CN107007586A - Iron death inhibitor is preparing the application in suppressing cardiotoxicity caused by doxorubicin medicine - Google Patents
Iron death inhibitor is preparing the application in suppressing cardiotoxicity caused by doxorubicin medicine Download PDFInfo
- Publication number
- CN107007586A CN107007586A CN201710137097.4A CN201710137097A CN107007586A CN 107007586 A CN107007586 A CN 107007586A CN 201710137097 A CN201710137097 A CN 201710137097A CN 107007586 A CN107007586 A CN 107007586A
- Authority
- CN
- China
- Prior art keywords
- iron
- adriamycin
- ferrostatin
- iron death
- caused
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
- A61K31/24—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
- A61K31/245—Amino benzoic acid types, e.g. procaine, novocaine
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of application of iron death inhibitor in the cardiotoxicity caused medicine for the treatment of anticancer drugs, doxorubicin is prepared, the iron death inhibitor is Ferrostatin 1.The present invention is proved through experiment in vivo, and Ferrostatin 1 is by suppressing the iron death process caused by adriamycin, so that lethal caused by doxorubicin cardiotoxicity is reduced, with significant protective effect.
Description
Technical field
The present invention relates to iron death inhibitor Ferrostatin-1 with antineoplastic adriamycin in use, energy
Significantly mitigate the cardiac toxic that adriamycin is caused.
Background technology
Adriamycin (Doxorubicin, DOX) belongs to anthracene nucleus antineoplastic antibiotic, wide with antitumor spectra, Synergistic action
By force, the features such as determined curative effect, it is widely used for treatment Malignancy and entity tumor, such as acute leukemia, lymph
Knurl, breast cancer, stomach cancer, soft tissue sarcoma and oophoroma etc..Similar with other antineoplastics, adriamycin is on the one hand to canceration
Cell has strong damaging action, on the other hand also has to normal cell and tissue and poisons, can cause alopecia, marrow
The toxicity such as suppression and cardiac toxic.Wherein, the maximum toxic side effect of adriamycin is irreversible cardiac toxic.Clinical manifestation
The lighter is arrhythmia cordis, and severe one is myocarditis or heart failure.This not only greatly affected the life quality of patient, also make Ah
The clinical practice of mycin is greatly limited.
Adriamycin is to cause cardiac damage by accumulation and dose-dependent mode to the toxicity of heart, but it causes cardiac muscle
The mechanism of damage is not fully apparent from yet.Research is thought and the excess generation, the peroxidization of lipid, DNA of active oxygen at present
Damage and the accumulation of tumor suppressor protein etc. are relevant.Increasing evidence shows in recent years, uses heart caused by adriamycin
Iron is crossed to be loaded in during its cardiac toxic develops and played an important role.Currently the only approval applied to clinical anti-Ah
Mycin cardiac toxic protective agent dexrazoxane (Dexrazoxane, DXZ) is exactly a kind of iron chelating agent.
The content of the invention
Treatment adriamycin is being prepared the technical problem to be solved in the present invention is to provide iron death inhibitor Ferrostatin-1
Application in cardiotoxic drugs, is that new drug development and innovative treatments provide basis.
In order to solve the above-mentioned technical problem, the present invention provides a kind of iron death inhibitor and is preparing treatment adriamycin Amplatzer duct occluder
Property medicine in application, the iron death inhibitor be Ferrostatin-1.
During invention, inventor has found that Fer-1 can significantly reduce heavy dose of (20 mgs/kg of the adriamycin of receiving
Body weight) injection mouse the death rate.Further mouse model is injected by middle dosage adriamycin (10 mg kg of body weight) to demonstrate,prove
Real, iron is dead caused by Ferrostatin-1 can substantially suppress iron overload, improves cardiac function, but does not change the group of mouse
Knit iron content.The result of study improves Adriamycin Cardiomyopathy for Ferrostatin-1 and provides theoretical foundation, particularly to correlation
Medicament research and development provides the foundation.
