CN103655573A - Application of pyrazolopyrimidine compound in preparation of transcription inhibitor medicine - Google Patents
Application of pyrazolopyrimidine compound in preparation of transcription inhibitor medicine Download PDFInfo
- Publication number
- CN103655573A CN103655573A CN201310533771.2A CN201310533771A CN103655573A CN 103655573 A CN103655573 A CN 103655573A CN 201310533771 A CN201310533771 A CN 201310533771A CN 103655573 A CN103655573 A CN 103655573A
- Authority
- CN
- China
- Prior art keywords
- medicine
- cell
- treatment
- tumor
- compound
- 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.)
- Pending
Links
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an application of 6-[4-[2-(1-piperidyl)ethoxy]phenyl]-3-(4-pyridyl)pyrazolo[1,5-A]pyrimidine in preparation of a transcription inhibitor medicine. The invention also discloses a pharmaceutical composition which is a preparation prepared by taking 6-[4-[2-(1-piperidyl)ethoxy]phenyl]-3-(4-pyridyl)pyrazolo[1,5-A]pyrimidine as an active ingredient accompanied by pharmaceutically acceptable accessories or auxiliary components. The 6-[4-[2-(1-piperidyl)ethoxy]phenyl]-3-(4-pyridyl)pyrazolo[1,5-A]pyrimidine disclosed by the invention can effectively inhibit cell transcription and induce tumor cell apoptosis, realizes an exact curative effect on lung cancer, liver cancer or cervical cancer, and has a good prospect in clinical application.
Description
Technical field
The present invention relates to 6-[4-[2-(piperidino) ethyoxyl] phenyl] purposes of-3-(4-pyridine radicals) pyrazolo [1,5-A] pyrimidine in preparing transcription inhibitor.
Background technology
Compound C, also be called dorsomorphin, 6-[4-[2-(piperidino) ethyoxyl] phenyl]-3-(4-pyridine radicals) pyrazolo [1,5-A] pyrimidine is from being formed with the separated a kind of natural small-molecule substance obtaining related substance with Brachydanio rerio dorsoventral axis.Compound C is 5 '-adenosine phosphate activated protein kinase (AMP-activated protein kinase; AMPK) and bone morphogenetic protein(BMP) (Bone morphogenetic protein; BMP) effective inhibitor (Zhou G of signal path; Myers R; Li Y, et al.Role of AMP-activated protein kinase in mechanism of metformin action.J.Clin.Invest.2001; 108 (8): 1167-1174; Yu PB, Hong CC, Sachidanandan C, et al.Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism.Nat.Chem.Biol.2008; 4 (1): 33-41.), can regulate the energy metabolism of body.
Recently there is report to point out also (Yang WL relevant to the autophagy of tumor cell of Compound C, Perillo W, Liou D, et al.AMPK inhibitor compound C suppresses cell proliferation by induction of apoptosis and autophagy in human colorectal cancer cells.J.Surg.Oncol.2012:Epub ahead of print; Peyton KJ; Yu Y; Yates B, et al.Compound C inhibits vascular smooth muscle cell proliferation and migration in an AMP-activated protein kinase-independent fashion.J.Pharmacol.Exp.Ther.2011; 338 (2): 476-484.).Autophagy (autophagy), to be proposed 1962 have the phenomenon of " oneself eats oneself " in discovery cell after by Ashford and Porter, refer to from compositions such as the duplicature wrapping portion kytoplasm coming off without ribosome attachment region of rough endoplasmic reticulum and the organelle of cell domestic demand degraded, protein and form autophagosome (autophagosome), and merge and form autophagy lysosome with lysosome, its content wrapping up of degrading, to realize, the metabolism of cell itself needs and the renewal of some organelle.Autophagy can be seen in the physiology of body and pathological process, and its role is positive or negative not yet illustrating, especially true to the research of tumor.
