15 results about "Maitansine" patented technology

The invention relates to novel cell-binding agent-maytansinoid conjugate having a self-immolative peptide linker and more specifically to conjugates of formula (I). The invention also provides novel maytansinoid compounds of formula (II), (III), (IV) or (V). The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention.

The invention relates to novel cell-binding agent-maytansinoid conjugate having a self-immolative peptide linker and more specifically to conjugates of formula (I). The invention also provides novel maytansinoid compounds of formula (II), (III), (IV) or (V). The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention.

To provide a method for treating patients having HER2-positive metastatic or locally advanced breast cancer in first-line therapy.SOLUTION: A method comprising administering a therapeutically effective amount of an anti-HER2 maytansinoid conjugate to a patient having breast cancer who has received prior treatment with a taxane.SELECTED DRAWING: None

The application discloses a nucleic acid aptamer of maytansine and application thereof, the nucleic acid aptamer is Seq2-X, and a DNA sequence of Seq2-X is shown as SEQ ID NO. 1. The nucleic acid aptamer can be combined with the target maytansine with high affinity and high specificity, the equilibrium dissociation constant is in the nanomolar range, the water solubility is good, and after being combined with the fat-soluble maytansine, the solubility of the drug can be improved. By utilizing the specific interaction between the nucleic acid aptamer and maytansine, the stability of maytansine drug can be improved, the cytotoxicity of maytansine is enhanced, and the treatment window is widened. By utilizing the nucleic acid aptamer as a drug delivery carrier of maytansine, the limitation of maytansine in clinical application can be improved, which has important significance for the design and development of maytansine drugs in clinical application.

The present invention concerns antibody-conjugate having general structure (2):wherein AB is an antibody capable of targeting Trop-2-expressing tumours and D is selected from the group consisting of taxanes, anthracyclines, camptothecins, epothilones, mytomycins, combretastatins, vinca alkaloids, maytansinoids, enediynes such as calicheamicins, duocarmycins, tubulysins, amatoxins, bleomycins, dolastatins and auristatins, pyrrolobenzodiazepine dimers, indolinobenzodiazepine dimers, radioisotopes, therapeutic proteins and peptides (or fragments thereof), kinase inhibitors, MEK inhibitors, KSP inhibitors, and analogues or prodrugs thereof. These antibody-conjugates exhibit an improved therapeutic index. The invention further concerns a process for preparing the antibody-conjugate according to the invention, a method for targeting Trop-2-expressing cells, medical uses of the antibody-conjugates according to the invention.

The present invention relates to drug combinations for the treatment of disease. In particular, the present invention relates to combinations comprising ligand-drug- conjugates targeting CD37 together with a co-agent selected from BCL2 inhibitors and inhibitors of the PI3K pathway and uses thereof in the treatment of cancer and especially DLBCL.

The present invention relates to peptide conjugates of microtubule targeting agents, such as maytansine derivatives, which are useful in treating diseases such as cancer.

Radiosensitizer prodrugs and formulations and methods of use thereof are provided. Typically, the radiosensitizer prodrug is an analog of a radiosensitizer parent compound having one or more S-nitrosothiol moieties. Typically, the S—N bond of the S-nitrosothiol moiety can be cleaved by radiation during radiotherapy, releasing the parent compound and nitric oxide. One or preferably both the parent compound and the nitric oxide can contribute to death of tumor cells exposed to radiotherapy. Nanoparticle formulations for delivery of the prodrug, and methods of using them in combination with radiotherapy to treat tumors and cancer are also provided.

The present application relates to conjugates of maytansinoids comprising a sortilin- targeting peptide and a linker, and salts thereof. These conjugates were shown to exhibit more potent antitumor effects than corresponding unconjugated maytansinoids in mouse models of Sortilin-expressing colorectal and breast cancers. The present application also relates to pharmaceutical compositions comprising the conjugates or salts thereof, as well as to methods and uses of the conjugates, salts thereof or pharmaceutical compositions for the treatment of Sortilin-expressing cancers.

