120205-52-9

Upstream product

• 1149-26-4 (S)-N-(benzyloxycarbonyl)valine 
• 120205-48-3 tert-Butyl (3R,4S,5S)-3-methoxy-4-(N-methylamino)-5-methylheptanoate hydrochloride 
• 474645-22-2 tert-Butyl (3R,4S,5S)-3-methoxy-4-(N-methylamino)-5-methylheptanoate 
• 878-23-9 2-bromo-1-ethylpyridin-1-ium tetrafluoroborate 
• 4083-57-2 2,4-dimethylpent-3-ylamine 
• 80029-43-2 1-hydroxybenzotriazol-hydrate 
• 72-18-4 L-valine 
• 1859-49-0 (2S,3S)-2-(benzylamino)-3-methylpentanoic acid 
• 73-32-5 L-isoleucine 
• 870640-64-5 tert-butyl (3R,4S,5S)-4-[benzyl(methyl)amino]-3-methoxy-5-methyl heptanoate 
• 154633-73-5 tert-Butyl (3S,4S,5S)-3-methoxy-4--5-methylheptanoate 
• 120205-56-3 benzyl methyl[(2S,3S)-3-methyl-1-oxopentan-2-yl]carbamate 
• 120205-55-2 benzyl [(2S,3S)-1-hydroxy-3-methylpentan-2-yl]methylcarbamate 
• 120205-57-4 tert-Butyl (3S,4S,5S)-3-hydroxy-4--5-methylheptanoate 

Downstream Products

• 120205-53-0 (3R,4S,5S)-tert-butyl 4-((S)-2-((S)-2-(dimethylamino)-3-methylbutanamido)-N,3-dimethylbutanamido)-3-methoxy-5-methylheptanoate 
• 1369426-89-0 benzyl N-{(2R,3R)-3-methoxy-2-methyl-3-[(2S)-pyrrolidin-2-yl]propanoyl}-L-phenylalaninate trifluoroacetate 
• 161485-88-7 methyl (S)-2-((2R,3R)-3-methoxy-2-methyl-3-((S)-pyrrolidin-2-yl)propanamido)-3-phenylpropanoate 2,2,2-trifluoroacetate 
• 1369426-94-7 benzyl N-{(2R,3R)-3-methoxy-2-methyl-3-[(2S)-pyrrolidin-2-yl]propanoyl}-L-tryptophanate trifluoroacetate 
• 1369427-25-7 benzyl (1S,2R)-1-amino-2-phenylcyclopropanecarboxylate 
• 1369427-12-2 adamantan-1-ylmethyl N-(tert-butoxycarbonyl)-L-phenylalaninate 
• 1369427-33-7 N^α-{(2R,3R)-3-methoxy-2-methyl-3-[(2S)-pyrrolidin-2-yl]propanoyl}-L-tryptophanamide trifluoroacetate 

Relevant academic research and scientific papers

Synthesis and evaluation of novel dolastatin 10 derivatives for versatile conjugations

Dolastatin 10 (1) is a highly potent cytotoxic microtubule inhibitor (cytotoxicity IC50 5.0 nM) and several of its analogs have recently been used as payloads in antibody drug conjugates. Herein, we describe the design and synthesis of a series of novel dolastatin 10 analogs useful as payloads for conjugated drugs. We explored analogs containing functional groups at the thiazole moiety at the C-terminal of dolastatin 10. The functional groups included amines, alcohols, and thiols, which are representative structures used in known conjugated drugs. These novel analogs showed excellent potency in a tumor cell proliferation assay, and thus this series of dolastatin 10 analogs is suitable as versatile payloads in conjugated drugs. Insights into the structure–activity relationships of the analogs are also discussed.

Rational Design of Azastatin as a Potential ADC Payload with Reduced Bystander Killing

Auristatins are a class of ultrapotent microtubule inhibitors, whose growing clinical popularity in oncology is based upon their use as payloads in antibody-drug conjugates (ADCs). The most widely utilized auristatin, MMAE, has however been shown to cause apoptosis in non-pathological cells proximal to the tumour (“bystander killing”). Herein, we introduce azastatins, a new class of auristatin derivatives encompassing a side chain amine for antibody conjugation. The synthesis of Cbz-azastatin methyl ester, which included the C2-elongation and diastereoselective reduction of two proteinogenic amino acids as key transformations, was accomplished in 22 steps and 0.76 % overall yield. While Cbz-protected azastatin methyl ester (0.13–3.0 nM) inhibited proliferation more potently than MMAE (0.47–6.5 nM), removal of the Cbz-group yielded dramatically increased IC50-values (9.8–170 nM). We attribute the reduced apparent cytotoxicity of the deprotected azastatin methyl esters to a lack of membrane permeability. These results clearly establish the azastatins as a novel class of cytotoxic payloads ideally suited for use in next-generation ADC development.

