WO2022264114A3 - Ros sensitive diazaborines for the construction of stimuli-responsive bioconjugates - Google Patents

Ros sensitive diazaborines for the construction of stimuli-responsive bioconjugates Download PDF

Info

Publication number
WO2022264114A3
WO2022264114A3 PCT/IB2022/055675 IB2022055675W WO2022264114A3 WO 2022264114 A3 WO2022264114 A3 WO 2022264114A3 IB 2022055675 W IB2022055675 W IB 2022055675W WO 2022264114 A3 WO2022264114 A3 WO 2022264114A3
Authority
WO
WIPO (PCT)
Prior art keywords
ros
diazaborines
dab
responsive
ability
Prior art date
Application number
PCT/IB2022/055675
Other languages
French (fr)
Other versions
WO2022264114A2 (en
Inventor
Pedro GÓIS
João ANTÓNIO
Joana CARVALHO
Original Assignee
Technophage, Investigação E Desenvolvimento Em Biotechnologia, S.A.
Faculdade De Farmácia Da Universidade De Lisboa
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Technophage, Investigação E Desenvolvimento Em Biotechnologia, S.A., Faculdade De Farmácia Da Universidade De Lisboa filed Critical Technophage, Investigação E Desenvolvimento Em Biotechnologia, S.A.
Publication of WO2022264114A2 publication Critical patent/WO2022264114A2/en
Publication of WO2022264114A3 publication Critical patent/WO2022264114A3/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
    • C07F5/02—Boron compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
    • C07F5/02—Boron compounds
    • C07F5/025—Boronic and borinic acid compounds

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Pulmonology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention described herein provides a reactive oxygen species (ROS) responsive linker based on diazaborines (DAB) scaffold. Here we show the ability of diazaborines (DABs) scaffolds to be stable in different biocompatible conditions (pH 4.5, 7.4 and 9; plasma) over 14 days, retaining the ability to be rapidly oxidized by hydrogen peroxide. The ROS-sensitive unit, DAB, was tuned to attach the cytotoxic/ targeting unit to 2-FPBA component or hydrazine part. We describe the first ROS-responsive antibody-drug conjugates (ADCs), containing DAB linkers, stable in physiological conditions and activated in the presence of hydrogen peroxide. The targeting drug conjugate incorporates the cytotoxic drug SN-38 and exhibits a high selectivity for B-cell lymphoma CLBL-1 cell line and an IC50 in the nanomolar range.
PCT/IB2022/055675 2021-06-18 2022-06-18 Ros sensitive diazaborines for the construction of stimuli-responsive bioconjugates WO2022264114A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
PT11729821 2021-06-18
PT117298 2021-06-18

Publications (2)

Publication Number Publication Date
WO2022264114A2 WO2022264114A2 (en) 2022-12-22
WO2022264114A3 true WO2022264114A3 (en) 2023-02-23

Family

ID=82786477

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2022/055675 WO2022264114A2 (en) 2021-06-18 2022-06-18 Ros sensitive diazaborines for the construction of stimuli-responsive bioconjugates

Country Status (1)

Country Link
WO (1) WO2022264114A2 (en)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6248305B1 (en) * 1999-01-25 2001-06-19 Sri International Boron heterocycle steroid mimics and associated pharmaceutical compositions and methods of use
WO2022040157A1 (en) * 2020-08-18 2022-02-24 5Metis, Inc. Boron containing compounds and their uses

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6248305B1 (en) * 1999-01-25 2001-06-19 Sri International Boron heterocycle steroid mimics and associated pharmaceutical compositions and methods of use
WO2022040157A1 (en) * 2020-08-18 2022-02-24 5Metis, Inc. Boron containing compounds and their uses

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
DAVIS M C ET AL: "Syntheses and evaluation of benzodiazaborine compounds against M. tuberculosis H"3"7R"V in vitro", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, ELSEVIER, AMSTERDAM NL, vol. 8, no. 7, 7 April 1998 (1998-04-07), pages 843 - 846, XP004136976, ISSN: 0960-894X, DOI: 10.1016/S0960-894X(98)00126-7 *
GROZIAK MICHAEL P. ET AL: "Planar Boron Heterocycles with Nucleic Acid-Like Hydrogen-Bonding Motifs", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 119, no. 33, 1 August 1997 (1997-08-01), pages 7817 - 7826, XP055901828, ISSN: 0002-7863, DOI: 10.1021/ja963784i *
STRESS CEDRIC J. ET AL: "Comparison of boron-assisted oxime and hydrazone formations leads to the discovery of a fluorogenic variant", ORGANIC & BIOMOLECULAR CHEMISTRY, vol. 14, no. 24, 1 January 2016 (2016-01-01), pages 5529 - 5533, XP055980971, ISSN: 1477-0520, DOI: 10.1039/C6OB00168H *

Also Published As

Publication number Publication date
WO2022264114A2 (en) 2022-12-22

Similar Documents

Publication Publication Date Title
Jeffrey et al. Dipeptide-based highly potent doxorubicin antibody conjugates
Flygare et al. Antibody‐drug conjugates for the treatment of cancer
WO2001047572A3 (en) Device and active component for inhibiting formation of thrombus-inflammatory cell matrix
MX2023013118A (en) Exatecan derivatives and antibody-drug conjugates thereof.
PH12021550692A1 (en) Conjugation linkers containing 2,3-diaminosuccinyl group
WO2005112919A8 (en) Self-immolative linkers and drug conjugates
HUP0203123A2 (en) Process for preparation of polyglutamate-therapeutic agent conjugates
AU2001288829A1 (en) Degradable polyacetal polymers
CY1115289T1 (en) Methods of Treatment Against Inflammation-Related Illness
WO2009142719A3 (en) Tympanic membrane permeating ear drops and uses thereof
EP1183538A4 (en) Cyclodextrin polymers for use as drug carriers
WO2007037874A3 (en) Methods for treatment and prevention of otitis media using chemical penetration enhancers to facilitate transmembrane drug delivery into the middle ear
WO2001085212A3 (en) Drug delivery systems for photodynamic therapy
WO2018124512A3 (en) Aptamer-drug conjugate and use thereof
WO2007048219A3 (en) Sustained drug release composition
MX9602656A (en) Transdermal device containing polyvinylpyrrolidone as solubility enhancer.
EP1478406A4 (en) Compositions for delivery of therapeutics and other materials, and methods of making and using the same
PT1165566E (en) PYRIDINE AND PYRIMIDINE DERIVATIVES AND THEIR USE AS INHIBITORS OF CYTOKIN ASSOCIATED DISEASES
MY161620A (en) Oral care formulations that enhance amount of soluble zinc
WO2007106554A3 (en) Treatment and prevention of vascular hyperplasia using polyamine and polyamine analog compounds
MX2020013832A (en) Binder-drug conjugates directed against cxcr5, having enzymatically cleavable linkers and improved activity profile.
WO2022264114A3 (en) Ros sensitive diazaborines for the construction of stimuli-responsive bioconjugates
WO2006076097A3 (en) Stable non-crystalline formulation comprising losartan
MX2023003448A (en) Pharmaceutical composition comprising antibody-drug conjugate, and use of pharmaceutical composition.
WO2002024157A3 (en) Acryl adhesive useful in transdermal drug delivery systems

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 22750893

Country of ref document: EP

Kind code of ref document: A2

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 22750893

Country of ref document: EP

Kind code of ref document: A2