Transcribing is the significant process of cellular gene expression, and transcribing imbalance is one of major reason of tumor cell abnormality proliferation.Recently a large amount of reports are pointed out, transcribing of inhibition tumor cell can inducing tumor cell generation apoptosis (Chen R, Keating MJ, Gandhi V, et al.Transcription inhibition by flavopiridol:mechanism of chronic lymphocytic leukemia cell death.Blood 2005,106 (7): 2513-2519; Radhakrishnan SK, Gartel AL.A novel transcriptional inhibitor induces apoptosis in tumor cells and exhibits antiangiogenic activity.Cancer Res2006,66 (6): 3264-3270.).Clinical research also shows, transcription inhibitor can be used as Drug therapy tumor (Lin TS, Ruppert AS, Johnson AJ, Fischer B, Heerema NA, Andritsos LA, et al.Phase II study of flavopiridol in relapsed chronic lymphocytic leukemia demonstrating high response rates in genetically high-risk disease.J Clin Oncol2009,27 (35): 6012-6018.).
Pulmonary carcinoma is that M & M growth is the fastest, and population health and life are threatened to one of maximum malignant tumor.In all pulmonary carcinoma, more than 80% be nonsmall-cell lung cancer, and lung squamous cancer and adenocarcinoma of lung are two large topmost histological type in nonsmall-cell lung cancer.Over nearly 50 years, many countries all report that the M & M of pulmonary carcinoma all obviously increases, and male lung cancer M & M all accounts for first of all malignant tumor, and women's sickness rate accounts for second, and mortality rate accounts for second.The cause of disease of pulmonary carcinoma is still not exclusively clear and definite so far, and great mass of data shows, long-term a large amount of smoking and pulmonary carcinoma have a very close relationship.The treatment of pulmonary carcinoma adopts radiation and chemotherapy conventionally.
Hepatocarcinoma refers to the malignant tumor that betides liver, comprises two kinds of primary hepatocarcinoma and secondary liver cancers, and mostly the hepatocarcinoma of the daily theory of people is primary hepatocarcinoma if referring to.Primary hepatocarcinoma is one of modal malignant tumor clinically, and according to recent statistics, the annual new liver cancer patient approximately 600,000 in the whole world, occupies the 5th of malignant tumor.Primary hepatocarcinoma can be divided into Hepatocellular carcinoma, intrahepatic cholangiocarcinoma and mixed carcinoma of liver by cell typing.Diagnosis belongs to high morbidity in China, and general male is more than women.China is hepatitis B big country, and how the hepatocarcinoma of China develops on the basis of hbv-liver cirrhosis, and hepatitis C patient also, increasing gradually, also can develop into hepatocarcinoma after hepatitis B.China's number of the infected accounts for the more than half of the whole world at present, accounts for 55% of global hepatocarcinoma patient, has become a large killer of serious threat China people health and lives, and its danger can not look down upon.The treatment of hepatocarcinoma adopts radiation and chemotherapy conventionally.
Cervical cancer is one of women's common cancer, and it is to be caused by human papillomavirus (Human Papillomavirus is called for short HPV), and HPV virus can directly be propagated by contact skin, has the incubation period of more than ten years, therefore the initial stage is without any symptom.In the world, annual nearly 500,000 women in the whole world suffer from cervix uteri malignant tumor, die from 250,000 people that surpass of cervix uteri malignant tumor.In developing country, cervical cancer belongs to common multiple gynecological tumor, the seniority among brothers and sisters umber one.After the symptom of cervical cancer occurs three months, clients existing 2/3 is cancer of late stage, so cervix uteri tumor becomes the No.1 killer who threatens schoolgirl's life.Although cervix uteri tumor is unique cancer of finding out the reason of curing the disease up to now, but still consistent with general oncotherapy scheme at present for its treatment, all adopt chemotherapy radiotherapy, conventional chemicotherapy does not possess the specificity for tumor substantially, chemicotherapy also produces lethal effect to normal cell tumoricidal simultaneously, thereby human body is produced to very large toxic and side effects, also can cause the destruction of host immune system simultaneously, after chemicotherapy, easily cause that multiple complications and tumor easily recur, it is not very desirable that the feature of conventional chemicotherapy causes the curative effect of oncotherapy and prognosis.
Summary of the invention
The object of this invention is to provide 6-[4-[2-(piperidino) ethyoxyl] phenyl] the new purposes of-3-(4-pyridine radicals) pyrazolo [1,5-A] pyrimidine.
The invention provides 6-[4-[2-(piperidino) ethyoxyl] phenyl] purposes of-3-(4-pyridine radicals) pyrazolo [1,5-A] pyrimidine in preparing transcription inhibitor medicine.
