Phosphaplatin compounds as therapeutic agents for treatment of bone blood cancers

A compound and blood cancer technology, applied in the direction of active ingredients of phosphorus compounds, drug combination, drug delivery, etc.

Active Publication Date: 2019-10-25
PHOSPLATIN THERAPEUTICS LLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Combined with the wide variety of bone cancer types, this requirement makes the development of bone cancer therapies a challenging task

Method used

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  • Phosphaplatin compounds as therapeutic agents for treatment of bone blood cancers
  • Phosphaplatin compounds as therapeutic agents for treatment of bone blood cancers
  • Phosphaplatin compounds as therapeutic agents for treatment of bone blood cancers

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0080] Determination of R,R-pyrodach-2 against multiple myeloma cell lines

[0081] The compound trans-(R,R)-1,2-cyclohexanediamine-(dihydropyrophosphate)platinum(II) (“R,R”) was tested on two multiple myeloma cell lines RPMI 8226 and MM1R -pyrodach-2"). IC50 values ​​of 2.90 uM and 2.78 uM were found for R,R-pyrodach-2 against the cell lines RPMI 8226 and MM1R, respectively, indicating the potency and activity of the compounds.

example 2

[0083] Detection of R,R-pyrodach-2 in Multiple Myeloma Mouse Model

[0084] background

[0085] Trans-pododach-2 compounds were tested on multiple myeloma mouse models, specifically Vk*MYC mice, which were reported to be reliable predictors of clinical activity of drugs in untreated and relapsed MM Preclinical models (Chesi, M. et al., "Cancer Cell", 2008, 23, 167-180; Chesi, M. et al., "Blood", 2012, 120(2): 376-385 ). Additionally, trans-pyrodach-2 compounds were detected in mice transplanted with the more aggressive bortezomib-resistant Vk12598 cell line and the multidrug-resistant Vk12653 cell line, both of which were derived from Vk*MYC mice were generated.

[0086] Materials and methods

[0087] Neonatal Vk*MYC mice were grown to one year or more, and peak M levels were monitored. After the concentration of the major M peak reaches a level between about 10 g / L and about 70 g / L (estimated by densitometry, comparing M peak to albumin), mice are candidates for initia...

example 3

[0095] Determination of Platinum Distribution in R,R-pyrodach-2 Treated Mice

[0096] Materials and methods

[0097] Five CD-1 mice were given (R,R)- pyrodach -2, and vehicle (phosphate buffered saline) was administered to another mouse. After administration, the (R,R)- pyrodach -2 treated mice were euthanized, and control mice were euthanized 45 minutes after dosing. Subsequently, the cadavers were snap-frozen at -70°C. Slides of whole-body sagittal cross-sections of control 45-minute and 24-hour mice were prepared. Then, the slide was scanned using Laser Ablation Inductively Coupled Plasma Mass Spectrometry (Laser Ablation Inductively Coupled Plasma Mass Spectrometry, LA-ICP-MS) to obtain the Pt((R,R)- pyrodach -2) the concentration of atomic components). Additional slides were prepared from adjacent locations and stained with hematoxylin & eosin (H&E) to map Pt signals to different organs and tissues.

[0098] result

[0099] It was observed that in processed s...

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PUM

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Abstract

Use of (pyrophosphato)platinum(II) or (pyrophosphato)platinum(IV) complexes (''phosphaplatin compounds''), especially (R,R)-l,2-cyclohexanediamine-(dihydrogen pyrophosphato)platinum(II) (or ''PT-112''), as therapeutic agents for treatment of bone and blood cancers, or cancers that metastasize to bones, and methods thereof, are disclosed.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Application No. 62 / 443,416, filed January 6, 2017, which is hereby incorporated by reference in its entirety. technical field [0003] The invention relates to the use and method of a phosphoplatin compound as a therapeutic agent for treating bone cancer or blood cancer. Background technique [0004] Bone is composed of osteoid (hard), cartilage (tough and elastic), and fibrous (filamentous) tissue, as well as elements of bone marrow. Bone cancer can start in any bone and any type of bone tissue in the body. If caught early, bone cancer can be treated with surgery to remove the tumor and cancer cells, especially if the tumor and cancer cells have not spread and can be removed cleanly, which would be ideal. More commonly, treatment requires a combination of surgery and other treatments such as stem cell transplant, chemotherapy, radiation ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/66A61K33/243A61P35/00C01C1/02
CPCA61P35/00A61K31/7135A61P35/04A61K33/243A61K31/6615A61K33/24A61K45/06A61P35/02A61K2300/00A61K9/0019A61K31/555
Inventor M·普赖斯T·埃姆斯
Owner PHOSPLATIN THERAPEUTICS LLC
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