吡铂(Picoplatin) - 药物靶点：DNA_专利_临床

概要

基本信息

药物类型

小分子化药

别名

(SP-4-3)-Amminedichloro(2-methylpyridine)platinium、Picoplatin (INN/USAN/BAN)

+ [8]

靶点

DNA

作用机制

DNA抑制剂(DNA抑制剂)、DNA烷化剂

治疗领域

肿瘤呼吸系统疾病消化系统疾病+ [3]

在研适应症-

非在研适应症

晚期恶性实体瘤膀胱癌乳腺癌+ [8]

原研机构

AnorMED, Inc.

在研机构-

非在研机构

Poniard Pharmaceuticals, Inc.

AnorMED, Inc.

最高研发阶段终止临床3期

首次获批日期-

最高研发阶段(中国)终止

特殊审评孤儿药 (美国)

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结构

分子式C6H10Cl2N2Pt

InChIKeyIIMIOEBMYPRQGU-UHFFFAOYSA-L

CAS号181630-15-9

关联

10

项与吡铂相关的临床试验

EUCTR2007-000528-42-HU / Not yet recruitingN/A

A Randomized, Controlled Phase III Trial of Picoplatin and Best Supportive Care (BSC) versus BSC Alone in Patients with Small Cell Lung Cancer (SCLC), Refractory or Progressive within Six Months of Completing First-Line, Platinum-Containing Chemotherapy

开始日期2008-08-08

申办/合作机构

Poniard Pharmaceuticals, Inc.

EUCTR2007-000528-42-BG / Not yet recruitingN/A

A Randomized, Controlled Phase III Trial of Picoplatin and Best Supportive Care (BSC) versus BSC Alone in Patients with Small Cell Lung Cancer (SCLC), Refractory or Progressive within Six Months of Completing First-Line, Platinum-Containing Chemotherapy

开始日期2008-07-17

申办/合作机构

Poniard Pharmaceuticals, Inc.

NCT00710697 / Unknown status临床1期

A Phase 1 Study of Picoplatin in Subjects With Advanced Non-Hematological Malignancies With Emphasis on Cardiac Repolarization

The purpose of this study is to investigate what effects, if any, picoplatin has on the heart rhythm.

开始日期2008-06-01

申办/合作机构

Poniard Pharmaceuticals, Inc.

100 项与吡铂相关的临床结果

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100 项与吡铂相关的转化医学

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100 项与吡铂相关的专利（医药）

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83

项与吡铂相关的文献（医药）

2024-12-01·Biochemical and Biophysical Research Communications

Quantum mechanical approaches and molecular docking studies of platinum based anticancer drugs Satraplatin and picoplatin structures

Article

作者: Sahadevan, Madhavi ; Subramanian, Karunagaran ; Sundaram, Mullainathan

The structures of the anticancer drug compounds satraplatin and picoplatin are optimized, and theoretical studies done by Density Functional Theory (DFT) to investigate the optical properties, global chemical descriptors, and band gap were calculated using the obtained Frontier molecular orbital values. The theoretically obtained data of the platinum drugs found to possess low energy gap values and low chemical hardness with high chemical softness describe that the compounds are chemically stable and most reactive. Using the molecular docking process, the binding mechanisms of the satraplatin and picoplatin drugs with cancer DNA structures were studied, and the results were analyzed. For the two drug compounds examined, satraplatin has shown the least binding energies at -5.06kcal/mol compared to picoplatin at -2.69 kcal/mol, and conformations with root mean square deviation (RMSD) values by DNA structures are less than or equal to 2.00 Å in targeting the specific DNA target residues of the reference bound ligand. The grid box was generated using the selective grid parameters using the Autodock 4.2 program. The drug molecules found to have the least binding energy value with the lowest inhibition constant implicate the good docking score towards the DNA structure by the docking studies. DFT studies also show good structural properties and chemical reactivity. From the obtained results, satraplatin and picoplatin were found to have good chemical descriptors and good binding affinity and are best suited for biological molecular targets.

2024-11-01·Carbohydrate Research

Picoplatin (II)-loaded chitosan nanocomposites as effective drug delivery systems: Preparation, mechanistic investigation of BSA/5-GMP/GSH binding and biological evaluations

Article

作者: Ahmed, Noha M ; Elmehasseb, Ibrahim M. ; Ibrahim, Mohamed M. ; Ahmed, Noha M. ; Shaban, Shaban Y ; Elmehasseb, Ibrahim M ; Shaban, Shaban Y. ; Ibrahim, Mohamed M