Wherein, described transcription inhibitor medicine is antitumor drug.
Wherein, described antitumor drug is the medicine for the treatment of pulmonary carcinoma, hepatocarcinoma or cervical cancer.Preferably, the medicine of described treatment pulmonary carcinoma is the medicine for the treatment of nonsmall-cell lung cancer.Further preferably, the medicine of described treatment nonsmall-cell lung cancer is the medicine for the treatment of adenocarcinoma of lung.
The present invention also provides a kind of pharmaceutical composition with transcripting suppressioning action, it is with 6-[4-[2-(piperidino) ethyoxyl] phenyl]-3-(4-pyridine radicals) pyrazolo [1,5-A] pyrimidine is active component, adds the preparation that pharmaceutically acceptable adjuvant or complementary composition are prepared from.
The present invention also provides the purposes of aforementioned pharmaceutical composition in preparing antitumor drug.
Wherein, described antitumor drug is the medicine for the treatment of pulmonary carcinoma, hepatocarcinoma or cervical cancer.Preferably, the medicine of described treatment pulmonary carcinoma is the medicine for the treatment of nonsmall-cell lung cancer.Further preferably, the medicine of described treatment nonsmall-cell lung cancer is the medicine for the treatment of adenocarcinoma of lung.
6-[4-[2-of the present invention (piperidino) ethyoxyl] phenyl]-3-(4-pyridine radicals) pyrazolo [1,5-A] pyrimidine is a kind of good cell transcription inhibitor, can inducing apoptosis of tumour cell, can treat tumor disease, to the determined curative effect of pulmonary carcinoma, hepatocarcinoma or cervical cancer, potential applicability in clinical practice is good.
Obviously, according to foregoing of the present invention, according to ordinary skill knowledge and the customary means of this area, not departing under the above-mentioned basic fundamental thought of the present invention prerequisite, can also make modification, replacement or the change of other various ways.
The specific embodiment of form, is described in further detail foregoing of the present invention again by the following examples.But this should be interpreted as to the scope of the above-mentioned theme of the present invention only limits to following example.All technology realizing based on foregoing of the present invention all belong to scope of the present invention.
Figure of description
Fig. 1 Compound C suppresses to transcribe.Use respectively 0,5,10 μ m/L dosage Compound C to process lung cell A549, hepatoma carcinoma cell SMMC-7721 and cervical cancer cell HeLa, the processing time is 24 hours, detects cell transcription level.Transcription inhibitor DRB is as positive control, wherein, and * P<0.05vs.control.
Fig. 2 Compound C inducing apoptosis of tumour cell.A: use respectively 0,2.5,5,10 μ m/L dosage Compound C to process lung cell A549, hepatoma carcinoma cell SMMC-7721 and cervical cancer cell HeLa, the processing time is 24 hours, detects apoptotic proteins.B: process lung cell A549, hepatoma carcinoma cell SMMC-7721 and cervical cancer cell HeLa with 10 μ m/L dosage Compound C, the processing time is 0,12,24,36 hours, detects apoptotic proteins.C: use respectively 0,2.5,5,10 μ m/L dosage Compound C process lung cell A549, hepatoma carcinoma cell SMMC-7721 and cervical cancer cell HeLa, processing time is 24 hours, adopt Annexin V-FITC test kit and Apoptosis by Flow Cytometry, wherein, * P<0.05vs.0 μ M.D: process lung cell A549, hepatoma carcinoma cell SMMC-7721 and cervical cancer cell HeLa with 10 μ m/L dosage Compound C, processing time is 0,12,24,36 hours, adopt Annexin V-FITC test kit and Apoptosis by Flow Cytometry, wherein, * P<0.05vs.0h.
In Fig. 3 Compound C inhibition tumor cell Mice Body, become tumor.With lotus tumor in lung cell A549 and hepatoma carcinoma cell SMMC-7721 nude mouse, matched group normal saline intratumor injection, experimental group Compound C(15mg/kg, twice weekly) intratumor injection, observation analysis tumor size, wherein, * P<0.05vs. normal saline.
