870487-08-4

Usage

Uses

Used in Pharmaceutical Industry:
Boc-Val-Cit is used as a cleavable ADC linker for targeted cancer therapy. Its unique structure allows for the specific cleavage of the Val-Cit part by Cathepsin B, an enzyme overexpressed in various cancer cells. This selective cleavage enables the release of the drug payload in the tumor microenvironment, increasing the therapeutic efficacy and reducing side effects.
Used in Drug Delivery Systems:
Boc-Val-Cit is also used in the development of drug delivery systems for improved cancer treatment. Its ability to be cleaved under specific conditions allows for the controlled release of the drug payload, enhancing the bioavailability and therapeutic outcomes. Additionally, the Boc group can be removed under acidic conditions, further enhancing the drug's activity in the tumor microenvironment.

Upstream product

• 3392-12-9 Boc-Val-ONSu 
• 372-75-8 Citrulline 
• 13734-41-3 t-Boc-L-valine 
• 133174-15-9 (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-5-ureidopentanoic acid 
• 93964-78-4 methyl (S)-2-amino-5-ureidopentanoate hydrochloride 
• 60-29-7 diethyl ether 
• 77-92-9 citric acid 

Downstream Products

• 1609075-21-9 N-((tert-butoxy)carbonyl)-L-valyl-N-{[1-(2-{[(4S)-10-bromo-4-ethyl-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-4-yl]oxy}-2-oxoethyl)cyclohexyl]methyl}-N⁵-carbamoyl-L-ornithinamide 
• 870487-10-8 tert-butyl ((5)-3-methyl-1-(((5)-1-((4-((((4-nitrophenoxy)carbonyl)oxy)methyl)phenyl)amino)-1-oxo-5-ureidopentan-2-yl)amino)-1-oxobutan-2-yl)carbamate 
• 1615234-88-2 C₂₉H₄₇N₇O₇ 
• 1615234-91-7 C₃₆H₅₀N₈O₁₁ 
• 1037795-34-8 Boc-L-valine-L-citrulline-p-aminobenzoic acid t-butyl ester 

Relevant academic research and scientific papers

Design and Development of Glucocorticoid Receptor Modulators as Immunology Antibody-Drug Conjugate Payloads

Glucocorticoid receptor modulators (GRM) are the first-line treatment for many immune diseases, but unwanted side effects restrict chronic dosing. However, targeted delivery of a GRM payload via an immunology antibody-drug conjugate (iADC) may deliver significant efficacy at doses that do not lead to unwanted side effects. We initiated our α-TNF-GRM ADC project focusing on identifying the optimal payload and a linker that afforded stable attachment to both the payload and antibody, resulting in the identification of the synthetically accessible maleimide-Gly-Ala-Ala linker. DAR 4 purified ADCs were shown to be more efficacious in a mouse contact hypersensitivity model than the parent α-TNF antibody. Analysis of P1NP and corticosterone biomarkers showed there was a sufficient therapeutic window between efficacy and unwanted effects. In a chronic mouse arthritis model, α-TNF-GRM ADCs were more efficacious than both the parent α-TNF mAb and an isotype control bearing the same GRM payload.

TREATMENT OF DISEASES CHARACTERIZED BY OVEREXPRESSION OF A HEPATOCELLULAR RECEPTOR A2 PRODUCING ERYTHROPOIETIN (EPHA2)

The present invention relates to a Bicycle toxin conjugate BT5528, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof, and uses thereof.

An optimal “Click” formulation strategy for antibody-drug conjugate synthesis

As a versatile reaction for bioconjugation, Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) has enormous potential in the synthesis of antibody-drug conjugates (ADCs). In order to optimize CuAAC-based ADC synthesis, we characterized kinetically different formulation processes by mimicking ADC synthesis using small molecules and subsequently revealed unique kinetic behaviors of different combinations of alkyne and azide conditions. Our results indicate that under ADC synthesis conditions, for an alkyne-containing drug, its concentration has minimal impact on the reaction rate when an antibody has a non-metal-chelating azide but is proportional to concentration when an antibody contains a metal-chelating azide; however, for an alkyne-containing antibody, the ADC synthesis rate is proportional to the concentration of a drug with a non-metal-chelating azide but displays almost no dependence on drug concentration with a metal-chelating azide. Based on our results, we designed and tested an optimal “click” formulation strategy that allowed rapid and cost-effective synthesis of a new ADC.

BICYCLE TOXIN CONJUGATES AND USES THEREOF

The present invention relates to Bicycle toxin conjugates, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof, and uses thereof for preventing or treating a disease, disorder, or condition characterised by overexpression

The antibody-drug conjugate hemiasterlin derivatives and their pharmaceutically (by machine translation)

[Problem] to give one specific target cell cytotoxic, normal cells to the cytotoxic is suppressed, the antibody-drug conjugate medicine hemiasterlin derivatives. (2) Formula [a]:[In the formula, mAb antibody expressed, q is 1 - 8 represents an integer of, h are 1 - 5 represents an integer of, g is an alanine residue (Ala) to represent, g is 1 - 4 represents an integer of, Y is a single bond or a formula (Y-a 1) is represented by the group, Z is formula (Z-a 1), equation (Z-a 2), equation (Z-a 3), formula (Z-a 4), formula (Z-a 5), type (Z-a 6), formula (Za-a 1), equation (Za-in 2), equation (Za-a 3), formula (Za-a 4), formula (Za-a 5), type (Za d 6), formula (Za-a 7), type (Za-in 8), or a group represented by formula (Za-a 10) (Za-a 9) formula a] is expressed by, antibody-drug conjugate or its pharmaceutically acceptable salt containing a drug. [Drawing] no (by machine translation)

Conjugate of cytotoxin molecule and cell binding receptor molecule

A conjugate of a strong cytotoxin molecule and a cell binding receptor molecule has a structure shown in a molecular formula (I), wherein T, L, m, n, -----, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12 and R13 are defined in the text. The conjugate is used for treating cancer, immunological diseases and infectious diseases.

CALICHEAMICIN DERIVATIVES AND ANTIBODY DRUG CONJUGATES THEREOF

The present invention is directed to novel calicheamicin derivatives useful as payloads in antibody-drug-conjugates (ADC's), and to payload-linker compounds and ADC compounds comprising the same; to pharmaceutical compositions comprising the same and to methods for using the same to treat pathological conditions such as cancer.

PYRROLOBENZODIAZEPINES AND CONJUGATES THEREOF

Conjugates and compounds for making conjugates which are PBD molecules linked via the N10 position are disclosed, along with the use of the conjugates for treating proliferative diseases, including cancer.

CONJUGATE OF CELL-BINDING RECEPTOR WITH CYTOTOXIC AGENT

PROBLEM TO BE SOLVED: To provide a conjugate of a potent cytotoxic agent with a cell-surface receptor binding molecule for targeted treatment. SOLUTION: According to the present invention, there is provided a conjugate having a structure of formula (I) and a pharmaceutical acceptable salt and a solvate thereof. The conjugate is used for treating cancer, autoimmune disease, and infectious disease. (T is a targeting or binding ligand; L is a releasable linker; a broken line is a linkage bond that L connects to a molecule inside the bracket independently; n is an integer of 1 to 20; m is an integer of 1 to 10; and a structure in parentheses is a potent antimitotic agent/drug.) SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT

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.