51 results about "Telomerase Inhibitor" patented technology

The present invention has identified compounds with extended aromatic chromophores that bind the G-quadruplex formed by the folding of single-stranded human telomeric DNA. These compounds have been shown to be effective telomerase inhibitors and are contemplated to be useful in developing cancer treatments. A model of cationic porphyrin interaction with quadruplex DNA by intercalation has been established and in combination with structure activity relations has provided novel porphyrin compounds that exhibit discrimination between binding duplex and quadruplex DNA and show improved activity against telomerase.

The invention provides methods and compositions for inhibiting telomerase activity and treatment of telomerase mediated conditions or diseases. The methods, compounds, and compositions of the invention may be employed alone, or in combination with other pharmacologically active agents, surgery, or radiation in the treatment of conditions or diseases mediated by telomerase activity, such as in the treatment of cancer.

A method and kit for inhibiting the proliferation of cancer cells are disclosed, based on a combination of a proteasome inhibitor and a telomerase inhibitor. When used in cancer therapy, the two compounds in combination enhance the anti-cancer treatment efficacy obtained with the proteasome inhibitor alone or the telomerase inhibitor alone. Preferably, efficacy is supraadditive or synergistic in nature relative to the combined effects of the individual agents, with minimal exacerbation of side effects.

One object of the present invention is to provide methods and compositions for inhibiting human telomerase, by providing inhibitors that bind to the CR4-CR5 or pseudoknot / template domains of the RNA component of human telomerase.

The invention provides a symmetrical difunctional coupling agent compound (I), i.e. N-fluorenylmethyloxycarbonyl-L-beta-glutamate-di-N-succinimide (Fmoc-beta-Glu(OSu)-OSu), and a production method thereof. Based on the compound, a series of novel coupling compounds which respectively contain a symmetrical difunctional coupling base, i.e. beta-Glu (beta-glutamate) are prepared through being coupled to ligand molecules; the structural formula of the series of coupling compounds is shown as (II), wherein M1 is a -NH2-contained ligand of a target molecule T1, M2 is a -NH2-contained ligand of a target molecule T2, L is a linking group, and S is a report signal group. The compound (1) provided by the invention has been used in coupling a targeted integrin alphavbeta3 receptor ligands, gastrin-releasing peptide receptor ligands, telomerase inhibitor pharmacophores and epidermal growth factor receptor ligands, and thus, a plurality of coupled bi-ligand molecular imaging agents and coupled tri-ligand molecular imaging agents are synthesized. The invention further relates to the use of the compound (I) and the series of novel coupling compounds (II) in the preparation of imaging agent drugs.

The invention provides methods and compositions for modulating the activity of therapeutic agents for the treatment of a cancer by administering one or more agents that (either alone or in combination) induces telomere damage and inhibits telomerase activity in the cancer cell. The method initially uses, e.g., a telomere damage-inducing agent such as paclitaxel, and a telomerase inhibitory agent such as AZT. The invention also provides methods for identifying other agents with telomere damage-inducing activity and / or telomerase inhibitory activity (as well as and compositions having such activity), for use in the treatment of cancer.

The present invention has identified thiaprophyrin, selenaporphyrin, and carotenoid porphyrin compounds that bind the G-quadruplex formed by the folding of single-stranded human telomeric DNA. These compounds have been shown to be effective telomerase and c-myc inhibitors and are contemplated to be useful in developing cancer treatments.

The invention discloses a method for screening a telomerase inhibitor with a quartz crystal microbalance. The method comprises the following steps: I, performing carboxyl-functionalizing of a chip surface; II, activating the chip surface; III, fixing a telomerase primer on the chip surface; IV, putting a chip on which the primer is fixed into a reactor of the quartz crystal microbalance, introducing a working solution into the reactor, reading the monitored frequency F1, then introducing a control solution, reading the monitored frequency F2, and calculating a difference (delta)F between F1 and F2; and V, putting the chip on which the primer is fixed into the reactor of the quartz crystal microbalance, introducing a working solution into the reactor, reading the monitored frequency F1', then introducing a liquid under test, reading the monitored frequency F2', calculating a difference (delta)F' between F1' and F2', and if F1' / (delta)F'<=50%, determining that the liquid under test contains the telomerase inhibitor. In the method disclosed by the invention, the quartz crystal microbalance is adopted as a detection tool, and the method has the advantages of no mark, real-time detection and the like.

