-resistant prostate cancer (mCRPC), breast, lung and other advanced solid tumors is discussed with a focus on its pharmacokinetic properties. The article was formulated using publications found through PubMed search in addition to presentations given at major conferences. Expert opinion: Satraplatin was associated with dose-limiting myelosuppression, but no significant ototoxicity, neurotoxicity or nephrotoxicity. Despite the activity of Satraplatin in mCRPC, survival was not extended in an unselected population included in a Phase III trial. While further development of Satraplatin in large Phase III trials is not planned at this time, efforts are ongoing to develop tailored therapy in mCRPC based on excision repair cross-complementing group 1 expression or BRCAness. Moreover, based on potentially better central nervous system penetration due to lipophilicity, evaluation in patients with brain tumors is ongoing. Given the favorable toxicity profile and convenient oral administration, Satraplatin may warrant development in settings that preclude cisplatin, for example, underlying renal dysfunction, elderly age and poor performance status.