CN106902106B - Application of the pan-HDAC inhibitor in the drug of preparation treatment uveal - Google Patents
Application of the pan-HDAC inhibitor in the drug of preparation treatment uveal Download PDFInfo
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- CN106902106B CN106902106B CN201710192859.0A CN201710192859A CN106902106B CN 106902106 B CN106902106 B CN 106902106B CN 201710192859 A CN201710192859 A CN 201710192859A CN 106902106 B CN106902106 B CN 106902106B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
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Abstract
The present invention provides a kind of application of pan-HDAC inhibitor in the drug of preparation treatment grape tumor melanoma.The pan-HDAC inhibitor is PCI-24781, molecular formula C21H23N3O5, molecular structural formula is shown in formula I:Present invention firstly discovers that PCI-24781 (Abexinostat) can significantly inhibit uveal melanoma cells growth, and drug effectiveness increases as concentration increases.It is intended that the clinical treatment of uveal provides new therapeutic agent, raising treatment validity extends patient's service life, improves life quality for the invention.The present invention is unprecedented to have opened up a new field.
Description
Technical field
The present invention relates to medical domains more particularly to pan-HDAC inhibitor in the medicine for preparing treatment uveal
Application in object.
Background technique
Uveal (Uveal melanoma, UM) is a kind of specific type of melanoma, originates from eye Portugal
Grape film layer.UM is the adult most common primary intraocular malignant, wherein most of is mela-noma of choroid.UM occurs logical
It is often simple eye, single stove, eyes occur or the same case that multifocal tumour intraocularly occurs is very rare.UM can not only cause
Patient's vision is lost, and seriously threatens patient vitals.UM mainly through hematogenous metastasis, has half patient that DISTANT METASTASES IN can occur,
Mainly it is transferred to liver.It is fatal usually within 1 year once diagnosis is established, because clinic is not treated effectively at present
Method.Even extracing before not having explicitly transfer and suffering from eye eyeball, 5 annual death rates still have 17%~53%.Closely
The disease incidence of melanoma shows a increasing trend over year, and annual growth is about 3~5%, has become clinically disease incidence and increases most
One of fast malignant tumour.Currently, lacking effective drug therapy for the tumour.PCI-24781 (Abexinostat) is one
The novel pan-HDAC inhibitor of kind, so far still without PCI-24781 (Abexinostat) in uveal
The report of application, it is unclear to the curative effect and mechanism of action of uveal.
Summary of the invention
In order to overcome the above-mentioned deficiencies of the prior art, the present invention provides a kind of pan-HDAC inhibitor treats Portugal in preparation
Application in the drug of grape film melanoma.The pan-HDAC inhibitor is PCI-24781, molecular formula C21H23N3O5,
Molecular structural formula is shown in formula I:
Preferably, PCI-24781 can effectively inhibit the growth of uveal melanoma cells, effect of drugs is with dense
Degree increases and increases.
Compared with prior art, beneficial effects of the present invention are as follows:
Present invention firstly discovers that PCI-24781 (Abexinostat) can significantly inhibit uveal melanoma cells life
It is long, and drug effectiveness increases as concentration increases.The invention is it is intended that the clinical treatment of uveal provides
New therapeutic agent improves treatment validity, extends patient's service life, improves life quality.The unprecedented developing of the present invention
PCI-24781 (Abexinostat) is used for a frontier of oncotherapy.(there is this medicine grinding in other tumours
Study carefully report, it is not known that whether can use this unprecedented word)
Detailed description of the invention:
Fig. 1 is the curve graph of the median lethal dose of OCM1 and OM431 in the embodiment of the present invention.
Fig. 2 is plate clone experimental result picture in the embodiment of the present invention.
Fig. 3 is cell proliferation experiment result figure in the embodiment of the present invention.
Specific embodiment
The present invention is further described below with reference to specific embodiment, to better understand the invention.
Pan-HDAC inhibitor of the invention is PCI-24781, molecular formula C21H23N3O5, No. CAS: 783355-60-
2/783356-67-2 (HCL) molecular weight 397.43.Molecular structural formula is shown in formula I:
Embodiment 1
IC50 measurement experiment
Experimental material: PCI-24781 (Abexinostat) is purchased from Selleck (China), cell-title glo kit
Purchased from Promega (U.S.)