The specific embodiment
Experiment material:
1, cell strain
| Strain name | Title |
| A549 | Human lung adenocarcinoma cell line |
| SMMC-7721 | Human hepatoma cell strain |
| HeLa | Human cervical carcinoma cell lines |
2, tested medicine
Compound C:(6-[4-[2-(piperidino) ethyoxyl] phenyl]-3-(4-pyridine radicals) pyrazolo [1,5-A] pyrimidine), commercially available;
Positive drug: DRB5,6-dichloro-1-β-D-ribofuranosylbenzimidazole), commercially available.
3, main agents
AMPK inhibitor compound C, eIF2 α inhibitors of phosphatases salubrinal, autophagy inhibitor bafilomycin A1, transcription inhibitor 5,6-dichloro-1-β-D-ribobenzimidazole (DRB) and actinomycin D (ActD), p53 inhibitor PFT-α, caspase inhibitor z-VAD-fmk, Bcl-2 and Bcl-xl AB combined inhibitor T-263; Er stress derivant thapsigargin (Tg) and tunicamycin (Tun); GFP siRNA, p53siRNA, AMPK α siRNA; The Caspase-3 that Caspase-3(after eIF2 α, β-actin, phosphor-eIF2 α (Ser-51), phospho-p53 (Ser-15), AMPK α, p53, Bcl-2, Bcl-xl, PARP (poly ADP-ribose polymerase), shearing activates), LC3A/B primary antibodie; EIF2 α S51A plasmid.
Embodiment 1 Compound C suppresses the experiment of transcribing
1, experimental technique
(1) get commercially available tumor cell A549, SMMC-7721 and HeLa, cultivate;
Concrete cultural method is: with 10% hyclone DMEM culture medium culturing cell, be placed in CO
2(5%CO in incubator
2, 95% air, 37 ℃), optionally change liquid;
(2) adopt respectively 0,5,10 μ M/L dosage Compound C process above-mentioned cell, in culture medium, add 3H-uridine (3H-uridine) simultaneously, processing time is 24 hours, with transcription inhibitor DRB(5,6-dichloro-1-β-D-ribofuranosylbenzimidazole) as positive control;
(3) adopt 3H-uridine amount in liquid scintillation instrument analysis of cells, analyze transcriptional level.
2, experimental result
When cell is transcribed, need to use uridine, therefore, the in the situation that of adding 3H-uridine in culture medium, cell transcription level is higher, and in cell, the content of 3H-uridine is higher.
Experimental result as shown in Figure 1, compare with negative control, after Compound C of the present invention processes, 3H uridine (3H-uridine) content of tumor cell A549, SMMC-7721 and HeLa significantly decline (p<0.05), when Compound C using dosage is 10 μ m/L, the amount of 3H uridine is suitable with positive drug DRB.
Experimental result explanation, the bright Compound C of the present invention is transcribing of inhibition tumor cell A549, SMMC-7721 and HeLa effectively, is a kind of respond well transcription inhibitor, can be used for the medicine that tumor disease is treated in preparation.
Embodiment 2 Compound C promote the experiment of apoptosis of tumor cells
1, experimental technique
The impact of 1.1 variable concentrations Compound C on apoptotic proteins (Caspase-3 after PARP, shearing)
(1) get commercially available tumor cell A549, SMMC-7721 and HeLa, cultivate;
Concrete cultural method is: with 10% hyclone DMEM culture medium culturing cell, be placed in CO
2(5%CO in incubator
2, 95% air, 37 ℃), optionally change liquid;
(2) use respectively 0,2.5,5,10 μ m/L dosage Compound C to process above-mentioned cell, the processing time is 24 hours, receives cell;
(3) get cell, cracking, by the lysate obtaining BCA standard measure, then uses SDS degeneration;
(4), by above-mentioned protein sample SDS-PAGE, Western blot analyzes, and determines the impact of Compound C on 2 kinds of apoptotic proteins.
1.2Compound C processes the impact of different time on apoptotic proteins (Caspase-3 after PARP, shearing)
(1) get commercially available tumor cell A549, SMMC-7721 and HeLa, cultivate;
Concrete cultural method is: with 10% hyclone DMEM culture medium culturing cell, be placed in CO
2(5%CO in incubator
2, 95% air, 37 ℃), optionally change liquid;
(2) with 10 μ m/L dosage Compound C, stimulate above-mentioned cell, the processing time is 0,12,24,36 hours, receives cell;
(3) get cell, cracking, by the lysate obtaining BCA standard measure, then uses SDS degeneration;
(4) above-mentioned protein sample SDS-PAGE, Western blot analyzes the impact of Compound C on 2 kinds of apoptotic proteins.