Iron death inhibitor Ferrostatin-1 is when treating doxorubicin cardiotoxicity, and its usage and consumption are：Abdomen every other day
Chamber injection ferrostatin-1 (1 mg kg of body weight), 7 days as one therapeutic course.
It can be used for the medicine for preparing treatment doxorubicin cardiotoxicity present invention finds iron death inhibitor Ferrostatin-1
Thing, expands the clinical practice of adriamycin.
For iron chelating agent, the research come in the past few decades thinks that iron has simply participated in Apoptosis wherein always
Or in the pathophysiological process of necrosis.With the development of cytobiology technology means, increasing novel cell is dead
Form is gradually found, wherein it is dead just to include iron.Iron death (Ferroptosis) is the cell death way that a class iron is relied on
Footpath, different from other apoptotic pathways such as apoptosis, necrosis, autophagy.Iron death shows as cytolipin levels of peroxide and mark base
Because of the rise of Ptgs2 expression quantity, specific it can be suppressed by iron chelator.Ferrostatin-1 (Fer-1) is generally acknowledged at present
Iron death inhibitor；As the compound containing N- cyclohexyl, Ferrostatin-1 has higher with cell membrane phospholipid bilayer
Compatibility, can effectively scavenger-cell membrane lipid peroxidatio, but it does not change the content of iron, cause so as to evade iron chelating agent
Many clinical side effects.So far the report that there is no iron death and its inhibitor to be acted in terms of doxorubicin cardiotoxicity.
That is, iron chelating agent suppresses iron death by lowering the iron content of tissue；And Fer-1 directly suppresses iron and causes iron dead
The lipid peroxidation process died, itself is (Fig. 4) for the content for not changing iron.Clinically, the use of iron chelating agent often by
Cause side effect in the content of excessive influence essential trace element iron.It can both suppress iron death using Fer-1, and not change
Iron content.
Adriamycin Cardiomyopathy is each extremely complex pathophysiological process, it is known that the death pathways participated just have
Apoptosis, necrosis, procedural necrosis, autophagy etc., the present invention identify a kind of new cell death way (iron is dead) and also assisted in
Wherein, its inhibitor can reduce toxicity of the adriamycin to heart.
In summary, the application the invention provides iron death inhibitor in treatment doxorubicin cardiotoxicity, the iron
Death inhibitor Ferrostatin-1 can be used for the medicine for preparing treatment anticancer drugs, doxorubicin cardiac side effects.Present invention warp
Experiment in vivo is proved, and Ferrostatin-1 is by suppressing the iron death process caused by adriamycin, so as to reduce adriamycin heart
Lethal caused by toxicity, with significant protective effect.The present invention is that the treatment of disease is overloaded with the dead iron for target spot of iron
Provided the foundation there is provided theoretical foundation, the particularly medicament research and development to Adriamycin Cardiomyopathy, with Clinical practicability.
Brief description of the drawings
The embodiment to the present invention is described in further detail below in conjunction with the accompanying drawings.
Fig. 1 is protective effect schematic diagrames of the survival rate aspect Fer-1 to mouse DOX cardiac toxics.
Fig. 2 is that Fer-1 reverses the dead schematic diagram of mouse heart iron caused by DOX, respectively with heart Ptgs2mRNA (A) and
Serum propane diols MDA (B) is index.
Fig. 3 is that Fer-1 reverses mouse heart failure schematic diagram caused by DOX, respectively with heart atrial natriuretic peptide (ANP)
MRNA (A), brain natriuretic peptide (BNP) mRNA (B) and myoglobulin heavy chain 7 (Myh7) mRNA (C) are index.
Fig. 4 is mouse heart non-heme iron content schematic diagram after Fer-1 is injected intraperitoneally 1 week.
Embodiment
With reference to specific embodiment, the present invention is described further, but protection scope of the present invention is not limited in
This.
