Delving into the Latest Updates on Picoplatin with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

(SP-4-3)-Amminedichloro(2-methylpyridine)platinium, Picoplatin (INN/USAN/BAN), AMD 473

+ [8]

Target

DNA

Mechanism

DNA inhibitors(DNA inhibitors), DNA alkylating agents

Therapeutic Areas

NeoplasmsRespiratory DiseasesDigestive System Disorders+ [3]

Active Indication-

Inactive Indication

Advanced Malignant Solid NeoplasmBladder CancerBreast Cancer+ [8]

Originator Organization

AnorMED, Inc.

Active Organization-

Inactive Organization

Poniard Pharmaceuticals, Inc.

AnorMED, Inc.

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

RegulationOrphan Drug (US)

The 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.

METHODS:

A search was conducted in the literature databases, and the obtained information was summarized and analyzed.

RESULTS:

Myelosuppression 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.

CONCLUSION:

In 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.

22 Nov 2022·ACS omega

Thermosensitive Liposomes Encapsulating Nedaplatin and Picoplatin Demonstrate Enhanced Cytotoxicity against Breast Cancer Cells

Article

Author: Shoeib, Tamer ; Fahmy, Sherif Ashraf ; Dayyih, Alice Abu ; El-Said Azzazy, Hassan Mohamed ; Preis, Eduard ; Bakowsky, Udo ; Alawak, Mohamed

Thermosensitive liposomes (TSL) have been used for localized temperature-responsive release of chemotherapeutics into solid cancers, with a minimum of one invention currently in clinical trials (phase III). In this study, TSL was designed using a lipid blend comprising 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(polyethylene glycol)-2000] (DSPE-PEG-2000) (molar ratio of 88:9:2.8:0.2). Either nedaplatin (ND) or p-sulfonatocalix[4]arene-nedaplatin was encapsulated in the aqueous inner layer of TSL to form (ND-TSL) or p-SC4-ND-TSL, respectively. The hydrophobic platinum-based drug picoplatin (P) was loaded into the external lipid bilayer of the TSL to develop P-TSL. The three nanosystems were studied in terms of size, PDI, surface charge, and on-shelf stability. Moreover, the entrapment efficiency (EE%) and release % at 37 and 40 °C were evaluated. In a 30 min in vitro release study, the maximum release of ND, p-SC4-ND, and picoplatin at 40 °C reached 74, 79, and 75%, respectively, compared to approximately 10% at 37 °C. This demonstrated temperature-triggered drug release from the TSL in all three developed systems. The designed TSL exhibited significant in vitro anticancer activity at 40 °C when tested on human mammary gland/breast adenocarcinoma cells (MDA-MB-231). The cytotoxicity of ND-TSL, p-SC4-ND-TSL, and P-TSL at 40 °C was approximately twice those observed at 37 °C. This study suggests that TSL is a promising nanoplatform for the temperature-triggered release of platinum-based drugs into cancer cells.

01 Jun 2019·Bioorganic & medicinal chemistry lettersQ4 · MEDICINE

Anticancer platinum(II) complexes bearing N-heterocycle rings

Q4 · MEDICINE

Review

Author: Facchetti, Giorgio ; Rimoldi, Isabella

Starting from the pioneering discovery of picoplatin and phenanthriplatin, many efforts were realized by different research groups in the synthesis of different platinum(II) complexes, bearing a N-heterocycle moiety active as anticancer agents in different types of solid tumors. This review deals in particular with both the bifunctional and monofunctional platinum drugs, not only in dichloride platinum(II) complexes, but also in recent advances in modern platinum structures, i.e. cationic ones. Both the in vitro and in vivo studies of these anticancer agents are taken into account, with a special consideration for aggressive and orphan in treatment tumors.

