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

Action

inhibitors

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.

License Organization

AstraZeneca PLC

AnorMED, Inc.

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

RegulationOrphan Drug (United States)

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Structure/Sequence

Molecular FormulaC6H10Cl2N2Pt

InChIKeyIIMIOEBMYPRQGU-UHFFFAOYSA-L

CAS Registry181630-15-9

Picoplatin is a new platinum-based chemotherapy drug that has been studied in a variety of cancers. Phase 1 and 2 studies have demonstrated that picoplatin may be effective in patients whose cancer returns or does not improve after treatment with chemotherapy. In these studies, picoplatin was administered intravenously. A capsule containing picoplatin has been formulated. This study will investigate the activity of the oral capsule in humans. Participants with advanced solid tumors will be enrolled.

Start Date01 Apr 2007

Sponsor / Collaborator

Poniard Pharmaceuticals, Inc.

NCT00465491

/ Unknown statusPhase 3

A Randomized, Controlled Phase III Trial of Picoplatin and 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.

Picoplatin is a new type of platinum drug that has been investigated in several clinical trials, and may provide an improved safety profile over current treatment options. This study is designed to compare the efficacy and safety of picoplatin plus Best Supportive Care (BSC) with BSC alone. Best Supportive Care includes care and treatment to optimize the comfort of patients and their ability to function, as well as to minimize the side-effects of anti-cancer treatments.

Start Date01 Apr 2007

Sponsor / Collaborator

Poniard Pharmaceuticals, Inc.

100 Clinical Results associated with Picoplatin

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100 Translational Medicine associated with Picoplatin

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100 Patents (Medical) associated with Picoplatin

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78

Literatures (Medical) associated with Picoplatin

10 Feb 2025·INORGANIC CHEMISTRY

Exploring the Structure–Activity Relationships of Albumin-Targeted Picoplatin-Based Platinum(IV) Prodrugs

Article

Author: Adamova, Barbora ; Keppler, Bernhard K. ; Schueffl, Hemma ; Kastner, Alexander ; Berger, Walter ; Dijkstra, Martijn ; Baumfried, Oliver ; Kowol, Christian R. ; Heffeter, Petra

Platinum(II) complexes prevail as first-line treatment for many cancers but are associated with serious side effects and resistance development. Picoplatin emerged as a promising alternative to circumvent GSH-induced tumor resistance by introducing a bulky 2-picoline ligand. Although clinical studies were encouraging, picoplatin did not receive approval. Interestingly, the anticancer potential of prodrugs based on picoplatin is widely underexplored, and even less so the respective tumor-targeting approaches. We synthesized two new "hybrid" picoplatin(II) derivatives with an oxalate or cyclobutane dicarboxylate leaving group and their corresponding platinum(IV) prodrugs with an albumin-targeting maleimide moiety or a succinimide as reference. Picoplatin(II) and its derivatives indeed reacted much slower with GSH compared to the respective analogs cisplatin, carboplatin, or oxaliplatin. While PicoCarbo(IV) and PicoOxali(IV) were reduced slowly in the presence of ascorbic acid, picoplatin(IV) was extremely unstable. All three prodrugs were widely inactive in the MTT assays. The platinum(IV)-maleimide complexes rapidly bound to albumin with stable conjugates for >25 h. Albumin-binding resulted in elevated platinum plasma levels, prolonged blood circulation, and enhanced tumor accumulation of the prodrugs in mice bearing CT26 tumors. However, only maleimide-functionalized PicoCarbo(IV) and picoplatin(II) significantly inhibited tumor growth. One possible explanation is that for albumin-binding platinum(IV) prodrugs, the bulky 2-picoline moiety prevents sufficient activation/reduction to unlock their full anticancer potential.

01 Dec 2024·BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

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

Article

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

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.

01 Jun 2023·Current pharmaceutical design

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

Review

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

Background::

Cisplatin, 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.

Objectives::

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.

