CN110200959A - A kind of application of flavone compound - Google Patents
A kind of application of flavone compound Download PDFInfo
- Publication number
- CN110200959A CN110200959A CN201910460460.5A CN201910460460A CN110200959A CN 110200959 A CN110200959 A CN 110200959A CN 201910460460 A CN201910460460 A CN 201910460460A CN 110200959 A CN110200959 A CN 110200959A
- Authority
- CN
- China
- Prior art keywords
- compound
- cell
- protein
- albumen
- flavone 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
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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Abstract
The present invention relates to a kind of applications of flavone compound, the flavone compound 3,3', 4', 5,7- pentahydroxyflavone dihydrate proves that the compound can effectively inhibit PD-1/PD-L1 protein-interacting by ELISA and protein fluorescence quenching experiments, and has stronger affinity interaction to PD-L1 albumen.Number of cell clones is formed and ELISA detection IL-2 secretion is experiments have shown that the compound can effectively enhance T lymph Jurkat cell to the anti-tumor activity of MDA-MB-231 and NCI-H460 tumour cell and the expression of IL-2, and then reverse T cell immunosupress.Research achievement of the invention provides a kind of drug to target the immunotherapy of tumors of PD-1/PD-L1 immunity inspection point.
Description
Technical field
The present invention relates to a kind of application of small molecule compound, especially a kind of application of flavone compound.
Background technique
T cell is important immunocyte, plays critical function during anti-tumor immunotherapy.The work of T cell
Change is the process of a height adjustment, in addition to the first signal (TCR and the MHC- Antigenic Peptide knot for needing T cell receptor (TCR) to conduct
Close) outside, it is also necessary to cooperate with the second signal that signaling molecule (costimulatory signal and coinhibitory signals) provide altogether to promote or press down
T cell responses processed, wherein second signal is the key that cause T cell antigen specificity response.Signaling molecule receptor protein packet altogether
Include the molecules such as CD28, PD-1, CTLA-4, ICOS, BTLA, LAG3, TIM3 and OX40, wherein CD28, OX40 and ICOS be for
Submission costimulatory signal to activate t cell immune response, and PD-1, CTLA-4, BTLA, LAG3 and TIM3 receptor protein be for
Submission coinhibitory signals inhibit t cell immune response in turn.
PD-1 albumen is a kind of unique Inhibitory receptor, is expressed during initiating antigen mediating T-cell activation by TCR
In T cell surface, adjustment signal plays a significant role in tumor immune escape, inflammation, autoimmune disease etc..PD-1
(CD279) there are two ligands: PD-L1 (B7-H1) and PD-L2 (B7-DC), is able to suppress T lymph as PD-1 and ligand binding
The proliferation of cell and the secretion for reducing relevant cell factor are suppressed immune response such as IL-2 and γ-IFN, thus
Promote the immunologic escape of tumour cell.
The immunosupress letter that PD-1/PD-L1 immunity inspection point inhibitor can block PD-1/PD-L1 signal path to mediate
Number.The inhibitor for targeting PD-1/PD-L1 immunity inspection point at present is mainly anti-PD-1 and anti-PD-L1 monoclonal antibody,
The antibody class drug of listing has 6 kinds, be respectively the Keytruda of Mo Shadong, Bristol Myers Squibb Opdivo (Nivolumab),
The Tecentrip (Atezolizumab) of Roche, the Bacencio (Acelumab) of Pfizer and Merck KGaA, Britain and Switzerland Ah
The Imfinzi (Durvalumab) of Si Likang, the Libtayo (Cemiplimab-rwlc) that Sino is luxuriant and rich with fragrance and regeneration is first.However, this
A little drugs, which have, lacks oral availability, limited tissue and the factors limitation such as tumor infiltrating, expensive.Small molecule chemical combination
Object has high stability, easy penetrability, property easy to maintain, low cost and convenient oral characteristic, has wide development and application
Space.