The goal of the current study is to improve the characteristics and bioavailability of the drug picoplatin (PPt) by encapsulating it in chitosan nanoparticles (CS NPs) which allows for the targeted delivery of cytotoxic cargo to cancerous tissue, reducing toxic side effects and raising the therapeutic index. When picoplatin was delivered into the CS, it was able to produce a complex with CS (PPt@CS NPs) that had an appropriate particle size of 275 ± 10 nm, a reasonably low PDI of 0.15 ± 0.05, and high stability (ζ = -22.1 ± 0.3 mV). Since almost all pharmaceuticals work by binding to specific proteins or DNA, the in vitro binding mechanism and affinity of bovine serum albumin (BSA), low molecular building units of nucleic acids (5-GMP), and Glutathione (GSH) (considering that cisplatin resistance could be due to a reaction between cisplatin and GSH) to PPt and PPt@CS NPs were examined using stopped-flow and other spectroscopic approaches. Through two reversible processes, a rapid second-order binding followed by a slower first-order isomerization reaction, and a static quenching mechanism, PPt and PPt@CS NPs bind to BSA with relative reactivity of around (PPt)/(PPt@CS NPs) = 1/2.5. The 5-GMP interaction studies demonstrated that, in addition to changing the binding mechanism, PPt's encapsulation in CS increases its rate of reaction through coordination affinity. PPt interacted with 5-GMP via two reversible processes, a rapid second-order binding to phosphate followed by a slower first-order migration to the N7 of pyrimidine moiety. PPt@CS NPs showed weaker binding to GSH compared to PPt and hence PPt@CS NPs exhibits a lower resistance factor. It was also found that the in vitro drug release of PPt@CS NPs in PBS at pH 7.4 was steady, releasing 30 % of the PPt in just 5 h. Nonetheless, 75 % of the release in a pH 5.4 solution containing 10 mM GSH-a solution that mimics the tumor microenvironment-shows that the PPt@CS NPs system is sensitive to GSH and specifically targets malignant tissue. The encapsulation of PPt in CS complex maintained its anticancer activity, as shown by an in vitro cell-survival assay on HepG2 cancer cell lines and also cleavage efficiency toward the minor groove of pBR322 DNA via the hydrolytic way. These findings collectively suggested that inclusion PPt in CS would be an effective strategy to formulate a novel picoplatin formulation intended for use as targeted anticancer treatment.

2023-01-01·Current pharmaceutical design

From Basics of Coordination Chemistry to Understanding Cisplatin-analogue Pt Drugs.

Article

作者: Yamamoto, Yuma ; Kostova, Irena ; Tsvetkova, Dobrina ; Nakane, Daisuke ; Akitsu, Takashiro

BACKGROUNDCisplatin, a platinum complex discovered by Rosenberg in 1969, has long been known as the first metal-based anticancer agent. Since then, various similar derivatives of cisplatin have been investigated for pharmacological activity, and the approved complexes have been applied as drugs.OBJECTIVESThe aims of the current study are: 1) to summarize the advantages and dose-limiting effects of the approved and unapproved chemotherapy platinum cytostatics, 2) to develop new strategies for the development of platinum anticancer drugs, and 3) to clarify the important factors for the mechanism of action of platinum complexes.METHODSA search was conducted in the literature databases, and the obtained information was summarized and analyzed.RESULTSMyelosuppression is the main dose-limiting effect and the reason for the disapproval of platinum complexes, such as picoplatin, enloplatin, miboplatin, sebriplatin, zeniplatin, spiroplatin, iproplatin, and ormaplatin. From the basic point of view of inorganic coordination chemistry, such as theoretical calculations, crystal structures of model complexes, docking structures with nucleic acid molecules, spectroscopy, and biological aspects, the importance of physicochemical properties of inorganic platinum complexes for their mechanism of action has been indicated. Spectroscopic methods, such as FTIR, NMR, X-ray crystal structure analysis, and fluorescence microscopy, are important for the investigation of the conformational changes in the binding of platinum complexes and DNA.CONCLUSIONIn the development of platinum complexes, strong anti-cancer drug activity, low toxicity, and resistance can be obtained by the application of polynuclear platinum agents, complexes with targeted activity, and nanoparticle formulations. Electronic structure, stereochemical, and thermodynamic properties are essential for understanding the reaction mechanism of platinum complexes.

100 项与吡铂相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D08968	吡铂	-	DB04874

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
去势抵抗性前列腺癌	临床3期	俄罗斯	Poniard Pharmaceuticals, Inc.	2006-06-01
转移性结直肠癌	临床3期	俄罗斯	Poniard Pharmaceuticals, Inc.	2006-04-01
结直肠癌	临床3期	俄罗斯	Poniard Pharmaceuticals, Inc.	-
结直肠癌	临床3期	俄罗斯	Poniard Pharmaceuticals, Inc.	-
卵巢癌	临床3期	欧洲	Poniard Pharmaceuticals, Inc.	-
卵巢癌	临床3期	欧洲	Poniard Pharmaceuticals, Inc.	-
前列腺癌	临床3期	俄罗斯	Poniard Pharmaceuticals, Inc.	-
前列腺癌	临床3期	俄罗斯	Poniard Pharmaceuticals, Inc.	-
小细胞肺癌	临床3期	-	AnorMED, Inc.	-
小细胞肺癌	临床3期	-	AnorMED, Inc.	-