1. material and method
1.1 experimental animal
6 SPF grades of week old C57BL/6 male mices are purchased from Shanghai Slac Experimental Animal Co., Ltd., and SPF environment is raised.
Standard feed AIN-76A (iron content 50mg/Kg, Research Diets, Inc) is adapted to after feeding 2 weeks, is divided at random by body weight
Group, every group 6~8.
1.2 medicines and processing
Compound monomer Fer-1 and adriamycin (DOX) are purchased from Selleck companies.Adriamycin is dissolved in physiological saline, Fer-
1 is dissolved in the physiological saline containing 2% (v/v) dimethyl sulfoxide (DMSO) DMSO, and Fer-1 concentration is 100 mcg/mls.Adriamycin point
Do not injected with 20 mg kg of body weight (lethal test) and 10 mg kg of body weight disposable celiacs；Fer-1 is with 1 milligram/public affairs
The dosage of the jin body weight next day, is injected intraperitoneally.After adriamycin is handled one week, 5% chloraldurate intraperitoneal anesthesia mouse, Culling heart blood, point
From serum, and collect heart tissue (Liquid nitrogen storage).
1.3RNA is extracted and the real-time PCR of fluorescent quantitation
Trizol (Life Technologies) method extracts the RNA of cell and tissue, and concrete operations by specification is carried out.
RNA purity (OD260/OD280 ≈ 1.9-2.1) and RNA concentration are detected on Nanodrop1000 Spectrophotometer
(ng/ μ l), adjustment RNA concentration to 1 μ g/ μ l.
After 2.0 μ g RNA are handled through DNase (Promega), M-MLV reverse transcriptase (Promega) and Oligo (dT)
18primer (Takara Bio Inc.) carries out reverse transcription.Fluorescence is carried out in CFX96Real-Time System (Bio-Rad)
Quantitative (Real-time PCR) in real time detection each related gene expression of mRNA level in-site, detection volume is 10ul, and reagent uses iQ
SYBR Green Supermix (Bio-Rad), primer sequence is as follows：
MouseGapdh:
Forward ATCATCCCTGCATCCACT
Reverse ATCCACGACGGACACATT
Mouse Ptgs2:
Forward CTGCGCCTTTTCAAGGATGG
Reverse GGGGATACACCTCTCCACCA
Mouse Anp:
Forward TCGTCTTGGCCTTTTGGCT
Reverse TCCAGGTGGTCTAGCAGGTTCT
Mouse Bnp:
Forward AAGTCCTAGCCAGTCTCCAGA
Reverse GAGCTGTCTCTGGGCCATTTC
Mouse Myh7:
Forward GCTGAAAGCAGAAAGAGATTATC
Reverse TGGAGTTCTTCTCTTCTGGAG。
The change of mRNA level in-site, as described in Fig. 2 (A) and Fig. 3 (A, B, C).
1.4 heart non-heme iron levels are determined
1 milliliter of tissue digestion liquid (3M hydrochloric acid 300ml/L, and 0.61M (10%) are added after heart tissue block is weighed
Ultra-pure water constant volume is to 1 liter after 99.735g/L trichloroacetic acids, dissolving), 65 DEG C of digestion are no less than 50 hours, middle shake oscillator
Vibrations three times, are no less than 10 minutes every time, it is ensured that tissue digestion completely, is settled to 1.5 milliliters with tissue digestion liquid afterwards.96
200 microlitres of iron nitrite ion working solution (iron nitrite ion liquid storages are added in orifice plate per hole：Saturated acetic acid sodium solution：Ultra-pure water=1:5:
5) 10 milliliters of samples, are added, are fully mixed, color development at room temperature 10 minutes.Absorbance (ELIASA) is read in 535nm wavelength, by group
Knit digestive juice and be set to blank, according to the absorbance computation organization non-heme iron content (Fig. 4) of iron titer.