100 Deals associated with Picoplatin

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External Link

KEGG	Wiki	ATC	Drug Bank
D08968	Picoplatin	-	DB04874

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Small Cell Lung Cancer	Phase 3	AR	Poniard Pharmaceuticals, Inc.	01 Apr 2007
Small Cell Lung Cancer	Phase 3	BY	Poniard Pharmaceuticals, Inc.	01 Apr 2007
Small Cell Lung Cancer	Phase 3	BA	Poniard Pharmaceuticals, Inc.	01 Apr 2007
Small Cell Lung Cancer	Phase 3	BG	Poniard Pharmaceuticals, Inc.	01 Apr 2007
Small Cell Lung Cancer	Phase 3	CL	Poniard Pharmaceuticals, Inc.	01 Apr 2007
Small Cell Lung Cancer	Phase 3	HR	Poniard Pharmaceuticals, Inc.	01 Apr 2007
Small Cell Lung Cancer	Phase 3	HU	Poniard Pharmaceuticals, Inc.	01 Apr 2007
Small Cell Lung Cancer	Phase 3	IN	Poniard Pharmaceuticals, Inc.	01 Apr 2007
Small Cell Lung Cancer	Phase 3	LV	Poniard Pharmaceuticals, Inc.	01 Apr 2007
Small Cell Lung Cancer	Phase 3	ME	Poniard Pharmaceuticals, Inc.	01 Apr 2007

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


SPEAR (ASCO2010)	Phase 3	Small Cell Lung Cancer	401	Picoplatin + BSC	ynuzfabfrk(mugtgcryqv) = ebmcgejceh kynsmszhiu (zpdsonhgyo, CI 19 - 25) View more	Positive	20 May 2010
				picoplatin (BSC)	ynuzfabfrk(mugtgcryqv) = uijmozxofa kynsmszhiu (zpdsonhgyo, CI 16 - 24) View more
ASCO2009	Phase 2	Colorectal Cancer First line	101	Picoplatin	jziuddrcpw(aeafxwgtgq) = Neurotoxicity was less frequent and less severe in the FOLPI arm compared to the FOLFOX arm vbwrxlezsk (xuiccvkezl )	-	20 May 2009
				modified FOLFOX-6 (FOLFOX)
ASCO2009	Phase 2	Metastatic castration-resistant prostate cancer First line	32	Picoplatin + Docetaxel + Prednisone	mfcdmcdmyg(yxerqrqyzh) = djbhcfdzie qsikgozutx (itexxbkoya )	-	20 May 2009
AACR2009	Phase 1	Colorectal Cancer	73	Pico every 4 wks	tbxnjwxdnm(zchxlqbanx) = trotzbyvox khbjtcwuzt (djdirvdwhb )	-	01 May 2009
				Pico every 2 wks	wdqurpcfnf(zqelnpjrjw) = nkztieueqv kqrfqouize (sbairorugu )
AACR2009	Phase 1	Advanced Malignant Solid Neoplasm	-	IV picoplatin	ppncxcxvlq(yytqcdfebr) = bsxlrymvpq clsoovansz (ronxyubqfd, 23) View more	-	01 May 2009
				Oral picoplatin	ppncxcxvlq(yytqcdfebr) = vhhkkjrnfw clsoovansz (ronxyubqfd, 28) View more
ASCO2008	Phase 2	Metastatic castration-resistant prostate cancer	30	Picoplatin with docetaxel + prednisone	czxgnxajct(xgpuxsgqjn) = lgzbzxaupy digratvlhf (dtbjsmwbdq ) View more	-	20 May 2008
ASCO2008	Phase 1	Advanced Malignant Solid Neoplasm	-	Picoplatin	szmkzgqzsg(puugtddhye) = vuazucojbl sjoanzraoi (pjckdkkgkd )	-	20 May 2008
ASCO2008	Phase 2	Colorectal Cancer First line	59	Picoplatin + 5-fluorouracil + leucovorin (FOLPI)	mgbvjswhzy(tjhbwyiwzj) = hytfnnzffq ivnisuafjj (rwskxcybcv )	-	20 May 2008
ASCO2007	Phase 1	Metastatic castration-resistant prostate cancer	16	Picoplatin + Docetaxel + Prednisone	vepkrfdyyu(pqwgtqgrkb) = qfyhzvlyhu aiethcbzou (xwerwybgfj ) View more	-	20 Jun 2007
ASCO2007	Phase 1	Metastatic Colorectal Carcinoma	23	Picoplatin every 2 weeks	yhootajddb(peaaowrlsv) = xjicivbcpi mpdiuvhsmc (gpoomayaba )	-	20 Jun 2007
				Picoplatin every 4 weeks	yhootajddb(peaaowrlsv) = ykyupchdxl mpdiuvhsmc (gpoomayaba )