Summary of the invention
Technical problem to be solved by the present invention lies in provide a kind of application of flavone compound.
The technical solution adopted by the present invention is that:
A kind of flavone compound with antioxidant activity obtained from plant, 3,3', 4', 5,7- pentahydroxyflavones
Dihydrate (alias: two water Quercetins or two water oaks essence), has structure shown in formula (I):
Above compound is bought from selleck company, purity 99.06%.
Above-mentioned flavone compound as PD-1/PD-L1 protein-interacting inhibitor in terms of application.
The flavone compound has stronger affinity interaction to PD-L1 albumen.
Application of the above-mentioned flavone compound in terms of preparing anti-tumor drug.
Preferably, the application of above-mentioned flavone compound, the anti-tumor drug are using PD-1/PD-L1 as the swollen of target spot
Tumor immunotherapy medicaments.
The flavone compound can obviously increase Jurkat cell to the tumour of MDA-MB-231 and NCI-H460 cell
Killing activity.
The flavone compound increases the expression of Jurkat cell IL-2.
The flavone compound is as inhibition PD-1/PD-L1 protein-interacting, PD-1/PD-L1 immunosupress letter
Number and reverse the immunosuppressive application of T cell.
The beneficial effects of the present invention are:
Above-mentioned flavone compound can effectively inhibit the interaction between PD-1/PD-L1 albumen.Protein fluorescence is quenched
Go out experiments have shown that the small molecule compound and PD-L1 albumen have a stronger affine activity, monoclonal formed co-culture experiments and
ELISA detects IL-2 secretion experiments have shown that the compound can enhance Jurkat cell to MDA-MB-231 and NCI-H460 cell
Anti-tumor activity, and raise the expression of Jurkat cell IL-2.These results indicate that the small molecule compound can inhibit
PD-1/PD-L1 protein-interacting and the transmitting of PD-1/PD-L1 signal, reverse T cell immunosupress, can be used as and target
The drug of the immunotherapy of tumors of PD-1/PD-L1 immunity inspection point.
Detailed description of the invention
Fig. 1 is that the present invention utilizes ELISA method to screen inhibition PD-1/PD-L1 protein-interacting from natural compound libraries
Small molecule compound as a result, compound I (number 12) is small molecule compound of the present invention.Fig. 1 a is small molecule
It closes and the His-Trx-PD-1 and GST-PD-L1 suppression result to interact is summarized when object concentration is 5 μM, Fig. 1 b is that have inhibition to live
Property the inhibitory effect that interacts to His-Trx-PD-1 and GST-PD-L1 of 14 kinds of small molecule compounds.
The inhibitory effect to interact when Fig. 2 is compound I various concentration to His-Trx-PD-1 and GST-PD-L1.
Fig. 3 is the PD-1-Fc-His and PD- that the present invention verifies that compound I expresses HEK293 cell using ELISA method
The inhibitory effect of L1-His-Biotin protein-interacting.Fig. 3 a is Compound I concentration when being 5 μM to PD-1-Fc-His and
The inhibitory effect of PD-L1-His-Biotin interaction, to PD-1-Fc-His and PD- when Fig. 3 b is compound I various concentration
The inhibitory effect of L1-His-Biotin interaction.
Fig. 4 is that the present invention utilizes protein fluorescence quenching method detection compound I to the affine of His-HA-PD-L1 albumen
Activity.Fig. 4 a is that influence is quenched on His-HA-PD-L1 protein fluorescence in buffer (DMSO content is 0.5%), and Fig. 4 b is chemical combination
Influence is quenched on His-HA-PD-L1 protein fluorescence in object I.
Fig. 5 is that the present invention utilizes affine work of the protein fluorescence quenching method detection compound I to His-HA-PD-1 albumen
Property.Fig. 5 a is that influence is quenched on His-HA-PD-1 protein fluorescence in buffer (DMSO content is 0.5%), and Fig. 5 b is compound I
Influence is quenched on His-HA-PD-1 protein fluorescence.
