cDPCP
目录号 : GC49307
A DNA-crosslinking agent
Cas No.:106343-59-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
cDPCP is a platinum-containing DNA-crosslinking agent.1 Unlike cisplatin or oxaliplatin , cDPCP forms monofunctional DNA adducts. It is transported into cells by organic cation transporter 1 (OCT1) and OCT2, inhibiting proliferation of MDCK cells expressing the human transporters with IC50 values of 8.1 and 1.5 µM, respectively. cDPCP inhibits RNA polymerase II-mediated transcription in a reporter assay using HeLa cells. It increases survival in murine S180 sarcoma and P388 leukemia models when administered at doses of 40 and 80 mg/kg, respectively.2
1.Lovejoy, K.S., Todd, R.C., Zhang, S., et al.cis-Diammine(pyridine)chloroplatinum(II), a monofunctional platinum(II) antitumor agent: Uptake, structure, function, and prospectsProc. Natl. Acad. Sci. USA105(26)8902-9807(2008) 2.Hollis, L.S., Amundsen, A.R., and Stern, E.W.Chemical and biological properties of a new series of cis-diammineplatinum(II) antitumor agents containing three nitrogen donors: cis-[Pt(NH3)2(N-donor)Cl]+J. Med. Chem.32128-136(1989)
| Cas No. | 106343-59-3 | SDF | |
| Canonical SMILES | [Cl-][Pt+2]([NH3])([N]1=CC=CC=C1)[NH3].[Cl-] | ||
| 分子式 | C5H11ClN3Pt·Cl | 分子量 | 379.2 |
| 溶解度 | DMSO: slightly soluble,Water: slightly soluble | 储存条件 | -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 | 2.6371 mL | 13.1857 mL | 26.3713 mL |
| 5 mM | 0.5274 mL | 2.6371 mL | 5.2743 mL |
| 10 mM | 0.2637 mL | 1.3186 mL | 2.6371 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。
Chemical and cellular investigations of trans-ammine-pyridine-dichlorido-platinum(II), the likely metabolite of the antitumor active cis-diammine-pyridine-chorido-platinum(II)
J Inorg Biochem 2013 Dec;129:15-22.PMID:24008133DOI:10.1016/j.jinorgbio.2013.07.040.
It has been proposed that the well-studied monofunctional platinum complex cis-[PtCl(NH3)2(py)](+) (cDPCP) forms DNA adducts similar to those of the trans platinum complex trans-[PtCl2(NH3)(py)] (ampyplatin, py=pyridine). Thus this latter could be the active form of cDPCP. Detailed studies on the mechanism of ampyplatin action were performed in this work. Results indicate that ampyplatin has significantly higher antiproliferative activity than cDPCP and is comparable to cisplatin. Cellular uptake experiments indicate that ampyplatin can be efficiently accumulated in A549 cancer cells. Binding of ampyplatin to DNA mainly produces monofunctional adducts; remarkably, these adducts can be recognized by the HMGB1 protein. Kinetic studies on the reaction with GMP indicate that the reactivity of ampyplatin is much lower than that of transplatin and is more similar to that of trans-[PtCl2{E-HN=C(Me)OMe}2] (trans-EE), a widely investigated antitumor active trans-oriented platinum complex. In addition, the hydrolysis of ampyplatin is significantly suppressed, whereas the hydrolysis of the mono-GMP adduct is highly enhanced. These results indicate that the mechanism of ampyplatin differs not only from that of antitumor inactive transplatin but also from that of antitumor active trans-EE and this could account for the remarkable activity of parent cDPCP.
cis-Diammine(pyridine)chloroplatinum(II), a monofunctional platinum(II) antitumor agent: Uptake, structure, function, and prospects
Proc Natl Acad Sci U S A 2008 Jul 1;105(26):8902-7.PMID:18579768DOI:10.1073/pnas.0803441105.
We have identified unique chemical and biological properties of a cationic monofunctional platinum(II) complex, cis-diammine(pyridine)chloroplatinum(II), cis-[Pt(NH(3))(2)(py)Cl](+) or cDPCP, a coordination compound previously identified to have significant anticancer activity in a mouse tumor model. This compound is an excellent substrate for organic cation transporters 1 and 2, also designated SLC22A1 and SLC22A2, respectively. These transporters are abundantly expressed in human colorectal cancers, where they mediate uptake of oxaliplatin, cis-[Pt(DACH)(oxalate)] (DACH = trans-R,R-1,2-diaminocyclohexane), an FDA-approved first-line therapy for colorectal cancer. Unlike oxaliplatin, however, cDPCP binds DNA monofunctionally, as revealed by an x-ray crystal structure of cis-{Pt(NH(3))(2)(py)}(2+) bound to the N7 atom of a single guanosine residue in a DNA dodecamer duplex. Although the quaternary structure resembles that of B-form DNA, there is a base-pair step to the 5' side of the Pt adduct with abnormally large shift and slide values, features characteristic of cisplatin intrastrand cross-links. cDPCP effectively blocks transcription from DNA templates carrying adducts of the complex, unlike DNA lesions of other monofunctional platinum(II) compounds like {Pt(dien)}(2+). cDPCP-DNA adducts are removed by the nucleotide excision repair apparatus, albeit much less efficiently than bifunctional platinum-DNA intrastrand cross-links. These exceptional characteristics indicate that cDPCP and related complexes merit consideration as therapeutic options for treating colorectal and other cancers bearing appropriate cation transporters.
