CN110448557A - The new drug purposes of anticoagulant dabigatran etcxilate - Google Patents
The new drug purposes of anticoagulant dabigatran etcxilate Download PDFInfo
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- CN110448557A CN110448557A CN201910835039.8A CN201910835039A CN110448557A CN 110448557 A CN110448557 A CN 110448557A CN 201910835039 A CN201910835039 A CN 201910835039A CN 110448557 A CN110448557 A CN 110448557A
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- Prior art keywords
- dabigatran etcxilate
- cancer cell
- anticoagulant
- drug
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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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Public Health (AREA)
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- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
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- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Abstract
The invention discloses the new drug purposes of anticoagulant dabigatran etcxilate, the drug is used to inhibit the proliferation of breast cancer cell MCF-7, T47D and prostate gland cancer cell PC-3.It is for doing anticoagulant before dabigatran etcxilate, this drug of new discovery dabigatran etcxilate has anticancer therapeutic, has stronger inhibiting effect to breast cancer cell MCF-7, T47D and prostate gland cancer cell PC-3, can study for treating corresponding cancer in the present invention.
Description
Technical field
The present invention relates to anticancer drug technology related fields more particularly to the new drug purposes of anticoagulant dabigatran etcxilate.
Background technique
In sybyl-x2.0 software, with colchicin tubulin (PDB:1as0) for target, to from ZINC database
The FDA database of downloading carries out virtual screening experiment, and in the selection result, discovery marking Total_Score is 12.2486
ZINC03943279 and protein binding obtain preferably.ZINC03943279, that is, dabigatran etcxilate, the entitled Pradaxa of English, makees always
For anticoagulant, its anticancer activity is had not been reported.And micro-pipe is played an important role in cell mitogen process, is had become
The important target spot that antineoplastic is developed for researcher, then does tumor cell viability test experiments to dabigatran etcxilate, it is found that it is right
MCF-7, PC-3, T47D cancer cell have compared with strong rejection capability.Dabigatran etcxilate is measured to the activity IC half-suppressed of MCF-750For
4.761±0.6777(umol.L-1), to the activity IC half-suppressed of PC-350For 10.75 ± 1.032 (umol.L-1), to T47D's
IC living half-suppressed50For 16.67 ± 1.222 (umol.L-1)。
For this purpose, we have proposed the new drug purposes of anticoagulant dabigatran etcxilate.
Summary of the invention
The purpose of the present invention is to provide the new drug purposes of anticoagulant dabigatran etcxilate, have to cancer cell and make compared with high inhibition
With there is anticancer therapeutic.
For this purpose, it is an object of the invention to propose that anticoagulant dabigatran etcxilate is preparing the purposes in anticancer drug, institute
Drug is stated for inhibiting the proliferation of breast cancer cell MCF-7, T47D and prostate gland cancer cell PC-3, the dabigatran ester structure
Formula is shown in formula I:
Compared with prior art, the beneficial effects of the present invention are:
It is for doing anticoagulant before dabigatran etcxilate, this drug of new discovery dabigatran etcxilate has anti-in the present invention
Cancer curative effect has stronger inhibiting effect to breast cancer cell MCF-7, T47D and prostate gland cancer cell PC-3, can study for controlling
Treat corresponding cancer.
Detailed description of the invention
Fig. 1 is the structure of the new drug crystal structure of 1as0 on the way of anticoagulant dabigatran etcxilate proposed by the present invention
Figure；
Fig. 2 is that the new drug of anticoagulant dabigatran etcxilate proposed by the present invention uses the master of ZINC03943279 and 1sa0 on the way
Want amino acid action diagram；
Fig. 3 is the new drug C on the way of anticoagulant dabigatran etcxilate proposed by the present invention34H41N7O5To the medicine of PC-3 cell
The schematic diagram of object effect.
