382137-65-7Relevant academic research and scientific papers
Pyrrolobenzodiazepine Dimer Antibody-Drug Conjugates: Synthesis and Evaluation of Noncleavable Drug-Linkers
Gregson, Stephen J.,Masterson, Luke A.,Wei, Binqing,Pillow, Thomas H.,Spencer, Susan D.,Kang, Gyoung-Dong,Yu, Shang-Fan,Raab, Helga,Lau, Jeffrey,Li, Guangmin,Lewis Phillips, Gail D.,Gunzner-Toste, Janet,Safina, Brian S.,Ohri, Rachana,Darwish, Martine,Kozak, Katherine R.,Dela Cruz-Chuh, Josefa,Polson, Andrew,Flygare, John A.,Howard, Philip W.
, p. 9490 - 9507 (2017/12/26)
Three rationally designed pyrrolobenzodiazepine (PBD) drug-linkers have been synthesized via intermediate 19 for use in antibody-drug conjugates (ADCs). They lack a cleavable trigger in the linker and consist of a maleimide for cysteine antibody conjugation, a hydrophilic spacer, and either an alkyne (6), triazole (7), or piperazine (8) link to the PBD. In vitro IC50 values were 11-48 ng/mL in HER2 3+ SK-BR-3 and KPL-4 (7 inactive) for the anti-HER2 ADCs (HER2 0 MCF7, all inactive) and 0.10-1.73 μg/mL (7 inactive) in CD22 3+ BJAB and WSU-DLCL2 for anti-CD22 ADCs (CD22 0 Jurkat, all inactive at low doses). In vivo antitumor efficacy for the anti-HER2 ADCs in Founder 5 was observed with tumor stasis at 0.5-1 mg/kg, 1 mg/kg, and 3-6 mg/kg for 6, 8, and 7, respectively. Tumor stasis at 2 mg/kg was observed for anti-CD22 6 in WSU-DLCL2. In summary, noncleavable PBD-ADCs exhibit potent activity, particularly in HER2 models.
Synthesis of bis-1,2,3-triazolo-bridged unsymmetrical pyrrolobenzodiazepine trimers via 'click' chemistry and their DNA-binding studies
Kamal, Ahmed,Shankaraiah, Nagula,Reddy, Ch.Ratna,Prabhakar,Markandeya, Nagula,Srivastava, Hemant Kumar,Sastry, G.Narahari
experimental part, p. 5498 - 5506 (2010/08/06)
New conceivable synthetic approach for the construction of nitrogen-rich 1,2,3-triazolo-pyrrolo[2,1-c] [1,4]benzodiazepine (TPBD, 3ac) trimers has been developed.The first example of a bis-1,2,3-triazolo-bridged unsymmetrical PBD trimer has been successfully synthesized by employing a CuAAC type 'click' chemistry protocol.This efficient route generates tri-imine functionality in a single molecule.It has been envisaged that such tri-imine functionalities could bring in efficient interaction with DNA in a sequence-selective manner in the minor groove of duplex DNA.One of the representative analogues 3c has shown improved DNA-binding ability (DTm 23.7 °C) by thermal denaturation studies using CT-DNA and this data is also supported by molecular modeling (MD) studies.
PYRROLOBENZODIAZEPINES
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Page/Page column 82-83, (2008/06/13)
Compounds and a method of synthesis of compounds of formula (Ia) or (Ib): and salts, solvates, and chemically protected forms thereof, wherein the dotted lines indicate the optional presence of a double bond between C1 and C2 or C2 and C3; R2 a
Synthesis and DNA binding affinity of novel A-C8/C-C2-exo unsaturated alkoxyamido-linked pyrrolo[2,1-c][1,4]benzodiazepine dimers.
Kamal, Ahmed,Srinivas,Ramulu,Ramesh,Kumar, P Praveen,Kumar, M Shiva
, p. 4337 - 4350 (2007/10/03)
The synthesis of novel A-C8/C-C2-exo unsaturated alkoxyamido-linked pyrrolo[2,1-c][1,4]benzodiazepine dimers is reported and these dimers show significant DNA binding affinity and they also exhibit moderate anticancer activity.
Synthesis of novel C2 and C2-C8 linked pyrrolo[2,1-c][1,4]benzodiazepine-naphthalimide hybrids as DNA-binding agents
Kamal, Ahmed,Srinivas,Ramulu,Ramesh,Kumar, P. Praveen
, p. 3577 - 3581 (2007/10/03)
Synthesis of C2 and C2-C8 linked pyrrolobenzodiazepine-naphthalimide hybrids have been prepared that exhibit significant DNA-binding affinity and cytotoxicity.
Synthesis and DNA-binding affinity of A-C8/C-C2 alkoxyamido-linked pyrrolo[2,1-c][1,4]benzodiazepine dimers
Kamal, Ahmed,Ramulu,Srinivas,Ramesh
, p. 3955 - 3958 (2007/10/03)
The synthesis of new A-C8/C-C2 alkoxyamido-linked pyrrolo[2,1-c][1,4]- benzodiazepine dimers have been described in this report. These dimers exhibit significant DNA-binding ability with moderate anticancer activity.