Fig. 6 is that the present invention forms experiment detection Jurkat cell using cell monoclonal and MDA-MB-231 cell co-cultures
Influence of the compound I to Jurkat cell killing activity in system.
Fig. 7 is that the present invention forms experiment detection Jurkat cell using cell monoclonal and NCI-H460 cell co-cultures body
Influence of the compound I to Jurkat cell killing activity in system.
Fig. 8 is that the present invention utilizes expression of the compound I to Jurkat cell IL-2 in ELISA method detection co-culture system
Situation.Fig. 8 a is that Jurkat cell and MDA-MB-231 cell co-culture IL-2 expression, and Fig. 8 b is Jurkat cell and NCI-
H460 cell co-cultures IL-2 expression.
Specific embodiment
Below with reference to embodiment, the present invention is further described, but embodiment does not limit the scope of the invention.
Embodiment 1
(1) inhibitor screening of PD-1/PD-L1 protein-interacting
1. with the His-Trx-PD-1 fusion protein of carbonate coating buffer dilution Bacillus coli expression to 1 μ g/mL,
The every hole 100 μ L is added in 96 hole elisa Plates, is placed in 4 DEG C overnight.It is washed 3 times with 1 × PBST, the closing of 5% skimmed milk power, every hole
300 μ L, 37 DEG C of closing 2hrs.
2. being washed 3 times with 1 × PBST.1 × PBS dilutes GST and GST-PD-L1 albumen to 2 μ g/mL, simultaneously respectively simultaneously
The DMSO or small molecule compound (5 μM of final concentration) of 0.2 μ L is added, mixes, the every hole 100 μ L is added in 96 orifice plates, 37 DEG C of combinations
2hrs.1 × PBST is washed 3 times, and the diluted GST antibody (rabbit polyclonal antibody) of 100 1 × PBS of μ L, 37 DEG C of combinations are added in every hole
2hrs.1 × PBST is washed 3 times, and the goat anti-rabbit antibodies of the diluted HRP label of 100 1 × PBS of μ L, 37 DEG C of combinations are added in every hole
0.5hrs。
3. being washed 5 times with 1 × PBST, 100 μ L tmb substrate developing solutions of every hole addition, normal-temperature reaction 5-10min, in equal volume
The 2M concentrated sulfuric acid terminate reaction, read under Tecan multi-function microplate reader 450nm wavelength.According to all numerical value references in GST-PD-
L1 (DMSO) group is calculated and is mapped.Fig. 1 is the results show that between compound I inhibition His-Trx-PD-1 and GST-PD-L1 albumen
Interaction.
4. compound I is carried out concentration doubling dilution (19.5nM, 39nM, 78nM, 156nM, 312.5nM, 625nM, 1.25
μM,2.5μM,5μM,10μM).According between method detection compound I inhibition His-Trx-PD-1 and GST-PD-L1 albumen in (1)
Interaction and draw compound I suppression curve.As a result as shown in Fig. 2, compound can effectively inhibit Bacillus coli expression
Interaction between PD-1/PD-L1 albumen.
(2) compound I inhibits the PD-1/PD-L1 protein-interacting of HEK293 cell expression
1. carbonate is coated with PD-L1-Fc-His protein 1 the μ g/mL, 100 μ L of buffer dilution HEK293 cell expression
Every hole is added in 96 hole elisa Plates, is placed in 4 DEG C overnight.It is washed 3 times with 1 × PBST, the closing of 5% skimmed milk power, every 300 μ L of hole,
