WO2022264114A3 - Ros sensitive diazaborines for the construction of stimuli-responsive bioconjugates - Google Patents
Ros sensitive diazaborines for the construction of stimuli-responsive bioconjugates Download PDFInfo
- 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
Links
- MRGWUDKEBPXDJX-UHFFFAOYSA-N diazaborinine Chemical class B1=CC=CN=N1 MRGWUDKEBPXDJX-UHFFFAOYSA-N 0.000 title abstract 3
- 238000010276 construction Methods 0.000 title 1
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 abstract 4
- 239000003642 reactive oxygen metabolite Substances 0.000 abstract 4
- 239000000611 antibody drug conjugate Substances 0.000 abstract 2
- 229940049595 antibody-drug conjugate Drugs 0.000 abstract 2
- 230000008685 targeting Effects 0.000 abstract 2
- DGUWACLYDSWXRZ-UHFFFAOYSA-N (2-formylphenyl)boronic acid Chemical compound OB(O)C1=CC=CC=C1C=O DGUWACLYDSWXRZ-UHFFFAOYSA-N 0.000 abstract 1
- 208000003950 B-cell lymphoma Diseases 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 abstract 1
- 239000000562 conjugate Substances 0.000 abstract 1
- 231100000433 cytotoxic Toxicity 0.000 abstract 1
- 229940127089 cytotoxic agent Drugs 0.000 abstract 1
- 239000002254 cytotoxic agent Substances 0.000 abstract 1
- 230000001472 cytotoxic effect Effects 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine group Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 abstract 1
- 230000004962 physiological condition Effects 0.000 abstract 1
Classifications
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- 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.
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)
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 |
-
2022
- 2022-06-18 WO PCT/IB2022/055675 patent/WO2022264114A2/en active Application Filing
Patent Citations (2)
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)
Title |
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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 |
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