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


SPEAR (ASCO2010)	临床3期	小细胞肺癌	401	Picoplatin + BSC	(衊夢餘鬱鏇製餘顧構網) = 膚窪淵糧繭艱構顧齋選獵鏇窪廠鑰觸選鏇壓壓 (積窪艱艱網膚繭齋齋鑰, CI 19 ~ 25) 更多	积极	2010-05-20
SPEAR (ASCO2010)	临床3期	小细胞肺癌	401	picoplatin (BSC)	(衊夢餘鬱鏇製餘顧構網) = 憲膚鹹齋鏇遞壓窪淵觸獵鏇窪廠鑰觸選鏇壓壓 (積窪艱艱網膚繭齋齋鑰, CI 16 ~ 24) 更多	积极	2010-05-20
ASCO2009	临床2期	转移性去势抵抗性前列腺癌一线	32	Picoplatin + Docetaxel + Prednisone	(窪壓艱襯齋夢壓簾糧夢) = 衊範襯構觸憲淵積鏇餘鏇鹹鏇淵積鹹鏇齋築襯 (鹹淵鬱鏇窪顧範築憲艱 )	-	2009-05-20
ASCO2009	临床2期	结直肠癌一线	101	Picoplatin	(遞艱繭遞淵艱願壓構範) = Neurotoxicity was less frequent and less severe in the FOLPI arm compared to the FOLFOX arm 膚廠鬱簾齋觸鑰築鹹製 (廠壓遞憲淵簾艱遞願觸 )	-	2009-05-20
ASCO2009	临床2期	结直肠癌一线	101	modified FOLFOX-6 (FOLFOX)		-	2009-05-20
AACR2009	临床1期	晚期恶性实体瘤	-	IV picoplatin	艱膚顧積膚窪鬱壓鑰鹹(製壓淵衊獵顧壓衊簾觸) = 餘餘選憲廠餘廠衊遞選構蓋顧窪淵願顧鹽廠鹹 (膚齋範顧鏇構鏇齋遞廠, 23) 更多	-	2009-05-01
AACR2009	临床1期	晚期恶性实体瘤	-	Oral picoplatin	艱膚顧積膚窪鬱壓鑰鹹(製壓淵衊獵顧壓衊簾觸) = 廠窪糧積願衊憲築積觸構蓋顧窪淵願顧鹽廠鹹 (膚齋範顧鏇構鏇齋遞廠, 28) 更多	-	2009-05-01
ASCO2008	临床1期	晚期恶性实体瘤	-	Picoplatin	(鹽衊憲醖簾憲鬱餘艱蓋) = 壓鑰衊遞壓蓋選觸願夢壓鏇製簾夢餘選憲廠遞 (憲鹹鹹範糧壓餘淵製蓋 )	-	2008-05-20
ASCO2008	临床2期	转移性去势抵抗性前列腺癌	30	Picoplatin with docetaxel + prednisone	(夢糧鏇夢鬱觸範鬱醖夢) = 構夢積壓製鑰餘獵壓蓋膚蓋醖願鏇蓋窪衊顧淵 (壓獵蓋夢鹹獵選餘襯積 ) 更多	-	2008-05-20
ASCO2008	临床2期	结直肠癌一线	59	Picoplatin + 5-fluorouracil + leucovorin (FOLPI)	(製鹹願窪膚構壓積蓋壓) = 餘選鹽淵憲繭網遞糧築築顧遞窪構壓鏇餘製鹹 (蓋製範範繭鑰襯鏇網選 )	-	2008-05-20
ASCO2007	临床2期	小细胞肺癌二线	77	Picoplatin	(餘製築觸鹹餘艱蓋襯鹽) = 衊膚窪蓋範艱範觸蓋壓艱膚顧獵膚獵鏇繭壓構 (範鹹願襯顧窪簾壓憲選 ) 更多	-	2007-06-20
ASCO2007	临床1期	转移性结直肠癌	23	Picoplatin every 2 weeks	(鹹壓製願願憲廠蓋選衊) = 選糧蓋鏇餘積膚糧繭選齋醖淵艱憲餘顧網鏇製 (顧繭製觸窪廠遞鹹壓鏇 )	-	2007-06-20
ASCO2007	临床1期	转移性结直肠癌	23	Picoplatin every 4 weeks	(鹹壓製願願憲廠蓋選衊) = 簾簾獵鬱積齋艱遞築襯齋醖淵艱憲餘顧網鏇製 (顧繭製觸窪廠遞鹹壓鏇 )	-	2007-06-20
ASCO2007	临床1期	转移性去势抵抗性前列腺癌	16	Picoplatin + Docetaxel + Prednisone	(鹽願顧艱衊範選淵簾獵) = 築願窪積夢廠簾艱鑰夢選願蓋窪壓蓋鹽簾衊鹽 (夢繭繭鹹積夢鹹遞鹹築 ) 更多	-	2007-06-20