Miriplatin (SM-11355)
(Synonyms: 米铂,SM-11355) 目录号 : GC32886
Miriplatin (SM-11355) is a derivative of cisplatin containing myristates as a carrier ligand. It is a novel lipophilic platinum complex developed to treat hepatocellular carcinoma.DMSO is not recommended to dissolve platinum-based drugs, which can easily lead to drug inactivation.
Cas No.:141977-79-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | Aliquots of AH109A cells are plated into 24-well microplates. Following cell adherence (1 day), Lipiodol (LPD) alone and agents (Miriplatin, etc.) suspended in LPD are added to Falcon cell culture inserts, equipped with a 0.4-μm pore membrane on their bottom. After 7 days of incubation at 37°C in 5% CO2, the numbers of viable cells are examined using AlamarBlue. The IC50 value is defined as the concentration inhibiting cell growth by 50% compared with treatment with LPD alone. To examine platinum concentrations in the medium, agents suspended in LPD are added to Falcon cell culture inserts in wells containing the culture medium alone. The platinum concentrations are quantitatively analyzed by FAAS. Alternatively, aliquots of AH109A cells are plated into 96-well microplates. Following cell adherence (1 day), agents in aqueous solution are added. After 3 days of incubation at 37°C in 5% CO2, the numbers of viable cells are examined using AlamarBlue[2]. |
Animal experiment: | Rats[2]Rats bearing a tumor approximately 100-250 mm3 in area are randomly allocated into different treatment groups and a control group, each of which consists of seven rats. Tumor diameters are measured with calipers, and estimated tumor area is calculated by the formula: (smaller diameter) × (larger diameter). All agents (Miriplatin, etc.) suspended in Lipiodol (LPD) and LPD alone are injected into the hepatic artery of tumor-bearing rats at the volume of 0.02 mL/head. The therapeutic dose of each agent is defined in this study as follows: Miriplatin (400 μg/head, 20 mg/mL in LPD), cisplatin (400 μg/head, 20 mg/mL) and zinostatin stimalamer (20 μg/head, 1 mg/mL). After the intra-hepatic arterial administration, the gastroduodenal artery and abdomen are closed with uninterrupted sutures. The tumor growth rate (%) is calculated with the following formula: A7/A70 × 100, where A7 is the estimated tumor area at day 7 and A70 is the estimated tumor area at the initiation of the treatment (day 0). The systemic toxicity of the treatments is assessed in terms of changes in body weight during the experiments. These are calculated as (W7 − W70)/W70 × 100 where W7 is body weight at day 7 and W70 is body weight at day 0[2]. |
References: [1]. Kishimoto S, et al. Antitumor effects of a novel lipophilic platinum complex (SM-11355) against a slowly-growing rat hepatic tumor after intra-hepatic arterial administration. Biol Pharm Bull. 2000 Mar;23(3):344-8. | |
Miriplatin (SM-11355) is a derivative of cisplatin containing myristates as a carrier ligand. It is a novel lipophilic platinum complex developed to treat hepatocellular carcinoma.DMSO is not recommended to dissolve platinum-based drugs, which can easily lead to drug inactivation.
[1] Matthew D Hall, et al. Cancer Res. 2014 Jul 15;74(14):3913-22.
| Cas No. | 141977-79-9 | SDF | |
| 别名 | 米铂,SM-11355 | ||
| Canonical SMILES | NC1CCCCC1N.[O-]C(CCCCCCCCCCCCC)=O.[O-]C(CCCCCCCCCCCCC)=O.[Pt+2] | ||
| 分子式 | C34H68N2O4Pt | 分子量 | 764 |
| 溶解度 | DMF : < 1 mg/mL (insoluble) | 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 | 1.3089 mL | 6.5445 mL | 13.089 mL |
| 5 mM | 0.2618 mL | 1.3089 mL | 2.6178 mL |
| 10 mM | 0.1309 mL | 0.6545 mL | 1.3089 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。
A randomized phase II trial of intra-arterial chemotherapy using SM-11355 (Miriplatin) for hepatocellular carcinoma
Invest New Drugs 2012 Oct;30(5):2015-25.PMID:22187203DOI:10.1007/s10637-011-9776-4.