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	Argentina	Poniard Pharmaceuticals, Inc.	01 Apr 2007
Small Cell Lung Cancer	Phase 3	Belarus	Poniard Pharmaceuticals, Inc.	01 Apr 2007
Small Cell Lung Cancer	Phase 3	Bosnia and Herzegovina	Poniard Pharmaceuticals, Inc.	01 Apr 2007
Small Cell Lung Cancer	Phase 3	Bulgaria	Poniard Pharmaceuticals, Inc.	01 Apr 2007
Small Cell Lung Cancer	Phase 3	Chile	Poniard Pharmaceuticals, Inc.	01 Apr 2007
Small Cell Lung Cancer	Phase 3	Croatia	Poniard Pharmaceuticals, Inc.	01 Apr 2007
Small Cell Lung Cancer	Phase 3	Hungary	Poniard Pharmaceuticals, Inc.	01 Apr 2007
Small Cell Lung Cancer	Phase 3	India	Poniard Pharmaceuticals, Inc.	01 Apr 2007
Small Cell Lung Cancer	Phase 3	Latvia	Poniard Pharmaceuticals, Inc.	01 Apr 2007
Small Cell Lung Cancer	Phase 3	Montenegro	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


NCT00465491 (SPEAR, ASCO2010)	Phase 3	Small Cell Lung Cancer	401	Picoplatin + BSC	zjhyaxjvyr(dmqlbvugek) = kqditleoww yjbfhtbuzo (jcmbwbczur, CI 19 - 25) View more	Positive	20 May 2010
				picoplatin (BSC)	zjhyaxjvyr(dmqlbvugek) = vxvduedlhh yjbfhtbuzo (jcmbwbczur, CI 16 - 24) View more
ASCO2009	Phase 2	Colorectal Cancer First line	101	Picoplatin	ikxdptsjhy(giylpitpxl) = Neurotoxicity was less frequent and less severe in the FOLPI arm compared to the FOLFOX arm lwlooruwxm (drionuddlx )	-	20 May 2009
				modified FOLFOX-6 (FOLFOX)
ASCO2009	Phase 2	Metastatic castration-resistant prostate cancer First line	32	Picoplatin + Docetaxel + Prednisone	daahdexusk(eiyygmrkmm) = eszvkhisxk ncksgxuwpj (xfagrwtnad )	-	20 May 2009
AACR2009	Phase 1	Colorectal Cancer	73	Pico every 4 wks	vmmsafijdc(qohetqmxrv) = hytibimxdm zrcmtqgeaj (dpautiyiiy )	-	01 May 2009
				Pico every 2 wks	tzwenxhdtz(nqltrolivh) = fhtpcnaqer fndqoxjhic (pjsdvwrcuv )
AACR2009	Phase 1	-	-	IV picoplatin	nukywkjxhs(axxasowlxc) = orkjmfaxtk ufepnvkjai (ifqwzxqygr, 23) View more	-	01 May 2009
				Oral picoplatin	nukywkjxhs(axxasowlxc) = cabugbxlcn ufepnvkjai (ifqwzxqygr, 28) View more
ASCO2008	Phase 2	Colorectal Cancer First line	59	Picoplatin + 5-fluorouracil + leucovorin (FOLPI)	cdhejbbhpw(qccfmelhwj) = yvhzemxohq uthrsphkuy (hfrpkhufwj )	-	20 May 2008
ASCO2008	Phase 2	Metastatic castration-resistant prostate cancer	30	Picoplatin with docetaxel + prednisone	goqdjwsvny(gykrmpyilr) = exvbradoco implzknjoi (gbkhrnjzbe ) View more	-	20 May 2008
ASCO2008	Phase 1	Advanced Malignant Solid Neoplasm	-	Picoplatin	kkndcgugsm(unpjdzqrbt) = ghksjlfpzm fnukxrywhv (gvxgpprsyq )	-	20 May 2008
ASCO2007	Phase 1	Metastatic castration-resistant prostate cancer	16	Picoplatin + Docetaxel + Prednisone	wmyqurxhwy(ldneyjrgli) = lodboeeniu vjqgagydxh (rvtaxradvd ) View more	-	20 Jun 2007
ASCO2007	Phase 1	Metastatic Colorectal Carcinoma	23	Picoplatin every 2 weeks	meppqbwkkk(clalvtabtj) = pzdagsurjm wlgevrgvdv (ddqgjqcjni )	-	20 Jun 2007
				Picoplatin every 4 weeks	meppqbwkkk(clalvtabtj) = pahwgrdazz wlgevrgvdv (ddqgjqcjni )