Specific embodiment
Following will be combined with the drawings in the embodiments of the present invention, and technical solution in the embodiment of the present invention carries out clear, complete
Site preparation description, it is clear that described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments.
Combined with specific embodiments below the present invention is made further to explain, purpose, which is only that, to be better understood in the present invention
Hold.
Referring to Fig.1-3, the invention also provides the new drug purposes of anticoagulant dabigatran etcxilate, and the drug is for inhibiting
The proliferation of breast cancer cell MCF-7, T47D and prostate gland cancer cell PC-3.
Wherein, dabigatran etcxilate structural formula is shown in formula I.
Wherein, scoring parameters are docked:
Wherein, the primary amino acid action diagram (as shown in Figure 2) of ZINC03943279 and 1sa0: the ASN101 of itself and albumen
Form hydrogen bondALA317Hydrogen bond is formed, so that the combination of ligand and ZINC03943279 are opposite steady
It is fixed.
Wherein, IC50Parameter:
Wherein, micro-pipe is played an important role in cell mitogen process, it has also become researcher develops antineoplastic
Important target spot carries out FDA database for target with colchicin tubulin (PDB:1as0) in sybyl-x2.0 software
Virtual screening maps to the ZINC03943279 fictionalized i.e. dabigatran etcxilate with Pymol, finds itself and 1as0 albumen
ASN101 forms hydrogen bondALA317Hydrogen bond is formed, hydrogen bond action is strong, combines closely with albumen.It reaches
Than adding group ester to be used as anticoagulant always, inhibiting effect is implicitly present in cancer cell for confirmation this drug of dabigatran etcxilate,
Cell experiment active testing is carried out；It was found that its having compared with strong rejection capability to MCF-7, PC-3, T47D cancer cell；Measure Da Bijia
Half-suppressed activity IC of group's ester to MCF-750For 4.761 ± 0.6777 (umol.L-1), to the activity IC half-suppressed of PC-350For
10.75±1.032(umol.L-1), to the IC living half-suppressed of T47D50For 16.67 ± 1.222 (umol.L-1)；MCF-7,T47D
For human breast cancer cell, PC-3 is Human Prostate Cancer Cells；Dabigatran etcxilate original is used as anticoagulant, is ratified to list by FDA,
By this research new discovery dabigatran etcxilate, this drug has new application, has to cancer cell and acts on compared with high inhibition, there is anticancer
Curative effect.
Referring to Fig. 3, C is tested34H41N7O5To the drug effect (0-20-30 μM/) of PC-3 cell, testing time are as follows: 0h,
For 24 hours and 48h, the result of test are as follows: drug effect is at concentration and Time Dependent.
The foregoing is only a preferred embodiment of the present invention, but scope of protection of the present invention is not limited thereto,
Anyone skilled in the art in the technical scope disclosed by the present invention, according to the technique and scheme of the present invention and its
Inventive concept is subject to equivalent substitution or change, should be covered by the protection scope of the present invention.