CONJUGATE OF MONOMETHYL AURISTATIN F AND TRASTUZUMAB AND ITS USE FOR THE TREATMENT OF CANCER

The present invention relates to an antibody-drug-conjugate or pharmaceutical composition comprising the same. From one aspect, the invention relates to an antibody-drug-conjugate (ADC) comprising an antibody consisting of the Trastuzumab or a biosimilar thereof, said antibody being conjugated to at least one drug consisting of a monomethyl auristatin F derivative. The invention also comprises method of treatment of cancer comprising administering to the subject an effective amount of said antibody-drug-conjugate or composition comprising the same.

COMPOSITION FOR THE TREATMENT OF IGF-1R EXPRESSING CANCER

The present invention relates to a method for the treatment of IGF-IR expressing cancers as well as to a compositions and a kit for said traitment. From one aspect, the invention reates to the combined use of a first antibody for the determination of the IGF-IR status of a cancer and a second antibody used as an ADC for the treatment of said cancer.

REACTION MEDIUM CONTAINING WATER-SURFACTANT MIXTURE

The present invention is directed to reaction mixtures comprising a water-surfactant mixture and a co-solvent. This technology reduced the amount of organic solvents needed for performing chemical reactions. Furthermore, compared to reaction mixtures lack

CONJUGATE OF MONOMETHYL AURISTATIN F AND TRASTUZUMAB AND ITS USE FOR THE TREATMENT OF CANCER

The present invention relates to an antibody-drug-conjugate. From one aspect, the invention relates to an antibody-drug-conjugate comprising an antibody consisting of the Trastuzumab, said antibody being conjugated to at least one drug consisting of a monomethyl auristatin F derivative. The invention also comprises method of treatment and the use of said antibody-drug-conjugate for the treatment of cancer.

CYTOTOXIC AND ANTI-MITOTIC COMPOUNDS, AND METHODS OF USING THE SAME

Compounds having cytotoxic and/or anti-mitotic activity are disclosed. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed. Also disclosed are compositions having the structure: (T)-(L)-(D), wherein (T) is a targeting moiety, (L) is an optional linker, and (D) is a compound having cytotoxic and/or anti-mitotic activity.

ANTIBODY-DRUG-CONJUGATE AND ITS USE FOR THE TREATMENT OF CANCER

The present invention relates to an antibody-drug-conjugate. From one aspect, the invention relates to an antibody-drug-conjugate comprising an antibody capable of binding to a Target, said antibody being conjugated to at least one drug selected from derivatives of dolastatin 10 and auristatins. The invention also comprises method of treatment and the use of said antibody-drug-conjugate for the treatment of cancer.

NEW ANTIBODY DRUG CONJUGATES (ADCS) AND THE USE THEREOF

The present application relates to new antibody drug conjugates (ADCs) of N,N dialkylauristatins directed against the target FGFR2, drug metabolites of said ADCs, a method for producing said ADCs, the use of said ADCs for the treatment and/or prevention of illnesses as well as the use of said ADCs for producing pharmaceuticals for the treatment and/or prevention of illnesses, particularly of hyperproliferative and/or angiogenic diseases such as carcinosis. Such treatments can be carried out as monotherapy or in combination with other pharmaceuticals or additional therapeutic measures.

NOVEL BINDER-DRUG CONJUGATES (ADCs) AND USE OF SAME

The present patent application relates to novel binder-drug conjugates (ADCs) of N,N-dialkylauristatins directed against the target epidermal growth factor receptor (EGFR, gene ID 1956), effective metabolites of these ADCs, methods for producing these ADCs, use of these ADCs for treatment and or prevention of diseases as well as the use of these ADCs to produce pharmaceutical drugs for treatment and/or prevention of diseases, in particular hyperproliferative and/or angiogenic diseases such as cancer, for example. Such treatments may be administered as monotherapy or in combination with other pharmaceutical drugs or other therapeutic measures.