Experimental procedure: OCM1 and OM431 cell inoculation trains liquid in 384 orifice plates, 2500, every hole cell, 50ul, if 10
PCI-24781 (Abexinostat) is added in concentration gradient, and 37 DEG C, after 5%CO2 cultivates 72h, cell-title glo examination is added
Agent is incubated at room temperature 10 minutes, upper machine testing, calculates IC50, i.e. median lethal dose according to the experimental result measured.Experimental result is shown in
Shown in Fig. 1.
Embodiment 2
Plate clone experiment
Experimental procedure: OCM1 and OM431 cell inoculation is in 6 orifice plates, and 1000, every hole cell, 2ml trains liquid, if 5 concentration
PCI-24781 (Abexinostat) is added in gradient, and 37 DEG C, after 5%CO2 is cultivated 7 days, violet staining, experimental result is shown in Fig. 2
It is shown.It can be seen that PCI-24781 (Abexinostat) inhibits the proliferation of uveal melanoma cells, and be in concentration dependence.
Embodiment 3:
Cell proliferation experiment (CCK8)
Experimental material: CCK8 is purchased from Japanese colleague's chemistry
OCM1 and OM431 cell inoculation trains liquid, 10umol PCI-24781 in 96 orifice plates, 5000, every hole cell, 100ul
(Abexinostat), 37 DEG C, 5%CO2 culture, respectively at 0h, for 24 hours, 10ul CCK8 is added in 48h, 72h, continues 37 DEG C of incubations
4h, upper machine survey absorbance value, as a result as shown in Figure 3.It can be seen that PCI-24781 (Abexinostat) can significantly inhibit uvea
The proliferation of melanoma cells.
Present invention firstly discovers that PCI-24781 (Abexinostat) can significantly inhibit uveal melanoma cells life
It is long, and drug effectiveness increases as concentration increases.The invention is it is intended that the clinical treatment of uveal provides
New therapeutic agent improves treatment validity, extends patient's service life, improves life quality.The unprecedented developing of the present invention
One new field.
Specific embodiments of the present invention are described in detail above, but it is merely an example, the present invention is simultaneously unlimited
It is formed on particular embodiments described above.To those skilled in the art, any couple of present invention carries out equivalent modifications and
Substitution is also all among scope of the invention.Therefore, without departing from the spirit and scope of the invention made by equal transformation and
Modification, all should be contained within the scope of the invention.
Claims (2)
1. a kind of application of pan-HDAC inhibitor in the drug of preparation treatment uveal, which is characterized in that institute
The pan-HDAC inhibitor stated is PCI-24781, molecular formula C21H23N3O5, molecular structural formula is shown in formula I:
2. pan-HDAC inhibitor according to claim 1 answering in the drug of preparation treatment uveal
With, which is characterized in that the drug effect increases as concentration increases.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710192859.0A CN106902106B (en) | 2017-03-28 | 2017-03-28 | Application of the pan-HDAC inhibitor in the drug of preparation treatment uveal |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710192859.0A CN106902106B (en) | 2017-03-28 | 2017-03-28 | Application of the pan-HDAC inhibitor in the drug of preparation treatment uveal |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106902106A CN106902106A (en) | 2017-06-30 |
| CN106902106B true CN106902106B (en) | 2019-06-21 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201710192859.0A Active CN106902106B (en) | 2017-03-28 | 2017-03-28 | Application of the pan-HDAC inhibitor in the drug of preparation treatment uveal |
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Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB201808500D0 (en) | 2018-05-23 | 2018-07-11 | Ditesan Ltd | Virus and virus use |
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2017
- 2017-03-28 CN CN201710192859.0A patent/CN106902106B/en active Active
Non-Patent Citations (2)
| Title |
|---|
| Histone Deacetylase Inhibitors Induce Growth Arrest and Differentiation in Uveal Melanoma;Solange Landreville et al;《Clin Cancer Res》;20120115;第18卷(第2期);408-416 * |
| Time dependent modulation of tumor radiosensitivity by a pan HDAC inhibitor: abexinostat;Sofia Rivera et al.;《Oncotarget》;20170125;第8卷(第34期);56210-56227 * |
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| CN106902106A (en) | 2017-06-30 |
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