Background: SM-11355 is a platinum complex developed to treat hepatocellular carcinoma (HCC) via administration into the hepatic artery as a sustained-release suspension in iodized oil. We conducted a multicenter phase II trial in patients with HCC to evaluate the efficacy and safety of SM-11355, using a Zinostatin stimalamer suspension in iodized oil as a reference. Methods: Patients with unresectable HCC were randomized 2:1 to receive administration of the SM-11355 or Zinostatin stimalamer suspension into the hepatic artery. A second injection was given 4-12 weeks later. Efficacy was evaluated by CT 3 months after treatment and categorized as therapeutic effect (TE) V to I, where TE V was defined as disappearance or 100% necrosis of all treated tumors. Results: A total of 122 patients were evaluated for efficacy and toxicity (SM-11355, n = 83; Zinostatin stimalamer, n = 39). Baseline characteristics were similar in the two groups. The TE V rates were 26.5% (22/83) and 17.9% (7/39) in the SM-11355 and Zinostatin stimalamer groups, respectively. In the SM-11355 group,the most frequent drug-related adverse events (AEs) of ≥ grade 3 were elevated AST, elevated ALT, thrombocytopenia, and hyperbilirubinemia. The AEs with the largest difference between the two groups (SM-11355 vs. Zinostatin stimalamer) were hepatic vascular injury (0 vs. 48.4%) and eosinophilia (84.3 vs. 41.0%). The 2-year and 3-year survival rates were 75.9% vs. 70.3% and 58.4% vs. 48.7%, respectively. Conclusions: The results suggest that SM-11355 in iodized oil has similar efficacy to Zinostatin stimalamer and that repeated dosing of SM-11355 is possible without hepatic vascular injury in cases of relapse.
In vitro release of SM-11355, cis[((1R,2R)-1,2-cyclohexanediamine-N,N')bis(myristato)] platinum(II) suspended in lipiodol
Biol Pharm Bull 2000 May;23(5):637-40.PMID:10823679DOI:10.1248/bpb.23.637.
SM-11355, cis[((1R,2R)-1,2-cyclohexanediamine-N,N')bis(myristato)] platinum(II) is a lipophilic platinum complex. SM-11355 suspended in Lipiodol (SM-11355/Lipiodol) was previously shown to have antitumor effects against rat hepatic tumors after intra-arterial administration. In the present study, the in vitro release of platinum compounds from SM-11355/Lipiodol was examined. A test tube containing 10 ml of saline and 1 ml of SM-11355/Lipiodol was rotated at 5 rpm in a vertical orientation. The platinum concentration in saline gradually increased for 28 d. From HPLC analysis, cyclohexane-1,2-diamineplatinum(II) dichloride (DPC) and cyclohexane-1,2-diamineplatinum(II) chloroiodide (DPCI) were detected in the saline, and the sum of these two compounds was equivalent to the total platinum amount in the saline determined by atomic absorption spectrophotometry at days 21 and 28. DPC showed significant growth inhibitory activities, with IC50 values of 0.1-0.7 nmol/ml in rat hepatoma AH-109A cells and 5 human tumor cell lines, as effective as cisplatin. These findings suggest that SM-11355/Lipiodol exerts antitumor effects by releasing active platinum compounds, and that DPC is one of the candidates of the active compounds.
[Transcatheter arterial chemoembolization with a lipophilic platinum complex SM-11355(Miriplatin hydrate)--safety and efficacy in combination with embolizing agents]
Gan To Kagaku Ryoho 2010 Feb;37(2):271-5.PMID:20154484doi
SM-11355 is a cisplatin derivative with high affinity for iodized ethyl esters of fatty acids of poppyseed oil. Clinical trials have shown that SM-11355 is effective for treatment of hepatocellular carcinoma. Transcatheter arterial chemoembolization is commonly used in combination with embolizing agents, but concomitant use of SM-11355 and embolizing agents has not been evaluated in previous trials. In this study, the safety and efficacy of SM-11355 in combination with embolizing agents were investigated in 10 patients with hepatocellular carcinoma. An anti-tumor effect of TE4 was achieved in 4 of 9 patients and no serious adverse events were observed, indicating that this therapy can be used safely for hepatocellular carcinoma.