37 DEG C of closing 2hrs.
2. being washed 3 times with 1 × PBST.1 × PBS dilutes PD-L1-His-biotin albumen to 1 μ g/mL simultaneously, adds simultaneously
Enter the DMSO or small molecule compound (5 μM of final concentration) of 0.2 μ L, mix, the every hole 100 μ L is added in 96 orifice plates, 37 DEG C of combinations
2hrs.1 × PBST is washed 3 times, and the Streptavidin of the diluted HRP label of 100 1 × PBS of μ L, 37 DEG C of combinations are added in every hole
0.5hrs.1 × PBST is washed 5 times, and 100 μ L tmb substrate developing solutions, normal-temperature reaction 5-10min, isometric 2M is added in every hole
The concentrated sulfuric acid terminates reaction, reads under Tecan multi-function microplate reader 450nm wavelength.Fig. 3 a is the results show that compound I inhibits HEK-
Interaction between the PD-1/PD-L1 albumen of 293 cells expression.
3. compound I is carried out concentration doubling dilution (19.5nM, 39nM, 78nM, 156nM, 312.5nM, 625nM, 1.25
μM,2.5μM,5μM,10μM).Inhibit PD-1-Fc-His and PD-L1-His-biotin according to method detection compound I in (2)
Interaction between albumen simultaneously draws compound I suppression curve.As a result as shown in Figure 3b, compound I effectively inhibits HEK293 thin
Interaction between the PD-1/PD-L1 albumen of cellular expression.
(3) detection compound I and the affine activity of PD-1 or PD-L1 is quenched in protein fluorescence
His-HA-PD-L1 or His-HA-PD-1 albumen is diluted with buffer (50mM Na-P, 150mMNaCl pH7.4)
To 0.05mg/mL, volume 2mL, solution is subjected to protein fluorescence spectroscopic assay.The excitation wavelength of fixed Fluorescence Spectrometer is
The slit width of 280nm, transmitting range 300-500nm, excitation and transmitting is set to 5nm and 2.5nm, at room temperature
Scan different samples.Fluorescence titration experiment is the concentration of fixing protein, ceaselessly changes the concentration of small molecule compound, is surveyed
Determine the variation of the fluorescence spectrum of protein.Concrete operations are as follows: compound concentration is that the compound I mother liquor of 0.25mM (takes 2 μ L to be dissolved in
The 50mM small molecule compound of DMSO is diluted with 400 μ L buffers), 10 μ L mother liquors are added dropwise every time in above-mentioned solution, mix,
The fluorescence spectrum variation for measuring protein, is added dropwise 10 times altogether.
As a result as shown in Figures 4 and 5, influence is quenched very on His-HA-PD-L1 and His-HA-PD-1 protein fluorescence in buffer
It is small, and compound is quenched His-HA-PD-L1 and His-HA-PD-1 protein fluorescence and has a significant effect, wherein His-HA-PD-L1
It is maximum that influence is quenched in protein fluorescence.The result shows that compound I and His-HA-PD-L1 albumen have stronger affine activity.
(4) monoclonal forms experiment detection Jurkat cell to the killing activity of tumour cell
10%FBS DMEM or 1640 culture mediums are resuspended MDA-MB-231 or NCI-H460 cell and count, with 1 × 104
A/hole is inoculated in 12 orifice plates, is placed in 37 DEG C of incubators and is cultivated rs for 24 hours.Activation is resuspended with 1640 culture medium of 10%FBS
Jurkat cell (2 μ g/ml PHA stimulate 48hrs) simultaneously counts, while extremely being closed with 1640 culture medium diluted compounds I of 10%FBS
Suitable concentration, exhausts culture supernatant in 12 orifice plates, is respectively Jurkat of the ratio by activation of 4:1 and 8:1 according to effect target ratio (E:T)
Cell and the compound I diluted are added jointly in 12 orifice plates, make final concentration of 0 μM, 10 μM, 20 μM and 40 μ of small-molecule drug
M continues to co-culture 48hrs, and control group is not inoculated with Jurkat cell.The Jurkat cell for removing and suspending is washed with 1 × PBS, it is residual
The tumour cell stayed is dyed with crystal violet dye liquor, observes monoclonal forming quantity in orifice plate.