Methods of reliably quantifying telomere length in cells or tissues that have been formalin fixed and paraffin embedded (FFPE) samples by quantitative polymerase chain reaction protocol and kits for use with such various methods are provided. The methods of the present invention may be used to predetermine an individual's response to treatment with a telomerase inhibitor, a telomere damaging agent or a telomerase activator.

A method, aerosol composition, and aerosolizing device for treating a brain tumor in a subject are disclosed. The method includes intranasally administering to the subject, an amount of a telomerase inhibitor, such as an oligonucleotide telomerase inhibitor, effective to inhibit growth of the tumor in the subject.

A method, aerosol composition, and aerosolizing device for treating a brain tumor in a subject are disclosed. The method includes intranasally administering to the subject, an amount of a telomerase inhibitor, such as an oligonucleotide telomerase inhibitor, effective to inhibit growth of the tumor in the subject.

The invention relates to the technical field of biology, in particular to a mesenchymal stem cell culture solution. The mesenchymal stem cell culture solution is prepared from the following components: human platelet lysate, mycillin (Pen Strep), long-acting glutamine, a chemotactic factor XCL1, a chemotactic factor CCL3, a heat shock protein (HSP70), a telomerase inhibitor IFN-alpha 2b and a basal culture medium DMEM. The components of the stem cell culture solution are wide in source, cultured mesenchymal stem cells are high in purity, quick in proliferation and good in dryness, and the mesenchymal stem cell culture solution is suitable for extracorporeal large-scale culture to conduct preclinical study and related clinical study.

The invention discloses a stem-loop structured combined probe and application thereof. The probe is constituted by two DNA sequences of stem-loop structures; from 5' terminals to 3' terminals, probe I and probe II sequentially include stem-loop zones and detection object recognition zones, and are applicable to telomerase activity, RNA and DNA detection and telomerase inhibitor screening; when a detection object is telomerase, the detection object recognition zone of the probe I is a telomerase substrate sequence, and the detection object recognition zone of the probe II is a sequence which is complementary with 8-40 bases in a telomerase extension sequence; and when the detection object is RNA or DNA, the detection object recognition zone of the probe I is a sequence which is complementary with 8-40 bases, close to the 3' terminal, of to-be-detected RAN or DNA, and the detection object recognition zone of the probe II is a sequence which is equal to 8-40 bases, close to the 5' terminal, of the to-be-detected RAN or DNA. The combined probe disclosed by the invention is unnecessary to make use of fluorescence labeling and radioactive element labeling, and the combined probe, with the specific stem-loop structure, provides a specific amplification template for a nucleic acid amplification reaction, so that rapid signal amplification under constant temperature is achieved; and the combined probe is high in sensitivity and amplification efficiency.

The invention discloses a trinuclear platinum complex (ZD028) capable of inhibiting the telomerase activity with high efficiency, a preparation method and an application of the trinuclear platinum as an antitumor drug. The trinuclear platinum complex can specifically inhibit the telomerase activity of the cancer cell, destroy a telomere maintenance mechanism which is pivotal to the cancer cell, accelerate the shortening of the telomere of the cancer cell, induce the aging of the cancer cell, and lead to death of the cancer cell to reach a purpose for treating malignant tumor, and the toxicity on normal cell is low. The conventional antitumor drug comprises doxorubicin, cisplatin and paclitaxel but not the limitation. Compared with the conventional antitumor drugs, the trinuclear platinum complex (ZD028) reduces the toxic and side effect on other organs or systems due to low toxicity on normal cells. The preparation method has the advantages of simple and easy operation and low cost, can be competed in a common chemical laboratory, and has no environmental pollution during the production process, thereby the trinuclear platinum complex (ZD028) can be used as a novel latent antitumor drug.

Provided herein are methods for reducing neoplastic progenitor cell proliferation and alleviating symptoms associated in individuals diagnosed with or thought to have Essential Thrombocythemia (ET). Also provided herein are methods for using telomerase inhibitors for maintaining blood platelet counts at relatively normal ranges in the blood of individuals diagnosed with or suspected of having ET.