Claims (1)
1. anticoagulant dabigatran etcxilate shown in Formulas I is preparing the purposes in anticancer drug, which is characterized in that the drug is used for
Inhibit the proliferation of breast cancer cell MCF-7, T47D and prostate gland cancer cell PC-3,
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910835039.8A CN110448557A (en) | 2019-09-05 | 2019-09-05 | The new drug purposes of anticoagulant dabigatran etcxilate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910835039.8A CN110448557A (en) | 2019-09-05 | 2019-09-05 | The new drug purposes of anticoagulant dabigatran etcxilate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110448557A true CN110448557A (en) | 2019-11-15 |
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| CN201910835039.8A Pending CN110448557A (en) | 2019-09-05 | 2019-09-05 | The new drug purposes of anticoagulant dabigatran etcxilate |
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2734809A1 (en) * | 2008-08-19 | 2010-02-25 | Boehringer Ingelheim International Gmbh | Dabigatran in tumour therapy |
| CN103945845A (en) * | 2011-07-25 | 2014-07-23 | 第三专利投资有限两合公司 | Dabigatran-amidoxime acid esters as prodrugs and use thereof as pharmaceuticals |
| CN103998468A (en) * | 2011-11-03 | 2014-08-20 | 皮埃尔法布雷医药公司 | Antigen binding protein and its use as addressing product for the treatment cancer |
| CN104487441A (en) * | 2012-06-18 | 2015-04-01 | 普林斯匹亚生物制药公司 | Reversible covalent pyrrolo- or pyrazolopyrimidines useful for treatment of cancer and autoimmune diseases |
| US20150314017A1 (en) * | 2015-07-15 | 2015-11-05 | Suzhou M-Conj Biotech Co., Ltd | Disulfur bridge linkers for conjugation of a cell-binding molecule |
| WO2016024227A1 (en) * | 2014-08-11 | 2016-02-18 | Acerta Pharma B.V. | Btk inhibitors to treat solid tumors through modulation of the tumor microenvironment |
| CN109912683A (en) * | 2017-12-13 | 2019-06-21 | 杭州多禧生物科技有限公司 | A kind of cytotoxic molecule, conjugate and its preparation method and application |
-
2019
- 2019-09-05 CN CN201910835039.8A patent/CN110448557A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2734809A1 (en) * | 2008-08-19 | 2010-02-25 | Boehringer Ingelheim International Gmbh | Dabigatran in tumour therapy |
| CN103945845A (en) * | 2011-07-25 | 2014-07-23 | 第三专利投资有限两合公司 | Dabigatran-amidoxime acid esters as prodrugs and use thereof as pharmaceuticals |
| CN103998468A (en) * | 2011-11-03 | 2014-08-20 | 皮埃尔法布雷医药公司 | Antigen binding protein and its use as addressing product for the treatment cancer |
| CN104487441A (en) * | 2012-06-18 | 2015-04-01 | 普林斯匹亚生物制药公司 | Reversible covalent pyrrolo- or pyrazolopyrimidines useful for treatment of cancer and autoimmune diseases |
| WO2016024227A1 (en) * | 2014-08-11 | 2016-02-18 | Acerta Pharma B.V. | Btk inhibitors to treat solid tumors through modulation of the tumor microenvironment |
| US20150314017A1 (en) * | 2015-07-15 | 2015-11-05 | Suzhou M-Conj Biotech Co., Ltd | Disulfur bridge linkers for conjugation of a cell-binding molecule |
| CN109912683A (en) * | 2017-12-13 | 2019-06-21 | 杭州多禧生物科技有限公司 | A kind of cytotoxic molecule, conjugate and its preparation method and application |
Non-Patent Citations (7)
| Title |
|---|
| CASTLE J, ET AL: "PO-11 - Thrombin and cancer stem-like cells: in vitro support for breast cancer anticoagulation", 《THROMB RES》 * |
| DEFEO K，ET AL: "Use of dabigatran etexilate to reduce breast cancer progression", 《CANCER BIOL THER》 * |
| RYN J V，ET AL: "Dabigatran Etexilate : Pharmacology of the New, Oral Direct Thrombin Inhibitor", 《JAPANESE JOURNAL OF THROMBOSIS & HEMOSTASIS》 * |
| SONG S,ET AL: "First Reported Case of Hemopericardium Related to Dabigatran Use Reversed by New Antidote Idarucizumab", 《CASE REP CARDIOL》 * |
| 刘秋颖，等: "恶性肿瘤患者出现单纯凝血酶时间明显延长的原因探讨", 《检验医学》 * |
| 方英立，等: "肿瘤患者化疗期间抗凝治疗的监护点探讨", 《药品评价》 * |
| 陈冰: "达比加群酯治疗老年非瓣膜性心房颤动患者的凝血功能变化", 《中国医药指南》 * |
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Application publication date: 20191115 |