As a result as shown in Figures 6 and 7, with the increase of Compound I concentration, orifice plate inner cell quantity is gradually decreased;Same
Under the conditions of drug concentration, with the increase of effect target ratio, orifice plate inner cell quantity is gradually decreased compared to no Jurkat cell group.With
Above the result shows that, compound I increases Jurkat cell to the killing activity of MDA-MB-31 and NCI-H460 cell.
(5) it is horizontal to detect Jurkat cell secretion IL-2 by ELISA
10%FBS DMEM or 1640 culture mediums are resuspended MDA-MB-231 or NCI-H460 cell and simultaneously count, with 5000/
Hole is inoculated in 96 orifice plates, is placed in 37 DEG C of incubators and is cultivated rs for 24 hours.Activation is resuspended with 1640 culture medium of 10%FBS
Jurkat cell (2 μ g/ml PHA stimulate 48hrs) simultaneously counts, while extremely being closed with 1640 culture medium diluted compounds I of 10%FBS
Suitable concentration, exhausts culture supernatant in 96 orifice plates, and the compound I diluted the Jurkat cell activated with 40000 is added jointly
Enter in 96 orifice plates, make final concentration of 0 μM, 10 μM, 20 μM and 40 μM of small-molecule drug, co-cultures rs for 24 hours.Supernatant is harvested, is utilized
Human IL-2's ELISA detection kit measures the expression of IL-2 in supernatant.
As a result as shown in figure 8, the compound of the present invention I can activate Jurkat cell to discharge IL-2, exempting from for T cell is reversed
Epidemic disease inhibits.
Above-described embodiment is illustrative rather than limits to a kind of detailed description that the application of flavone compound carries out
Qualitatively, several embodiments, therefore the variation in the case where not departing from present general inventive concept can be enumerated according to limited range
And modification, it should belong within protection scope of the present invention.
Claims (3)
1. a kind of flavone compound as PD-1/PD-L1 protein-interacting inhibitor in terms of application, the flavonoids
Compound is 3,3', 4', 5, and 7- pentahydroxyflavone dihydrate has structure shown in formula (I):
2. application of the flavone compound described in claim 1 in terms of preparing anti-tumor drug.
3. application according to claim 2, the anti-tumor drug is to control by the tumour immunity of target spot of PD-1/PD-L1
Treat drug.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910460460.5A CN110200959A (en) | 2019-05-30 | 2019-05-30 | A kind of application of flavone compound |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910460460.5A CN110200959A (en) | 2019-05-30 | 2019-05-30 | A kind of application of flavone compound |
Publications (1)
Publication Number | Publication Date |
---|---|
CN110200959A true CN110200959A (en) | 2019-09-06 |
Family
ID=67789468
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201910460460.5A Pending CN110200959A (en) | 2019-05-30 | 2019-05-30 | A kind of application of flavone compound |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN110200959A (en) |
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11059834B2 (en) | 2017-08-08 | 2021-07-13 | Chemocentryx, Inc. | Macrocyclic immunomodulators |
US11130740B2 (en) | 2017-04-25 | 2021-09-28 | Arbutus Biopharma Corporation | Substituted 2,3-dihydro-1H-indene analogs and methods using same |
US11135210B2 (en) | 2018-02-22 | 2021-10-05 | Chemocentryx, Inc. | Indane-amines as PD-L1 antagonists |
CN113509551A (en) * | 2021-08-11 | 2021-10-19 | 四川大学 | Quercetin iron ion micelle and application thereof in tumor photothermal immunotherapy |
