CN105412089A - Application of compound VS1 in preparation of anti-non-small cell lung cancer medicine - Google Patents
Application of compound VS1 in preparation of anti-non-small cell lung cancer medicine Download PDFInfo
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- CN105412089A CN105412089A CN201510837217.2A CN201510837217A CN105412089A CN 105412089 A CN105412089 A CN 105412089A CN 201510837217 A CN201510837217 A CN 201510837217A CN 105412089 A CN105412089 A CN 105412089A
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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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
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Abstract
The invention relates to new application of known compounds, in particular to application of a compound VS1 in preparation of an anti-non-small cell lung cancer medicine. It is verified that the compound has an obvious inhibitory effect on non-small cell lung cancer cell lines and can be used for preparation of the anti-non-small cell lung cancer medicine. According to the application, ERBB3 is used as an action target to obtain the compound having the obvious inhibitory effect on the non-small cell lung cancer cell lines through screening, and the application aims at providing a candidate lead compound for new drug research and development of the anti-non-small cell lung cancer medicine.
Description
Technical field
The present invention relates to the novelty teabag of known compound, be specifically related to the application of compound VS1 in the anti-non-small cell lung cancer drug of preparation.
Background technology
Natural product refers to that in constituent in animal, plant, insecticide, marine organisms and microbial body or its metabolite and humans and animals body, various endogenic chemical composition is referred to as natural product, wherein mainly comprises the naturally occurring chemical compositions such as protein, polypeptide, aminoacid, nucleic acid, various enzyme, monosaccharide, oligosaccharide, polysaccharide.Natural product has a wide range of applications in medicament research and development, and the typical medicaments now developed has quinine, morphine, digoxin, vincristine etc.From natural product, find bioactive ingredients and primer, with research and innovation medicine, be one of countries in the world new drug research scientist effective way of generally acknowledging, also obtained many achievements.
As the No.1 cancer killer in the whole world, the sickness rate of pulmonary carcinoma is in the world still in the trend continuing to rise in recent years, and this trend is especially obvious in China.The generation of pulmonary carcinoma, evolution are subject to the joint effect of h and E two aspect.But, because the genovariation in endogenous cause of ill is of a great variety, make to be difficult at present develop therapy or the medicine that effectively can treat pulmonary carcinoma that make new advances.
The up-to-date research be published on " NatureCommunications " in University of Michigan comprehensive rearch centre shows, gene unconventionality in pulmonary carcinoma is mainly distributed in two gene paths: Hippo path and neuregulin 1 (NRG1) path, do not find in the cancer that wherein NRG1 path is former.Drug research is carried out to NRG1 path, obtains targeting small-molecule drug by virtual screening, will novel drugs and the therapeutic scheme of studying treatment pulmonary carcinoma be contributed to.Due to synthesis Compound Phase ratio, natural product is similar to the endogenous metabolism product structure in human body, has better druggability, and academia generally believes that it can provide new hope for the treatment of tumor.Found that there is the natural quinoline compound 6-methyl kynurenic acid of antitumous effect such as, separate from Herba Ephedrae.
At present, the targeted drug based on ERBB family (EGFR isoform) specific molecular treatment nonsmall-cell lung cancer (Non-smallcelllungcancer, NSCLC) of tumor cell is studied and be widely used in clinical.Main targeted drug has two large classes: a class is micromolecular inhibitor, based on tyrosine kinase inhibitor (being called for short TKI).It enters in cell, and directly acts on the intracellular region of ERBB family, thus interference adenosine triphosphate (ATP) combines.Representational medicine is as gefitinib (Gefitinib) and Erlotinib (Erlotinib).Another kind of is monoclonal antibody, and it acts on extracellular region, and suppress the combination of part and ERBB family competitively, thus receptor is lost activity, affect the growth of cell, representational medicine is as Cetuximab (Cetuximab).But according to the existing literature survey to ERBB3 inhibitor, find that inhibitor is based on monoclonal antibody, chemical small molecule medicine is also mainly derived from synthesis.
Summary of the invention
(1) technical problem that will solve
Take ERBB3 as action target, obtain there is obvious inhibiting compound to Lines through screening, be intended to for the new drug development of anti-non-small cell lung cancer drug provides the lead compound of candidate.