Bio-inspired polymer envelopes around adenoviral vectors to reduce immunogenicity and improve in vivo kinetics
Acta Biomater 2016 Jan;30:94-105.PMID:26546972DOI:10.1016/j.actbio.2015.11.005.
Adenoviral vectors have attracted substantial interest for systemic tumor gene therapy, but further work is needed to reduce their immunogenicity and alter their biodistribution before they can be used in the clinic. Here we describe a bio-inspired, cleavable PEGylated β-cyclodextrin-polyethyleneimine conjugate (cDPCP) that spontaneously coats adenovirus in solution. This cleavable PEG coating reduces the innate and adaptive immunogenicity of adenovirus particles, as well as improves their biodistribution away from the liver and into the tumor. Insertion of a matrix metalloproteinase substrate sequence into the conjugate allows PEG cleavage at the tumor site, simultaneously reducing liver biodistribution and increasing transgene expression in tumors, thereby avoiding the "PEG dilemma". Cationic β-cyclodextrin-PEI not only provides electrostatic attraction to promote envelope attachment to the viral capsid, but it also improves vector internalization and transduction after PEG cleavage. These results suggest that cDPCP may help expand the use of adenoviral vectors in cancer gene therapy. Statement of significance: The synthesized β-cyclodextrin-PEI-MMP-cleavable-PEG polymer (cDPCP), held great potential for gene therapy when applied for adenovirus coating. The β-cyclodextrin-PEI provided a powerful electrostatic attraction to attach the whole polymer onto the viral capsid, while the MMPs-cleavable PEG reduced innate and adaptive immunogenicity and improved the biodistribution of adenovirus vectors due to the tumor-specific enzyme triggered PEG cleavage. More importantly, an ingenious cooperation between the two components could solve the PEG dilemma. The cDPCP/Ad complexes exhibited a comprehensive and valued profile to be a candidate vector for future tumor gene therapy, we believe the current investigation on this kind of biomaterial may be of particular interest to the readership of Acta biomaterialia.
Role of organic cation transporter 1, OCT1 in the pharmacokinetics and toxicity of cis-diammine(pyridine)chloroplatinum(II) and oxaliplatin in mice
Pharm Res 2011 Mar;28(3):610-25.PMID:21104302DOI:10.1007/s11095-010-0312-6.
Purpose: The goal of this study was to test the hypothesis that by controlling intracellular uptake, organic cation transporter 1, Oct1 is a key determinant of the disposition and toxicity of cis-diammine(pyridine)chloroplatinum(II)(cDPCP) and oxaliplatin. Methods: Pharmacokinetics, tissue accumulation and toxicity of cDPCP and oxaliplatin were compared between Oct1-/- and wild-type mice. Results: After intravenous administration, hepatic and intestinal accumulation of cDPCP was 2.7-fold and 3.9-fold greater in Oct1 wild-type mice (p < 0.001). Deletion of Oct1 resulted in a significantly decreased clearance (0.444 ± 0.0391 ml/min*kg versus 0.649 ± 0.0807 ml/min*kg in wild-type mice, p < 0.05) and volume distribution (1.90 ± 0.161 L/kg versus 3.37 ± 0.196 L/kg in wild-type mice, p < 0.001). Moreover, Oct1 deletion resulted in more severe off-target toxicities in CDPCP-treated mice. Histologic examination of the liver and measurements of liver function indicated that the level of hepatic toxicity was mild and reversible, but was more apparent in the wild-type mice. In contrast, the effect of Oct1 on the pharmacokinetics and toxicity of oxaliplatin in the mice was minimal. Conclusions: Our study suggests that Oct1 plays an important role in the pharmacokinetics, tissue distribution and toxicity of cDPCP, but not oxaliplatin.
Identification and Characterization of Approved Drugs and Drug-Like Compounds as Covalent Escherichia coli ClpP Inhibitors
Int J Mol Sci 2019 May 31;20(11):2686.PMID:31159170DOI:10.3390/ijms20112686.
The serine protease Caseinolytic protease subunit P (ClpP) plays an important role for protein homeostasis in bacteria and contributes to various developmental processes, as well as virulence. Therefore, ClpP is considered as a potential drug target in Gram-positive and Gram-negative bacteria. In this study, we utilized a biochemical assay to screen several small molecule libraries of approved and investigational drugs for Escherichia coli ClpP inhibitors. The approved drugs bortezomib, cefmetazole, cisplatin, as well as the investigational drug cDPCP, and the protease inhibitor 3,4-dichloroisocoumarin (3,4-DIC) emerged as ClpP inhibitors with IC50 values ranging between 0.04 and 31 µM. Compound profiling of the inhibitors revealed cefmetazole and cisplatin not to inhibit the serine protease bovine α-chymotrypsin, and for cefmetazole no cytotoxicity against three human cell lines was detected. Surface plasmon resonance studies demonstrated all novel ClpP inhibitors to bind covalently to ClpP. Investigation of the potential binding mode for cefmetazole using molecular docking suggested a dual covalent binding to Ser97 and Thr168. While only the antibiotic cefmetazole demonstrated an intrinsic antibacterial effect, cDPCP clearly delayed the bacterial growth recovery time upon chemically induced nitric oxide stress in a ClpP-dependent manner.