US11266643B2 (en) | 2019-05-15 | 2022-03-08 | Chemocentryx, Inc. | Triaryl compounds for treatment of PD-L1 diseases |
US11426364B2 (en) | 2016-06-27 | 2022-08-30 | Chemocentryx, Inc. | Immunomodulator compounds |
US11485708B2 (en) | 2019-06-20 | 2022-11-01 | Chemocentryx, Inc. | Compounds for treatment of PD-L1 diseases |
US11708326B2 (en) | 2017-07-28 | 2023-07-25 | Chemocentryx, Inc. | Immunomodulator compounds |
US11713307B2 (en) | 2019-10-16 | 2023-08-01 | Chemocentryx, Inc. | Heteroaryl-biphenyl amides for the treatment of PD-L1 diseases |
US11866429B2 (en) | 2019-10-16 | 2024-01-09 | Chemocentryx, Inc. | Heteroaryl-biphenyl amines for the treatment of PD-L1 diseases |
US11872217B2 (en) | 2019-07-10 | 2024-01-16 | Chemocentryx, Inc. | Indanes as PD-L1 inhibitors |
-
2019
- 2019-05-30 CN CN201910460460.5A patent/CN110200959A/en active Pending
Non-Patent Citations (5)
Title |
---|
ARJUN PATRA等: "Formulation and evaluation of mixed polymeric micelles of quercetin for treatment of breast, ovarian, and multidrug resistant cancers", 《INTERNATIONAL JOURNAL OF NANOMEDICINE》 * |
AYSEGUL TURA等: "Expression of the programmed cell death ligand 1 (PD-L1) on uveal melanoma cells with Monosomy-3", 《INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE》 * |
LEI JING等: "Establishment of the Method for Screening Small Molecule Inhibitors Blocking the Interaction Between PD-1 and Its Ligand PD-L1", 《ADVANCES IN APPLIED BIOTECHNOLOGY》 * |
LILIANA MOREIRA等: "Quercetin and epigallocatechin gallate inhibit glucose uptake and metabolism by breast cancer cells by an estrogen receptor-independent mechanism", 《EXPERIMENTAL CELL RESEARCH》 * |
M. GONIOTAKI等: "Encapsulation of naturally occurring flavonoids into liposomes: physicochemical properties and biological activity against human cancer cell lines", 《JOURNAL OF PHARMACY AND PHARMACOLOGY》 * |
Cited By (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11793771B2 (en) | 2016-06-27 | 2023-10-24 | Chemocentryx, Inc. | Immunomodulator compounds |
US11426364B2 (en) | 2016-06-27 | 2022-08-30 | Chemocentryx, Inc. | Immunomodulator compounds |
US11130740B2 (en) | 2017-04-25 | 2021-09-28 | Arbutus Biopharma Corporation | Substituted 2,3-dihydro-1H-indene analogs and methods using same |
US11708326B2 (en) | 2017-07-28 | 2023-07-25 | Chemocentryx, Inc. | Immunomodulator compounds |
US11691985B2 (en) | 2017-08-08 | 2023-07-04 | Chemocentryx, Inc. | Macrocyclic immunomodulators |
US11059834B2 (en) | 2017-08-08 | 2021-07-13 | Chemocentryx, Inc. | Macrocyclic immunomodulators |
US11135210B2 (en) | 2018-02-22 | 2021-10-05 | Chemocentryx, Inc. | Indane-amines as PD-L1 antagonists |
US11759458B2 (en) | 2018-02-22 | 2023-09-19 | Chemocentryx, Inc. | Indane-amines as PD-L1 antagonists |
US11266643B2 (en) | 2019-05-15 | 2022-03-08 | Chemocentryx, Inc. | Triaryl compounds for treatment of PD-L1 diseases |
US11485708B2 (en) | 2019-06-20 | 2022-11-01 | Chemocentryx, Inc. | Compounds for treatment of PD-L1 diseases |
US11872217B2 (en) | 2019-07-10 | 2024-01-16 | Chemocentryx, Inc. | Indanes as PD-L1 inhibitors |
US11713307B2 (en) | 2019-10-16 | 2023-08-01 | Chemocentryx, Inc. | Heteroaryl-biphenyl amides for the treatment of PD-L1 diseases |
US11866429B2 (en) | 2019-10-16 | 2024-01-09 | Chemocentryx, Inc. | Heteroaryl-biphenyl amines for the treatment of PD-L1 diseases |
CN113509551A (en) * | 2021-08-11 | 2021-10-19 | 四川大学 | Quercetin iron ion micelle and application thereof in tumor photothermal immunotherapy |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN110200959A (en) | A kind of application of flavone compound | |