(2) technical scheme
The present invention provide firstly the application of compound VS1 in the anti-non-small cell lung cancer drug of preparation, and described compound VS1 chemical structural formula is as follows:
The molecular weight of above-claimed cpd VS1 is 534.56194g/mol, and molecular formula is C
31h
26n
4o
5.
The present invention selects to buy above-claimed cpd VS1 and carries out Cell Biology Experiment, specifically select A549 Non-small cell lung carcinoma cell strain as subject cell system, MRC-5 people's normal chick embryo lung fibroblast cell line in contrast, cultivates by appropriate cell implantation concentrations regular growth culture method; CCK-8 reagent method measures the IC of medicine
50value and their antitumaous effect.Experimental result shows, above-claimed cpd has obvious inhibitory action to Non-small cell lung carcinoma cell line (A549).
Above-claimed cpd VS1 is the known compound that can commercially availablely buy, can purchased from eMolecules (http://www.emolecules.com) or IBScreenNP (http://www.ibscreen.com).
The present invention has obvious inhibitory action at the favorite outer discovery above-claimed cpd of actual R&D process for Non-small cell lung carcinoma cell line (A549), confirms that it can be effective to the anti-non-small cell lung cancer drug of preparation treatment.
Further, compound VS1 of the present invention can as the one in sole active agent in described anti-non-small cell lung cancer drug or active ingredient group, and other active component in described active ingredient group are chemical drugs or natural product.
Anti-non-small cell lung cancer drug of the present invention exists with the form of oral agents, cutaneous permeable agent or injection.
Preferably, anti-non-small cell lung cancer drug of the present invention can directly with compound VS1 of the present invention, or add pharmaceutically acceptable excipient further and be prepared into common dosage forms and be applied in anti-non-small cell lung cancer drug, desirable dosage form, as granule, tablet, capsule, injection etc., is specially those skilled in the art and grasps.
Further, anti-nonsmall-cell lung cancer of the present invention is preferably adenocarcinoma of lung.Through verification experimental verification, described compound VS1 is particularly remarkable for the medical active of adenocarcinoma of lung.
(3) beneficial effect
The present invention demonstrates the obvious inhibitory action of above-claimed cpd VS1 to Lines first, and can be used for preparing anti-non-small cell lung cancer drug, the new drug development for anti-non-small cell lung cancer drug provides the lead compound of candidate.
Accompanying drawing explanation
Fig. 1 is A549 cell inhibitory rate contrast schematic diagram;
Fig. 2 is MRC-5 cell inhibitory rate contrast schematic diagram.
Detailed description of the invention
Following examples for illustration of the present invention, but are not used for limiting the scope of the invention.
In following examples, compound VS1 comes from:
Tao Su is biochemical: (http://www.tsbiochem.com/);
Import is in IBScreenNP:(http: //www.ibscreen.com).
In addition, involved all test materials and reagent are by commercially available known materials of buying.
Embodiment 1
The present embodiment demonstrates compound VS1 of the present invention to the inhibitory action of Lines:
(1) select A549 and the MRC-5 attached cell of exponential phase, after trypsinization, be made into 5 × 10 respectively with the DMEM and modified form α-MEM culture medium containing 10% hyclone
4the cell suspension of individual/ml, is seeded in 96 well culture plates, and 200 μ l are inoculated in every hole, 37 DEG C, 5%CO
2cultivate.
(2) configure pharmaceutical sample mother solution (compound VS1 of the present invention), with 50%DMSO solution, the concussion of pharmaceutical sample incubation is dissolved, be configured to the solution that final concentration is 2mg/ml; And configuring the working solution of five times of dilutions, final concentration is 1mg/ml, 200 μ g/ml, 40 μ g/ml, 8 μ g/ml, 160ng/ml, 32ng/ml.
Configuration positive drug Nimustine (medicine that can be used for anti-nonsmall-cell lung cancer for known) 50mg/ml mother solution, and configure the working solution of five times of dilutions, final concentration is 1mg/ml, 200 μ g/ml, 40 μ g/ml, 8 μ g/ml, 160ng/ml, 32ng/ml.