1.3 impacts of variable concentrations Compound C on apoptosis of tumor cells
(1) get commercially available tumor cell A549, SMMC-7721 and HeLa, cultivate;
Concrete cultural method is: with 10% hyclone DMEM culture medium culturing cell, be placed in CO
2(5%CO in incubator
2, 95% air, 37 ℃), optionally change liquid;
(2) use respectively 0,2.5,5,10 μ m/L dosage Compound C to stimulate above-mentioned cell, the processing time is 24 hours, receives cell;
(3) adopt Annexin V-FITC test kit by the impact of flow cytometry analysis Compound C on apoptosis;
(4) statistical analysis data.
1.4Compound C processes the impact of different time on apoptosis of tumor cells
(1) get commercially available tumor cell A549, SMMC-7721 and HeLa, cultivate;
Concrete cultural method is: with 10% hyclone DMEM culture medium culturing cell, be placed in CO
2(5%CO in incubator
2, 95% air, 37 ℃), optionally change liquid;
(2) with 10 μ m/L dosage Compound C, stimulate above-mentioned cell, the processing time is 0,12,24,36 hours, receives cell;
(3) adopt Annexin V-FITC test kit by the impact of flow cytometry analysis Compound C on apoptosis;
(4) statistical analysis data.
2, experimental result
Experimental result as shown in Figure 2, compare with matched group, after Compound C of the present invention processes, in tumor cell A549, SMMC-7721 and HeLa, the expression of the two kinds of apoptotic proteins of Caspase-3 after PARP and shearing obviously improves, and has concentration and time dependence (Fig. 2 a, Fig. 2 b); Compare with matched group, after Compound C of the present invention processes, in tumor cell A549, SMMC-7721 and HeLa, apoptosis rate significantly raises (p<0.05), and has concentration and time dependence (Fig. 2 c, Fig. 2 d).
Experimental result explanation, Compound C can promote apoptotic proteins high expressed, inducing apoptosis of tumour cell can be used for preparing the medicine of the tumor diseases such as Hepatoma therapy, pulmonary carcinoma and cervical cancer.
In embodiment 3 Compound C inhibition tumor cell bodies, become the experiment of tumor
1, laboratory animal
Source, germline: BALB/c-nu nude mice is purchased from The 2nd Army Medical College Experimental Animal Center.
Age, body weight: 6 week age, about 20g.
Sex: male.
Size of animal: 6 every group.
2, experimental technique
(1) get commercially available tumor cell A549 and SMMC-7721, cultivate;
Concrete cultural method is: with 10% hyclone DMEM culture medium culturing cell, be placed in CO
2(5%CO in incubator
2, 95% air, 37 ℃) cultivate;
(2) raise the nude mice of size in 6 week age;
(3) (cell injection volume is 1 * 10 in mouse bare subcutaneous injection inoculation to get A549 and SMMC-7721 cell
7/ only);
(4) administration after subcutaneous injection 7d, experimental group nude mice intratumor injection Compound C, injected dose is 15mg/kg, weekly twice, using normal saline as negative control group.Observe the growing state of tumor body in nude mouse and measure tumor volume, while inoculating latter the 24th day, tumor in A549 body being taken out and observed, inoculation, in the time of latter the 27th day, is observed tumor taking-up in SMMC-7721 body.
2, experimental result
Experimental result is as shown in Fig. 3 a～3b, and negative control group is along with inoculation time extends, tumor rapid growth in the body of tumor cell A549, SMMC-7721; Compare with negative control group, after Compound C of the present invention processes, in tumor cell A549, SMMC-7721 body, the growth rate of tumor significantly slows down, from inoculating the 6th day, the interior tumor volume of tumor cell A549 body is significantly less than negative control group (p<0.05), and (Fig. 3 a), from inoculating the 9th day, in tumor cell SMMC-7721 body, tumor volume is significantly less than negative control group (p<0.05) (Fig. 3 b).