The invention discloses a method for determining affinity by a micro-fluidic chip, the micro-fluidic chip and a nucleic acid aptamer, and the method comprises the following steps: reacting a quenching chain solution with gradient concentration with a nucleic acid aptamer solution, and determining a dissociation constant when the two chains are hybridized and balanced; the method comprises the following steps: reacting a maytansine solution with gradient concentration with a nucleic acid aptamer-quenching chain compound solution, and measuring a dissociation constant when maytansine and a nucleic acid aptamer-quenching chain compound are subjected to hybridization equilibrium; and calculating the balance constant of the combination of the aptamer and the maytansine. The micro-fluidic chip comprises a chip body, a digital micro-fluidic driving platform and a fluorescence detection module. The affinity is determined through the micro-fluidic chip, the affinity determination efficiency of the nucleic acid aptamer is remarkably improved, and the method has the advantages of low consumption, time saving and automation. The nucleic acid aptamer screened by the affinity screening method has high specificity and high affinity combination with maytansine, and is easy to synthesize, low in cost and stable in property.

The present invention relates to pharmaceutical combinations for the treatment of diseases. In particular, the present invention relates to combinations comprising a ligand-drug conjugate targeting CD37 and a adjuvant selected from the group consisting of a BCL2 inhibitor and a PI3K pathway inhibitor, and their use in the treatment of cancer, especially DLBCL.

The invention relates to 3-O-(N-alkyl)-carbamyl maytansine derivatives as well as a synthesis method and application thereof, and belongs to the technical field of natural medicinal chemistry and medical application. The invention firstly provides N-methyltransferase Asc-Orf2 capable of specifically catalyzing alkylation of 3-O-carbamoyl and a mutant of the N-methyltransferase Asc-Orf2, and the sequence of the N-methyltransferase Asc-Orf2 is shown as SEQ ID NO.1-6. And secondly, providing a 3-O-(N-alkyl)-carbamyl maytansine derivative with high anti-tumor activity, wherein the 3-O-(N-alkyl)-carbamyl maytansine derivative is prepared through a catalytic reaction of N-methyltransferase Asc-Orf2 or a mutant thereof. Finally, the invention provides a preparation method and application of the maytansine derivative. According to the invention, the N-methyltransferase Asc-Orf2 for specifically catalyzing the modification of the 3-O-carbamoyl is screened out, and the N-methyltransferase Asc-Orf2 can be used for preparing maytansine derivatives with the 3-O-(N-alkyl)-carbamoyl. The invention also provides a novel maytansine derivative with high anti-tumor activity, and compared with NDM without substituent group modification on 3-O-carbamoyl, the anti-tumor activity of the maytansine derivative is improved by 40-400 times.

Radiosensitizer prodrugs and formulations and methods of use thereof are provided. Typically, the radiosensitizer prodrug is an analog of a radiosensitizer parent compound having one or more S-nitrosothiol moieties. Typically, the S—N bond of the S-nitrosothiol moiety can be cleaved by radiation during radiotherapy, releasing the parent compound and nitric oxide. One or preferably both the parent compound and the nitric oxide can contribute to death of tumor cells exposed to radiotherapy. Nanoparticle formulations for delivery of the prodrug, and methods of using them in combination with radiotherapy to treat tumors and cancer are also provided.

The present invention concerns antibody-conjugates which are especially suitable for the targeting of PTK7-expressing cells, in particular tumour cells. The antibody-conjugates according to the invention have structure (1):Herein, AB is an antibody capable of targeting PTK7-expressing tumours; L is a linker that links Z to D; Z is a connecting group; L6 is -GlcNAc(Fuc)w-(G)j-S-(L7)w′-, wherein G is a monosaccharide, j is an integer in the range of 0-10, S is a sugar or a sugar derivative, GlcNAc is N-acetylglucosamine and Fuc is fucose, w is 0 or 1, w′ is 0, 1 or 2 and L7 is —N(H)C(O)CH2—, —N(H)C(O)CF2— or —CH2—; D is selected from the group consisting of anthracyclines, camptothecins, tubulysins, enediynes, amanitins, duocarmycins, maytansinoids, auristatins, eribulins, BCL-XL inhibitors, hemiasterlins, KSP inhibitors, TLR agonists, indolinobenzodiazepine dimers or pyrrolobenzodiazepine dimers (PBDs), and analogues or prodrugs thereof; b is 0 or 1; x is 1 or 2; and y is 1, 2, 3 or 4. The invention further concerns a method for preparing the antibody-conjugates of structure (1) and application of the antibody-conjugates of structure (1).

Provided herein are maytansinoid derivatives, conjugates thereof, and methods of treating or preventing proliferative diseases with the same.