Configuration solvent negative control mother solution 40%DMSO, working concentration is 40%, 8%, 1.6%, 0.32%, 0.064%, 0.0128%.
(3) culture medium containing variable concentrations sample renewed after 24h, then change the culture medium containing equal-volume solvent according to concentrations control group, often group establishes 3 parallel holes, 37 DEG C, 5%CO
2, cultivate 48h, observe under inverted microscope.
Abandoning supernatant after 48h, carefully cleans once with normal complete medium, and every hole adds the completely clear culture medium of 200 μ l, then adds 20 μ lCCK-8 reagent in every hole, and 37 DEG C are continued to cultivate 4h.After the mixing of miniature ultrasonic agitator, microplate reader is 450nm measures optical density value with tested wavelength.
According to the suppression ratio of medicine in variable concentrations cell growth, calculate IC
50value, as shown in table 1:
Table 1 medicine is at the IC of A549 and MRC-5
50value
As seen from the above table, the IC of VS1 and positive control medicine Nimustine
50be worth close, all have obvious inhibitory action to A549 Non-small cell lung carcinoma cell line; And for same medicine VS1, the IC of A549
50value is significantly less than the IC of MRC-5
50value, illustrates that the lethality of VS1 to A549 Non-small cell lung carcinoma cell is greater than the lethality to MRC-5 people's normal chick embryo lung fibroblast, has stronger selectivity, can be further used for the research and development of new Treatment for Non-small Cell Lung medicine.
Although above the present invention is described in detail with a general description of the specific embodiments, on basis of the present invention, can make some modifications or improvements it, this will be apparent to those skilled in the art.Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, all belong to the scope of protection of present invention.
Claims (7)
1. the application of compound VS1 in the anti-non-small cell lung cancer drug of preparation, is characterized in that: described compound VS1 chemical structural formula is as follows:
2. application according to claim 1, is characterized in that: described compound VS1 is as the one in sole active agent in described anti-non-small cell lung cancer drug or active ingredient group.
3. application according to claim 2, is characterized in that: other active component in described active ingredient group are chemical drugs or natural product.
4. the application according to any one of claim 1-3, is characterized in that: described anti-non-small cell lung cancer drug exists with the form of oral agents, cutaneous permeable agent or injection.
5. the application according to any one of claim 1-3, is characterized in that: described anti-non-small cell lung cancer drug is granule, tablet, capsule, injection.
6. the application according to any one of claim 1-3, is characterized in that: described anti-non-small cell lung cancer drug comprises pharmaceutically acceptable excipient further.
7. the application according to any one of claim 1-3, is characterized in that: described anti-nonsmall-cell lung cancer is adenocarcinoma of lung.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201510837217.2A CN105412089B (en) | 2015-11-26 | 2015-11-26 | Applications of the compound VS1 in anti-non-small cell lung cancer drug is prepared |
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| CN201510837217.2A CN105412089B (en) | 2015-11-26 | 2015-11-26 | Applications of the compound VS1 in anti-non-small cell lung cancer drug is prepared |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10072017B2 (en) | 2015-12-30 | 2018-09-11 | Flatley Discovery Lab, Llc | Compounds and methods for the treatment of cystic fibrosis |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP4029500A1 (en) * | 2021-01-15 | 2022-07-20 | Universidad Autónoma de Madrid | Tetrahydro-spiroindoline-pyrrolopyrrole-triones inhibitors of the nrf2-beta-trcp interaction for use in the treatment of nrf2-related diseases |
-
2015
- 2015-11-26 CN CN201510837217.2A patent/CN105412089B/en active Active
Non-Patent Citations (3)
| Title |
|---|
| 江萍等: "分子靶向联合治疗非小细胞肺癌研究进展", 《中国肿瘤临床与康复》 * |
| 赵雷磊等: "非小细胞肺癌靶向治疗药物的研究进展", 《中国药科大学学报》 * |
| 高蓓莉: "《支气管肺癌》", 30 April 2009, 中国医药科技出版社 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10072017B2 (en) | 2015-12-30 | 2018-09-11 | Flatley Discovery Lab, Llc | Compounds and methods for the treatment of cystic fibrosis |
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