Experimental result explanation, Compound C is the one-tenth tumor of inhibition tumor cell in nude mouse effectively, and treatment tumor disease is especially clear and definite to the curative effect of hepatocarcinoma and pulmonary carcinoma.
To sum up, 6-[4-[2-(piperidino) ethyoxyl] phenyl]-3-(4-pyridine radicals) pyrazolo [1,5-A] pyrimidine can effectively suppress cell transcription, inducing apoptosis of tumour cell, the determined curative effect to pulmonary carcinoma, hepatocarcinoma and cervical cancer.
Claims (10)
1.6-[4-[2-(piperidino) ethyoxyl] phenyl] purposes of-3-(4-pyridine radicals) pyrazolo [1,5-A] pyrimidine in preparing transcription inhibitor medicine.
2. purposes according to claim 1, is characterized in that: described transcription inhibitor medicine is antitumor drug.
3. purposes according to claim 2, is characterized in that: described antitumor drug is the medicine for the treatment of pulmonary carcinoma, hepatocarcinoma or cervical cancer.
4. purposes according to claim 3, is characterized in that: the medicine of described treatment pulmonary carcinoma is the medicine for the treatment of nonsmall-cell lung cancer.
5. purposes according to claim 4, is characterized in that: the medicine of described treatment nonsmall-cell lung cancer is the medicine for the treatment of adenocarcinoma of lung.
6. a pharmaceutical composition, it is characterized in that: it is with 6-[4-[2-(piperidino) ethyoxyl] phenyl]-3-(4-pyridine radicals) pyrazolo [1,5-A] pyrimidine is active component, adds the preparation that pharmaceutically acceptable adjuvant or complementary composition are prepared from.
7. the purposes of pharmaceutical composition claimed in claim 6 in preparing transcription inhibitor medicine.
8. purposes according to claim 7, is characterized in that: described transcription inhibitor medicine is antitumor drug.
9. purposes according to claim 8, is characterized in that: described antitumor drug is the medicine for the treatment of pulmonary carcinoma, hepatocarcinoma or cervical cancer.
10. purposes according to claim 9, is characterized in that: the medicine of described treatment pulmonary carcinoma is the medicine for the treatment of nonsmall-cell lung cancer;
Preferably, the medicine of described treatment nonsmall-cell lung cancer is the medicine for the treatment of adenocarcinoma of lung.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310533771.2A CN103655573A (en) | 2013-10-11 | 2013-10-31 | Application of pyrazolopyrimidine compound in preparation of transcription inhibitor medicine |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310473577.X | 2013-10-11 | ||
| CN201310473577 | 2013-10-11 | ||
| CN201310533771.2A CN103655573A (en) | 2013-10-11 | 2013-10-31 | Application of pyrazolopyrimidine compound in preparation of transcription inhibitor medicine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103655573A true CN103655573A (en) | 2014-03-26 |
Family
ID=50295135
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310533771.2A Pending CN103655573A (en) | 2013-10-11 | 2013-10-31 | Application of pyrazolopyrimidine compound in preparation of transcription inhibitor medicine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103655573A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020000704A1 (en) * | 2018-06-29 | 2020-01-02 | 中国科学院深圳先进技术研究院 | Use of ampk inhibitor, compound c, in drug for treating tumors |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013016452A2 (en) * | 2011-07-25 | 2013-01-31 | Vanderbilt University | Cancer treatment using bmp inhibitor |
-
2013
- 2013-10-31 CN CN201310533771.2A patent/CN103655573A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013016452A2 (en) * | 2011-07-25 | 2013-01-31 | Vanderbilt University | Cancer treatment using bmp inhibitor |
Non-Patent Citations (2)
| Title |
|---|
| JUNFEI JIN等: "AMPK inhibitor Compound C stimulates ceramide production and promotes Bax redistribution and apoptosis in MCF7 breast carcinoma cells", 《JOURNAL OF LIPID RESEARCH》 * |
