1343407-91-9Relevant academic research and scientific papers
CROSS-LINKED PYRROLOBENZODIAZEPINE DIMER (PBD) DERIVATIVE AND ITS CONJUGATES
-
Page/Page column 161, (2020/01/31)
A novel cross-linked cytotoxic agents, pyrrolobenzo-diazepine dimer (PBD) derivatives, and their conjugates to a cell-binding molecule, a method for preparation of the conjugates and the therapeutic use of the conjugates.
CONJUGATION LINKERS CONTAINING 2,3-DIAMINOSUCCINYL GROUP
-
Page/Page column 306-307, (2020/05/19)
Provided is a conjugate of a cytotoxic drug/molecule to a cell-binding molecule with a bis-linker (adual-linker) containing a 2, 3-diaminosuccinyl group. It also relates to preparation of the conjugate of a cytotoxic drug/molecule to a cell-binding molecule with the bis-linker, particularly when the drug having functional groups of amino, hydroxyl, diamino, amino-hydroxyl, dihydroxyl, carboxyl, hydrazine, aldehyde and thiol for conjugation with the bis-linker in a specific manner, as well as the therapeutic use of the conjugates.
ISOQUINOLIDINOBENZODIAZEPINE (IQB)-1(CHLOROMETHYL)-2,3-DIHYDRO-1H-BENZO[E]INDOLE (CBI) DIMERS
-
, (2018/04/27)
Provided herein are isoquinolidinobenzodiazepine (IQB)-1(chloromethyl)-2,3-dihydro-1H-benzo[e]indole (CBI) dimers, antibody-drug conjugates comprising them and methods of use for killing cells and treating disease.
PYRROLOBENZODIAZEPINES AND CONJUGATES THEREOF
-
Paragraph 1159; 1160, (2018/05/26)
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.
PYRROLOBENZODIAZEPINE CONJUGATES
-
Page/Page column 142; 143; 144, (2018/04/27)
A compound of formula (I) : (I) and its conjugates.
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 CONJUGATES
-
Page/Page column 104, (2017/09/05)
A conjugate of formula (I), wherein L is a Ligand unit, D is a Drug Linker unit of formula (II), wherein either: (a) R10 and R11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound; or (b)
PYRROLOBENZODIAZEPINE ANTI-HER2 ANTIBODY CONJUGATES
-
Page/Page column 41; 42, (2017/09/07)
A conjugate of formula (I) L - (DL)p (I) wherein L is an antibody (Ab) which binds HER2, D is a Drug Linker unit of formula (A) wherein p is an integer of from 1 to 20.
Synthesis and in vitro evaluation of SG3227, a pyrrolobenzodiazepine dimer antibody-drug conjugate payload based on sibiromycin
Kemp, Gary C.,Tiberghien, Arnaud C.,Patel, Neki V.,D'Hooge, Francois,Nilapwar, Sanjay M.,Adams, Lauren R.,Corbett, Simon,Williams, David G.,Hartley, John A.,Howard, Philip W.
, p. 1154 - 1158 (2017/06/21)
A novel pyrrolobenzodiazepine dimer payload, SG3227, was rationally designed based on the naturally occurring antitumour compound sibiromycin. SG3227 was synthesized from a dimeric core in an efficient fashion. An unexpected room temperature Diels-Alder reaction occurred during the final step of the synthesis and was circumvented by use of an iodoacetamide conjugation moiety in place of a maleimide. The payload was successfully conjugated to trastuzumab and the resulting ADC exhibited potent activity against a HER2-expressing human cancer cell line in vitro.
ANTIBODIES AND ANTIBODY-DRUG CONJUGATES
-
Paragraph 0533, (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.
