Delving into the Latest Updates on Anti-HER2 monoclonal antibody-MCC-DM1 conjugate(Shanghai Jiaolian Drug Development Co. Ltd.) with Synapse

Overview

Basic Info

Drug Type

Antibody drug conjugate (ADC)

Synonyms

恩美曲妥珠单抗-B003

Target

HER2 x Tubulin

Mechanism

HER2 antagonists(Receptor protein-tyrosine kinase erbB-2 antagonists), Tubulin inhibitors

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal Diseases

Active Indication

Breast CancerHER2 Positive Breast Cancer

Inactive Indication-

Originator Organization

Shanghai Jiaolian Drug Development Co. Ltd.

Active Organization

Shanghai Jiaolian Drug Development Co. Ltd.

Inactive Organization

Shanghai Pharmaceuticals Holding Co., Ltd.

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC35H48ClN3O10S

InChIKeyANZJBCHSOXCCRQ-FKUXLPTCSA-N

CAS Registry139504-50-0

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Gene Sequence

Sequence Code 18481L

The sequence is quoted from: *****

Sequence Code 44772H

The sequence is quoted from: *****

主要研究目的：评估B003在HER2阳性的转移或复发性乳腺癌患者中的剂量限制性毒性（DLT）和最大耐受剂量（MTD）；评估B003在HER2阳性的转移或复发性乳腺癌患者中的安全性和耐受性。次要研究目的：评估B003在HER2阳性的转移或复发性乳腺癌患者中的药代动力学特征，免疫原性，初步疗效，确定B003在后期研究中的推荐剂量。

[Translation]

Primary study objectives: To evaluate the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of B003 in patients with HER2-positive metastatic or recurrent breast cancer; To evaluate the safety and tolerability of B003 in patients with HER2-positive metastatic or recurrent breast cancer. Secondary study objectives: To evaluate the pharmacokinetic characteristics, immunogenicity, and preliminary efficacy of B003 in patients with HER2-positive metastatic or recurrent breast cancer, and to determine the recommended dose of B003 in later studies.

Start Date27 Mar 2019

Sponsor / Collaborator

Shanghai Jiaolian Drug Development Co. Ltd.

[+1]

JPRN-UMIN000025777 / Completed

A study to evaluate the exposure to selected smoke constituents in healthy smokers using B-003 for 5 days confined in a hospital - A study to evaluate the exposure to selected smoke constituents when using B-003

Start Date21 Jan 2017

Sponsor / Collaborator

Japan Tobacco, Inc.

100 Clinical Results associated with Anti-HER2 monoclonal antibody-MCC-DM1 conjugate(Shanghai Jiaolian Drug Development Co. Ltd.)

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100 Translational Medicine associated with Anti-HER2 monoclonal antibody-MCC-DM1 conjugate(Shanghai Jiaolian Drug Development Co. Ltd.)

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100 Patents (Medical) associated with Anti-HER2 monoclonal antibody-MCC-DM1 conjugate(Shanghai Jiaolian Drug Development Co. Ltd.)

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5

Literatures (Medical) associated with Anti-HER2 monoclonal antibody-MCC-DM1 conjugate(Shanghai Jiaolian Drug Development Co. Ltd.)

04 Jul 2018·Nutrition and CancerQ4 · MEDICINE

Transglutaminase 2 Mediates the Cytotoxicity of Resveratrol in a Human Cholangiocarcinoma and Gallbladder Cancer Cell Lines

Q4 · MEDICINE

Article

Author: Scricciolo, Alice ; Braidotti, Paola ; Tacchini, Lorenza ; Vaira, Valentina ; Doneda, Luisa ; Tosi, Delfina ; Elli, Luca ; Roncoroni, Leda ; Lombardo, Vincenza ; Branchi, Federica

Resveratrol is a polyphenolic compound extracted from plants and is also a constituent of red wine. Our aim was to evaluate if the cytotoxic effect of resveratrol (RES) on cholangiocarcinoma (CC) and gallbladder cancer (GBC) cell lines could be abolished by TG2 inhibition. Human CC and GBC cell lines (SK-ChA-1 and MZ-ChA-1), grown in a three-dimensional cell culture system (MCTS, multicellular tumor spheroids), were treated for 72 h with RES (32, 64 µM) alone or combined with different TG2 inhibitors (Cystamine, B003, T101). We investigated: cells viability; cell morphology with light microscopy (LM) and transmission electron microscopy (TEM); immunoreactivity with immunohistochemistry; Q-Banding karyotype analysis; TG2 activity; Western blotting. RES treatment induced a significant inhibition of cell growth, ranging from 24% to 76% in both cell lines. The inhibitors successfully reduced TG2 activity without any variation of protein quantity as demonstrated by immunohistochemistry and Western blot. TG2 inhibition resulted in cell growth normalization. In addition, morphologic analysis by light and transmission electron microscopy confirmed the cytotoxic effect of RES and its reduction consequent to TG2 inhibition. Our data demonstrated a connection between the cytotoxic effect of RES in SK-ChA-1 and MZ-ChA-1 and TG2 activity.