| 陈吉生: "《新编临床药物学》", 31 August 2013, 中国中医药出版社 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020000704A1 (en) * | 2018-06-29 | 2020-01-02 | 中国科学院深圳先进技术研究院 | Use of ampk inhibitor, compound c, in drug for treating tumors |
| CN110652515A (en) * | 2018-06-29 | 2020-01-07 | 中国科学院深圳先进技术研究院 | Application of AMPK inhibitor Compound C in tumor treatment drug |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Jiang et al. | Oridonin‐induced mitochondria‐dependent apoptosis in esophageal cancer cells by inhibiting PI3K/AKT/mTOR and Ras/Raf pathways | |
| Liu et al. | Shikonin induces apoptosis and prosurvival autophagy in human melanoma A375 cells via ROS-mediated ER stress and p38 pathways | |
| Hsu et al. | The triterpenoids of Hibiscus syriacus induce apoptosis and inhibit cell migration in breast cancer cells | |
| Charette et al. | Salirasib inhibits the growth of hepatocarcinoma cell lines in vitro and tumor growth in vivo through ras and mTOR inhibition | |
| He et al. | Effects of notch signaling pathway in cervical cancer by curcumin mediated photodynamic therapy and its possible mechanisms in vitro and in vivo | |
| Yin et al. | RETRACTED ARTICLE: Ginsenoside-Rg1 enhances angiogenesis and ameliorates ventricular remodeling in a rat model of myocardial infarction | |
| Gamarra-Luques et al. | Mifepristone prevents repopulation of ovarian cancer cells escaping cisplatin-paclitaxel therapy | |
| Dung et al. | PP2A mediates diosmin p53 activation to block HA22T cell proliferation and tumor growth in xenografted nude mice through PI3K–Akt–MDM2 signaling suppression | |
| Park et al. | Dehydrocostuslactone inhibits LPS-induced inflammation by p38MAPK-dependent induction of hemeoxygenase-1 in vitro and improves survival of mice in CLP-induced sepsis in vivo | |
| Liu et al. | Neferine inhibits proliferation and collagen synthesis induced by high glucose in cardiac fibroblasts and reduces cardiac fibrosis in diabetic mice | |
| Zhou et al. | Metformin inhibits cell proliferation in SKM-1 cells via AMPK-mediated cell cycle arrest | |
| Han et al. | L-securinine induces apoptosis in the human promyelocytic leukemia cell line HL-60 and influences the expression of genes involved in the PI3K/AKT/mTOR signaling pathway | |
| Wang et al. | Oridonin induces G2/M cell cycle arrest and apoptosis in human oral squamous cell carcinoma | |
| Dai et al. | Inhibition of mTOR/eIF4E by anti-viral drug ribavirin effectively enhances the effects of paclitaxel in oral tongue squamous cell carcinoma | |
| Guo et al. | (-)-β-hydrastine suppresses the proliferation and invasion of human lung adenocarcinoma cells by inhibiting PAK4 kinase activity | |
| Liu et al. | Enhanced antitumor effect of shikonin by inhibiting Endoplasmic Reticulum Stress via JNK/c-Jun pathway in human glioblastoma stem cells | |
| Su et al. | Cordycepin, isolated from medicinal fungus Cordyceps sinensis, enhances radiosensitivity of oral cancer associated with modulation of DNA damage repair | |
| Jia et al. | Garcinol suppresses RANKL‐induced osteoclastogenesis and its underlying mechanism | |
| Wang et al. | Effects of a checkpoint kinase inhibitor, AZD7762, on tumor suppression and bone remodeling | |
| Du et al. | Japonicone A inhibits the growth of non-small cell lung cancer cells via mitochondria-mediated pathways | |
| Shen et al. | Pien Tze Huang inhibits the proliferation of human colon carcinoma cells by arresting G1/S cell cycle progression | |
| Cen et al. | Honokiol induces apoptosis of lung squamous cell carcinoma by targeting FGF2‐FGFR1 autocrine loop | |
| Kuo et al. | Lack of compensatory pAKT activation and eIF4E phosphorylation of lymphoma cells towards mTOR inhibitor, RAD001 | |
| Wang et al. | TIPE‑2 suppresses growth and aggressiveness of hepatocellular carcinoma cells through downregulation of the phosphoinositide 3‑kinase/AKT signaling pathway | |
| Yi et al. | Natural product corynoline suppresses melanoma cell growth through inducing oxidative stress |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20140326 |
|
| RJ01 | Rejection of invention patent application after publication |