1.5 Serum MDAs (MDA) are determined
Using thio barbital colorimetric method for determining MDA (MDA), operated in strict accordance with kit specification, kit purchase
Bioengineering Research Institute is built up from Nanjing.MDA is lipid peroxidation product, for indicating the dead generation of iron and degree (figure
2B)。
1.6 statistical method
Total data is represented using mean ± standard error (mean ± SEM), uses GraphPad Prism (version
6.0,GraphPad software；SanDiego, CA, USA) statistics software progress statistical analysis.P ＜ 0.05 represent difference
It is different to have conspicuousness, with statistical significance.
2. result
2.1 Ferrostatin-1 save dead mouse caused by adriamycin
2 groups are randomly divided into after the C57BL/6 male mices standard diet of 6 week old is balanced 2 weeks, while the milli of intraperitoneal injection 20
G/kg body weight adriamycin, one group is injected intraperitoneally Ferrostatin-1 (1 mg kg of body weight), another group of abdominal cavity note every other day
Isodose physiological saline is penetrated, whether daily timing observation mouse is dead.
As a result show, the survival rate of Ferrostatin-1 intervention groups is significantly higher than saline control group, point out
Level can suppress cellular damage and death caused by adriamycin to Ferrostatin-1 in vivo.
2.2 Ferrostatin-1 suppress heart failure and iron death caused by adriamycin
3 groups are randomly divided into after the C57BL/6 male mices standard diet of 6 week old is balanced 2 weeks, first group is control group, abdomen
Chamber injecting normal saline, two, three groups adriamycin (10 mg kg of body weight) is injected intraperitoneally.Adriamycin inject preceding 24 hours with
24 hours the 3rd group of intraperitoneal injection Ferrostatin-1 (1 mg kg of body weight) after injection.Adriamycin is solved after injecting 48 hours
Mouse is cutd open, damage to cardiac tissue label (atrial natriuretic peptide, brain natriuretic peptide and myoglobulin heavy chain 7mRNA levels) is detected,
Ptgs2mRNA levels, NADPH levels, Serum MDA (MDA) level, and heart non-heme iron content.
As a result show, adriamycin combination Ferrostatin-1 can substantially suppress the heart tissue significantly raised by adriamycin
Damage markers, point out its protective effect to cardiac toxic.
Meanwhile, second group is single adriamycin injection group heart tissue Ptgs2 mRNA level in-sites, NADPH levels and serum the third two
Aldehyde (MDA) level is significantly raised, and illustrates that adriamycin can inducing lipids peroxidating and iron be dead in vivo.It is combined Ferrostatin-
1 can substantially suppress these indexs, illustrate that level can suppress iron death caused by adriamycin to Ferrostatin-1 in vivo.
Finally, adriamycin and Ferrostatin-1 Combined Treatments group (the 3rd group) are with the independent treatment group (second of adriamycin
Group) to compare, heart non-heme iron content does not have notable difference, while illustrating that Ferrostatin-1 suppresses iron death, not
Influence the iron metabolism level of body.
Based on above-mentioned experiment, Ferrostatin-1, which suppresses iron overload, causes iron death to be treatment doxorubicin cardiotoxicity
Treatment method.
Finally, in addition it is also necessary to it is noted that listed above is only several specific embodiments of the invention.Obviously, this hair
It is bright to be not limited to above example, there can also be many deformations.One of ordinary skill in the art can be from present disclosure
All deformations for directly exporting or associating, are considered as protection scope of the present invention.