01 Sep 2015·Drug Metabolism and DispositionQ2 · MEDICINE

Intracellular Catabolism of an Antibody Drug Conjugate with a Noncleavable Linker

Q2 · MEDICINE

Article

Author: Fanslow, William C ; Rock, Brooke M ; Hamblett, Kevin J ; Tometsko, Mark E ; Patel, Sonal K ; Rock, Dan A

Antibody drug conjugates are emerging as a powerful class of antitumor agents with efficacy across a range of cancers; therefore, understanding the disposition of this class of therapeutic is crucial. Reported here is a method of enriching a specific organelle (lysosome) to understand the catabolism of an anti-CD70 Ab-MCC-DM1, an antibody drug conjugate with a noncleavable linker. With such techniques a higher degree of concentration-activity relationship can be established for in vitro cell lines; this can aid in understanding the resultant catabolite concentrations necessary to exert activity.

01 Jun 2011·Neurochemistry InternationalQ3 · MEDICINE

Blockade of enzyme activity inhibits tissue transglutaminase-mediated transamidation of α-synuclein in a cellular model of Parkinson's disease

Q3 · MEDICINE

Article

Author: Melanie Gerard ; Benjamin Drukarch ; Micha M.M. Wilhelmus ; Cornelis A.M. Jongenelen ; Anne-Marie Van Dam ; Robin Verhaar ; Veerle Baekelandt

Transamidation of α-synuclein by the Ca(2+)-dependent enzyme tissue transglutaminase (tTG, EC 2.3.2.13) is implicated in Parkinson's disease (PD). tTG may therefore offer a novel therapeutic target to intervene in PD. Here we first evaluated the potency and efficacy of three recently developed irreversible active-site inhibitors of tTG (B003, Z006 and KCC009) to inhibit tTG activity in vitro and in living cells. In vitro, all compounds were found to be full inhibitors of tTG activity showing a rank order of potency (defined by IC-50 values) of Z006>B003>KCC009. Upon Ca(2+) ionophore (A23187) induced activation of cellular tTG (measured by incorporation of the tTG-specific amine substrate 5-(biotinamido)pentylamine (BAP) into cellular proteins) in neuroblastoma SH-SY5Y cells, only Z006 (0.3-30 μM) retained the capacity to completely inhibit tTG activity. Under these conditions B003 (3-300 μM) only partially blocked tTG activity whereas KCC009 (3-100 μM) failed to affect tTG activity at any of the concentrations used. Z006 (30 μM) also blocked the tTG mediated incorporation of BAP into α-synuclein monomers and SDS-resistant multimers in vitro and in α-synuclein overexpressing SHSY5Y cells exposed to A23187 or the PD mimetic 1-methyl-4-phenylpyridine (MPP(+)). Moreover, Z006 (30 μM) substantially reduced formation of SDS-resistant α-synuclein multimers in SH-SY5Y cells exposed to A23187 or MPP(+) in the absence of BAP. We conclude that α-synuclein is a cellular substrate for tTG under conditions mimicking PD and blockade of tTG activity counteracts α-synuclein transamidation and aggregation in vitro and in living cells. Moreover, our cell model appears an excellent readout to identify candidate inhibitors of intracellular tTG.

100 Deals associated with Anti-HER2 monoclonal antibody-MCC-DM1 conjugate(Shanghai Jiaolian Drug Development Co. Ltd.)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Breast Cancer	Phase 2	CN	Shanghai Jiaolian Drug Development Co. Ltd.	16 Nov 2022
HER2 Positive Breast Cancer	Phase 1	CN	Shanghai Jiaolian Drug Development Co. Ltd.	27 Mar 2019
Breast Cancer	Preclinical	CN	Shanghai Pharmaceuticals Holding Co., Ltd.	16 Nov 2022
HER2 Positive Breast Cancer	Preclinical	CN	Shanghai Pharmaceuticals Holding Co., Ltd.	27 Mar 2019