Sun et al. | Targeting glycosylated PD-1 induces potent antitumor immunity | |
Qian et al. | A monoclonal antibody-based sensitive enzyme-linked immunosorbent assay (ELISA) for the analysis of the organophosphorous pesticides chlorpyrifos-methyl in real samples | |
Schoenfeld et al. | BRCA2 is ubiquitinated in vivo and interacts with USP11, a deubiquitinating enzyme that exhibits prosurvival function in the cellular response to DNA damage | |
Brown et al. | High-throughput, multiplexed IgG subclassing of antigen-specific antibodies from clinical samples | |
Zhang et al. | Production of ultrasensitive generic monoclonal antibodies against major aflatoxins using a modified two-step screening procedure | |
Eisen et al. | A myeloma protein with antibody activity | |
KR102621034B1 (en) | GDF-15 as a diagnostic marker to predict the clinical course of treatment with immune checkpoint blockers | |
CN105717296B (en) | A kind of biological activity determination method of anti-PD-L1 monoclonal antibodies | |
RU2012118643A (en) | ANTIBODIES AGAINST SIGLEK-15 FOR TREATMENT OF DISEASE CONNECTED WITH BONE MASS LOSS | |
Tayade et al. | A novel zinc (ii) and hydrogen sulphate selective fluorescent “turn-on” chemosensor based on isonicotiamide: INHIBIT type's logic gate and application in cancer cell imaging | |
Zhang et al. | Ultrasensitive and selective detection of Staphylococcus aureus using a novel IgY-based colorimetric platform | |
D’Alessandro et al. | 1 H-NMR metabolomics reveals the Glabrescione B exacerbation of glycolytic metabolism beside the cell growth inhibitory effect in glioma | |
Abdiche et al. | Label-free epitope binning assays of monoclonal antibodies enable the identification of antigen heterogeneity | |
Ji et al. | Nanobodies based on a sandwich immunoassay for the detection of staphylococcal enterotoxin B free from interference by protein A | |
US20160245815A1 (en) | Method for detecting pancreatic tumor, antibodies, and kit for the detection of pancreatic tumor | |
CN112433055A (en) | Method for detecting biological activity of PVRIG antibody based on reporter gene method | |
Devlin et al. | Production of a broad specificity antibody for the development and validation of an optical SPR screening method for free and intracellular microcystins and nodularin in cyanobacteria cultures | |
Liang et al. | Development of a monoclonal antibody-based ELISA for the detection of Alternaria mycotoxin tenuazonic acid in food samples | |
CN114414808A (en) | Method for detecting synergistic biological activity of TIGIT antibody and PVRIG antibody | |
Ma et al. | Reversal of P-glycoprotein-mediated multidrug resistance by a synthetic α-aminoxy peptidomimetic | |
Thompson et al. | High-throughput quantitation of Fc-containing recombinant proteins in cell culture supernatant by fluorescence polarization spectroscopy | |
Puligedda et al. | Capture and display of antibodies secreted by hybridoma cells enables fluorescent on-cell screening | |
Sato et al. | Preparation of an antigen-responsive fluorogenic immunosensor by tyrosine chemical modification of the antibody complementarity determining region | |
Fu et al. | A reporter gene assay for determining the biological activity of therapeutic antibodies targeting TIGIT |
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 | ||
WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20190906 |
|
WD01 | Invention patent application deemed withdrawn after publication |