<110>Zhejiang University
<120>Iron death inhibitor is preparing the application in suppressing cardiotoxicity caused by doxorubicin medicine
<160> 10
<210> 1
<211> 18
<212> DNA
<213>Artificial sequence
<220>
<223>MouseGapdh primers Fs orward
<400> 1
atcatccctg catccact 18
<210> 2
<211> 18
<212> DNA
<213>Artificial sequence
<220>
<223>MouseGapdh primers Reverse
<400> 2
atccacgacg gacacatt 18
<210> 3
<211> 20
<212> DNA
<213>Artificial sequence
<220>
<223>Mouse Ptgs2 primers Fs orward
<400> 3
ctgcgccttt tcaaggatgg 20
<210> 4
<211> 20
<212> DNA
<213>Artificial sequence
<220>
<223>Mouse Ptgs2 primers Reverse
<400> 4
ggggatacac ctctccacca 20
<210> 5
<211> 19
<212> DNA
<213>Artificial sequence
<220>
<223>Mouse Anp primers Fs orward
<400> 5
tcgtcttggc cttttggct 19
<210> 6
<211> 22
<212> DNA
<213>Artificial sequence
<220>
<223>Mouse Anp primers Reverse
<400> 6
tccaggtggt ctagcaggtt ct 22
<210> 7
<211> 21
<212> DNA
<213>Artificial sequence
<220>
<223>Mouse Bnp primers Fs orward
<400> 7
aagtcctagc cagtctccag a 21
<210> 8
<211> 21
<212> DNA
<213>Artificial sequence
<220>
<223>Mouse Bnp primers Reverse
<400> 8
gagctgtctc tgggccattt c 21
<210> 9
<211> 23
<212> DNA
<213>Artificial sequence
<220>
<223>Mouse Myh7 primers Fs orward
<400> 9
gctgaaagca gaaagagatt atc 23
<210> 10
<211> 21
<212> DNA
<213>Artificial sequence
<220>
<223>Mouse Myh7 primers Reverse
<400> 10
tggagttctt ctcttctgga g 21
Claims (1)
1. application of the iron death inhibitor in the cardiotoxicity caused medicine for the treatment of anticancer drugs, doxorubicin is prepared, the iron is dead
Inhibitor is Ferrostatin-1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710137097.4A CN107007586B (en) | 2017-03-09 | 2017-03-09 | Application of iron death inhibitor in preparation of drug for inhibiting cardiotoxicity caused by adriamycin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710137097.4A CN107007586B (en) | 2017-03-09 | 2017-03-09 | Application of iron death inhibitor in preparation of drug for inhibiting cardiotoxicity caused by adriamycin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107007586A true CN107007586A (en) | 2017-08-04 |
| CN107007586B CN107007586B (en) | 2020-03-27 |
Family
ID=59440158
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710137097.4A Active CN107007586B (en) | 2017-03-09 | 2017-03-09 | Application of iron death inhibitor in preparation of drug for inhibiting cardiotoxicity caused by adriamycin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107007586B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111228513A (en) * | 2020-01-20 | 2020-06-05 | 重庆大学 | Amorphous calcium carbonate composite nano-drug with effect of inducing tumor cell iron death and preparation method thereof |
| CN111494605A (en) * | 2020-04-13 | 2020-08-07 | 中国人民解放军北部战区总医院 | Medical application of CREG protein in preventing or treating adriamycin myocardial damage |
| CN115006384A (en) * | 2022-07-20 | 2022-09-06 | 哈尔滨医科大学 | Application of iron death inhibitor in preparation of medicine for inhibiting cardiotoxicity caused by sorafenib |
-
2017
- 2017-03-09 CN CN201710137097.4A patent/CN107007586B/en active Active
Non-Patent Citations (2)
| Title |
|---|
| 曾杰 等.: "铁死亡相关机制、调控手段及相关疾病研究进展", 《中国药学杂志》 * |
| 车菲菲 等.: "右丙亚胺对阿霉素引起的心脏毒性防治效果及其机制研究.", 《四川大学学报（医学版）》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111228513A (en) * | 2020-01-20 | 2020-06-05 | 重庆大学 | Amorphous calcium carbonate composite nano-drug with effect of inducing tumor cell iron death and preparation method thereof |
| CN111228513B (en) * | 2020-01-20 | 2022-09-09 | 重庆大学 | Amorphous calcium carbonate composite nano-drug with effect of inducing tumor cell iron death and preparation method thereof |