Provided herein are methods for identifying individuals diagnosed with a cell proliferative disorder that will benefit from treatment with a telomerase inhibitor compound. Also provided herein are methods for treating these individuals with telomerase inhibitor compounds.

The present invention relates to methods of treating an inflammatory disease and / or cancer in a patient in need thereof, the method comprising administering a telomerase inhibitor to the patient.

The present invention relates to a combination treatment for hematological cancers. More specifically; a combination of a telomerase inhibitor and a Bcl-2 inhibitor are useful in treating hematological cancers, including AML. In certain embodiments, the telomerase inhibitor is imetelstat or imetelstat sodium and the Bcl-2 inhibitor is ABT-199.

The invention provides methods for determining the susceptibility of cancer patients to developing adverse reactions if treated with a telomerase inhibitor drug by measurement of telomere length in appropriate cells of the patient prior to initiation of the telomerase inhibitor treatment.

This document provides methods and materials involved in treating hematological malignancies. For example, methods and materials for using telomerase inhibitors to treat hematological malignancies such as hematological malignancies with a spliceosome mutation genotype or presenting with ringed sideroblasts within bone marrow are provided.

Provided herein are methods for reducing neoplastic progenitor cell proliferation and alleviating symptoms associated in individuals diagnosed with or thought to have myeloproliferative disorders, such as Essential Thrombocythemia (ET). Also provided herein are methods for using telomerase inhibitors for maintaining blood platelet counts at relatively normal ranges in the blood of individuals diagnosed with or suspected of having myeloproliferative disorders, such as ET.

The invention provides methods for determining the susceptibility of cancer patients to developing adverse reactions if treated with a telomerase inhibitor drug by measurement of telomere length in appropriate cells of the patient prior to initiation of the telomerase inhibitor treatment.

Provided herein are methods for identifying individuals diagnosed with a cell proliferative disorder that will benefit from treatment with a telomerase inhibitor compound. Also provided herein are methods for treating these individuals with telomerase inhibitor compounds.

The invention provides a telomerase inhibitor screening system based on an SPR technology. The system comprises a kit and an SPR chip, wherein the kit is provided with a first reaction liquid, a second reaction liquid and a diluent, the first reaction liquid comprises 100-120 mmol / L dNTP and a dNTP stock solution, and the second reaction liquid comprises telomerase and a telomerase stock solution; the diluent is 10-200 mmol / L PB or a PBS buffer solution which has pH of 7.3; the SPR chip is provided with a glass plate, a metal coating film covering the glass plate and telomeric DNA connected with the coating film. The telomerase inhibitor screening system based on the SPR technology can achieve simple, fast, stable and reliable screening work of telomerase inhibitors through mature SPR equipment on the market.

The invention provides application of a chiral metal supramolecular compound in preparing anti-tumor stem cell medicines, and belongs to the field of chiral metal supramolecular compounds. The chiral metal supramolecular compound is P enantiomer with [Ni2L3]<4+>; the P enantiomer is of a hexa-coordinate dextro-dinuclear metal triple-helical cylinder structure which is formed by two Ni<2+> and three ligands through coordinating bonds, and the structure formula of each ligand is shown in formula I. The Ni-P using as anti-tumor stem cell medicine has the advantages that the chiral selectivity is realized, the selectivity on telomere G-four-chain DNA (deoxyribonucleic acid) is strong, the growth of tumor stem cells and tumor cells is inhibited, the time for killing tumor stem cells is shorter than the killing time of other telomere enzyme inhibitors, the toxicity to normal somatic cells is small, and the like.

Provided herein are methods for identifying individuals diagnosed with a cell proliferative disorder that will benefit from treatment with a telomerase inhibitor compound. Also provided herein are methods for treating these individuals with telomerase inhibitor compounds. The methods comprise identifying individuals who will benefit from said treatment based on the average relative length of telomeres in cancer cells from said individuals.

The present invention provides a new application of triethylene tetramine as auxiliary medicine for resisting tumor. It uses the triethylene tetramine as telomerase inhibitor and can be matched with other conventional antitumor medicines including doxorubicin, carboplatin and taxol, etc. for curing and preventing tumor diseases.