Transarterial chemoembolization with Miriplatin plus epirubicin in patients with hepatocellular carcinoma
Anticancer Res 2015 Jan;35(1):549-54.PMID:25550601doi
Aim: We aimed to evaluate the therapeutic efficacy of transcatheter arterial chemoembolization (TACE) using Miriplatin plus epirubicin in unresectable hepatocellular carcinoma (HCC). Patients and methods: The efficacy of TACE was evaluated by dynamic computed tomography (CT) or magnetic resonance imaging (MRI) three months after the procedure according to the Response Evaluation Criteria in Cancer Study Group of Japan. Adverse events (AEs), including clinical symptoms, hematological toxicities and blood chemistry toxicities, were assessed using Common Terminology Criteria Version 4.0. Results: Thirty patients with HCC received TACE with Miriplatin (Miriplatin group) and 29 patients received TACE with Miriplatin plus epirubicin (miriplatin-plus-epirubicin group). AEs, such as anorexia and neutropenia, were observed more frequently in the miriplatin-plus-epirubicin group than in the Miriplatin group (p=0.028 and 0.014, respectively). However, there was no significant difference in the incidence of these AEs (grade 3/4) between groups. The objective response rate (ORR), including the complete response (CR) and partial response (PR), was 76.7% in the Miriplatin group and 58.6% in the miriplatin-plus-epirubicin group (p=0.224). The median time to progression (TTP) in the Miriplatin group and the miriplatin-plus-epirubicin group was 8.2 and 6.1 months, respectively (p=0.123). Conclusion: Although TACE with Miriplatin plus epirubicin was safe and tolerable, no additional anti-tumor effects were observed compared to TACE with Miriplatin. Further analysis is required to refine the efficacy of TACE using Miriplatin plus epirubicin.
Antitumor effects of a novel lipophilic platinum complex (SM-11355) against a slowly-growing rat hepatic tumor after intra-hepatic arterial administration
Biol Pharm Bull 2000 Mar;23(3):344-8.PMID:10726891DOI:10.1248/bpb.23.344.
The antitumor effects of cis[((1R,2R)-1,2-cyclohexanediamine-N,N')bis(myristato)] platinum(II) (SM-11355) were evaluated in a rat hepatic tumor model, and were compared with those of cisplatin (CDDP). A novel slowly-growing rat hepatic tumor model was established by the successive transplantation of rat AH109A tumor into the liver. The drugs, which were suspended in Lipiodol, were administered into the proper hepatic artery of tumor-bearing rats. Tumor growth was suppressed in the group that received SM-11355 suspended in Lipiodol (SM-11355/Lipiodol). Mean tumor growth rates in the groups administered 20 microl of Lipiodol containing 0, 0.02, 0.04, 0.1, 0.2, or 0.4 mg of SM-11355 were 244, 86, 110, 81, 51, and 40%, respectively, 1 week after treatment. Those in the groups administered 20 microl of Lipiodol containing 0.1, 0.2, or 0.4 mg of CDDP were 240, 110, and 45%, respectively. In the groups administered 0.2 and 0.4 mg of SM-11355 or 0.4 mg of CDDP, massive necrosis was observed in the tumor tissue 1 week after drug administration, and the tumors disappeared 4 weeks after drug administration. Serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) levels were measured as markers of liver damage one day after the drug was administered into the hepatic artery of rats. The minimum toxic dose, which raised serum GOT and GPT levels significantly compared with Lipiodol alone, was 0.2 mg for SM-11355/Lipiodol and 0.1 mg for CDDP/Lipiodol, respectively. The results demonstrated that SM-11355/Lipiodol exerted antitumor activity at a dose that showed no hepatic toxicity in the rat model, but CDDP/Lipiodol did not.