| CN111494605A (en) * | 2020-04-13 | 2020-08-07 | 中国人民解放军北部战区总医院 | Medical application of CREG protein in preventing or treating adriamycin myocardial damage |
| CN111494605B (en) * | 2020-04-13 | 2023-07-25 | 中国人民解放军北部战区总医院 | Medical application of CREG protein in preventing or treating doxorubicin myocardial injury |
| CN115006384A (en) * | 2022-07-20 | 2022-09-06 | 哈尔滨医科大学 | Application of iron death inhibitor in preparation of medicine for inhibiting cardiotoxicity caused by sorafenib |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107007586B (en) | 2020-03-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| He et al. | Epigallocatechin-3-gallate pretreatment alleviates doxorubicin-induced ferroptosis and cardiotoxicity by upregulating AMPKα2 and activating adaptive autophagy | |
| He et al. | Ferroptosis and ferritinophagy in diabetes complications | |
| Sun et al. | Melatonin alleviates doxorubicin-induced mitochondrial oxidative damage and ferroptosis in cardiomyocytes by regulating YAP expression | |
| Yang et al. | Growth inhibition and induction of apoptosis in MCF-7 breast cancer cells by Antrodia camphorata | |
| Asensio-López et al. | Metformin protects against doxorubicin-induced cardiotoxicity: involvement of the adiponectin cardiac system | |
| US8822526B2 (en) | Synergistic pharmaceutical combination for the treatment of cancer | |
| US20070105790A1 (en) | Pancreatic cancer treatment using Na+/K+ ATPase inhibitors | |
| Sekar et al. | Antidiabetic effect of mangiferin in combination with oral hypoglycemic agents metformin and gliclazide | |
| CN107007586A (en) | Iron death inhibitor is preparing the application in suppressing cardiotoxicity caused by doxorubicin medicine | |
| Sato et al. | Sequence-dependent interaction between cisplatin and histone deacetylase inhibitors in human oral squamous cell carcinoma cells | |
| Chu et al. | Crocin protects against cardiotoxicity induced by doxorubicin through TLR-2/NF-κB signal pathway in vivo and vitro | |
| RU2644635C2 (en) | Systems, methods and compositions for cancer treatment | |
| Peng et al. | Puerarin activates adaptive autophagy and protects the myocardium against doxorubicin-induced cardiotoxicity via the 14–3-3γ/PKCε pathway | |
| Pirzeh et al. | Pretreatment with vildagliptin boosts ischemic-postconditioning effects on cardioprotection and expression profile of genes regulating autophagy and mitochondrial fission/fusion in diabetic heart with reperfusion injury | |
| CN107184586A (en) | Heme oxygenases-1 inhibitor is preparing the application in suppressing doxorubicin cardiotoxicity medicine | |
| Sangweni et al. | The triterpene, methyl-3β-hydroxylanosta-9, 24-dien-21-oate (RA3), attenuates high glucose-induced oxidative damage and apoptosis by improving energy metabolism | |
| CN111658655A (en) | Application of cucurbitacin B in preparation of iron death inducer and anti-nasopharyngeal carcinoma drug | |
| WO2019085827A1 (en) | New uses of desmethylclozapine | |
| US20230226060A1 (en) | Use of co-enzyme antagonists to slow metabolism | |
| CN110935028B (en) | Combined medicine for resisting heart failure and application thereof | |
| Lijuan et al. | Effect of artesunate on human endometrial carcinoma HEC-1B cells | |
| CN110840877A (en) | Application of dextro-lichenin alone or in combination with taxol in preparing medicine for treating and resisting lung squamous carcinoma | |
| US11110075B2 (en) | Use of daphnetin in improving function of aortic endothelial cell | |
| Weber | Critical issues in chemotherapy with tiazofurin | |
| KR101543983B1 (en) | Pharmaceutical composition containing novel histone deacetylase inhibitor for the prevention or treatment of cancer |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |