1430738-35-4Relevant academic research and scientific papers
Design and Synthesis of Tesirine, a Clinical Antibody-Drug Conjugate Pyrrolobenzodiazepine Dimer Payload
Tiberghien, Arnaud C.,Levy, Jean-Noel,Masterson, Luke A.,Patel, Neki V.,Adams, Lauren R.,Corbett, Simon,Williams, David G.,Hartley, John A.,Howard, Philip W.
, p. 983 - 987 (2016)
Pyrrolobenzodiazepine dimers are an emerging class of warhead in the field of antibody-drug conjugates (ADCs). Tesirine (SG3249) was designed to combine potent antitumor activity with desirable physicochemical properties such as favorable hydrophobicity a
Scale-up Synthesis of Tesirine
Tiberghien, Arnaud C.,Von Bulow, Christina,Barry, Conor,Ge, Huajun,Noti, Christian,Collet Leiris, Florence,McCormick, Marc,Howard, Philip W.,Parker, Jeremy S.
, p. 1241 - 1256 (2018/09/06)
This work describes the enabling synthesis of tesirine, a pyrrolobenzodiazepine antibody-drug conjugate drug-linker. Over the course of four synthetic campaigns, the discovery route was developed and scaled up to provide a robust manufacturing process. Early intermediates were produced on a kilogram scale and at high purity, without chromatography. Midstage reactions were optimized to minimize impurity formation. Late stage material was produced and purified using a small number of key high-pressure chromatography steps, ultimately resulting in a 169 g batch after 34 steps. At the time of writing, tesirine is the drug-linker component of eight antibody-drug conjugates in multiple clinical trials, four of them pivotal.
PYRROLOBENZODIAZEPINE-ANTIBODY CONJUGATES
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Page/Page column 78, (2015/04/28)
Conjugates of specific PBD dimers with an antibody that binds to CD22, the antibody comprising a VH domain having the sequence according to SEQ ID NO. 1.
ANTIBODIES AND ANTIBODY-DRUG CONJUGATES
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Paragraph 0519, (2015/11/03)
This application provides antibodies and antigen binding fragments thereof which are capable of specifically binding the 5T4 cell surface antigen, antibody-drug conjugates, and antibody-imaging agent conjugates, as well as means and methods for producing and using them.
NOVEL ANTIBODY CONJUGATES AND USES THEREOF
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Page/Page column 152; 153, (2014/09/03)
Provided are novel antibody drug conjugates (ADCs), and methods of using such ADCs to treat proliferative disorders.
AXL ANTIBODY-DRUG CONJUGATE AND ITS USE FOR THE TREATMENT OF CANCER
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Page/Page column 109, (2014/11/13)
The present invention relates to an antibody-drug conjugate capable of binding to the protein Axl. From one aspect, the invention relates to an antibody-drug conjugate comprising an antibody capable of binding to Axl, said antibody being conjugated to at least one drug which is a pyrrolobenzodiazepme dimer (PBD dimer) drug. The invention also comprises method of treatment and the use of said antibody-drug conjugate for the treatment of cancer.
SYNTHESIS METHOD AND INTERMEDIATES USEFUL IN THE PREPARATION OF PYRROLOBENZODIAZEPINES
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Page/Page column 79, (2013/04/25)
A compound of formula I wherein: R7 is selected from: ORA, where RA is selected from C1-4 saturated alkyl, optionally substituted by phenyl, which may bear a chloro substituent, pyridyl and furanyl; chloro; NH2; -CH2-O-C(=O)Me; R8 is OProt°, where Prot° is a silicon-based oxygen protecting group orthogonal to Rc; R9 is selected from H, methyl and methoxy; Rs is selected from CF3, (CF2)3CF3, CH3 and (formula 2) and Rc is selected from: (i) -C(=O)-ORC1, where RC1 is a saturated C1-4 alkyl group; (ii) -CH2-O-C(=0)RC2, where RC2 is methyl or phenyl; (iii) -CH2-O-Si-(RSi1)(RSi2)(RSi3), where RSi1, RSi2, RSi3 are independently selected from C1-6 a saturated alkyl group and a phenyl group; and (iv) -C(-YRC3)(-YRC4) where each Y is independently O or S, and where RC3 and RC4 are independently a saturated C1-4 alkyl group, or together form a C2-3 alkylene.
