Glycan-modified nucleic acids, methods of preparation, and therapeutic uses

Fantastic chemistry making glyconucleic acids, such as glycoRNA and glycoDNA using the now world-famous click chemistry to treat diseases such as inflammation disorder, an autoimmune disease, cancer, metabolic disease, clotting disease, anti-clotting disease, allergy, viral disease, and microbial infection.
Ryan FlynnCiaran LawlorNamita Bisaria, Ph.D.Richard CummingsCarolyn Bertozzi et al

See the full patent on Espacenet.

First-in-Class Small Molecule Drug Approvals of 2022

First-in-Class Small Molecule Drug Approvals of 2022
Great collection by Drug Hunter.

Of the 36 novel small-molecule and large-molecule drugs approved by the FDA in 2022, 18 were first-in-class approvals, including 9 small molecules (excluding atoms).

Some of the notable small molecule first-in-class approvals of 2022 include:
Sunlenca (lenacapavir): the first approved drug targeting HIV-1 capsid, indicated for multi-drug resistant HIV with an impressive bi-annual dosing regimen (Gilead Sciences)

Sotyktu (deucravacitinib): the first approved de novo deuterated drug – an oral, allosteric tyrosine kinase 2 (TYK2) inhibitor for moderate-to-severe plaque psoriasis (Bristol Myers Squibb)

Ztalmy (ganaxolone): the first neurosteroid to be studied for epilepsy, approved for treating seizures in cyclin-dependent kinase-like 5 deficiency disorder, an oral GABA-A receptor modulator (Marinus Pharma) – a cyclodextrin-enabled formulation

Pyrukynd (mitapivat): the first approved therapeutic for pyruvate kinase (PK) deficiency – an oral pyruvate kinase activator that improves hemolytic anemia (Agios Pharmaceuticals)

Voquezna (vonoprazan): the first potassium-competitive acid blocker that acts via reversible potassium-competitive ion binding, approved for Helicobacter pylori infection (Phathom Pharmaceuticals)

See the full article here.

Mannose-methyl-β-cyclodextrin suppresses tumor growth by targeting both colon cancer cells and tumor-associated macrophages

Last week we shared applications of cyclodextrin in various types of cancer, and a discussion was triggered byTamas Sohajda about “why is it always HPBCD that is studied.” In this paper from Kumamoto University, JAPAN, by Keiichi Motoyama, Mannose-methyl-β-cyclodextrin is applied to suppress tumor growth by targeting colon cancer cells and tumor-associated macrophages.

See the full article here.

Evidence of redox imbalance and mitochondrial dysfunction in Niemann-Pick type C 1 patients: the in vitro effect of combined therapy with antioxidants and β‐cyclodextrin nanoparticles

This research contributes to a better understanding of the mechanism of action of #cyclodextrin in Niemann Pick C, which could lead to further applications. Carmen Vargas – Federal University of Rio Grande do Sul evaluated naked and nanoparticle CDs for restoring mitochondrial functions, as well as the beneficial combined effects of treatment with antioxidant N-Acetylcysteine and Coenzyme Q10
Tatiane HammerschmidtBruna DonidaJéssica Lamberty FaverzaniFernanda PolettoDinara Jaqueline Moura

See the full article here

Comparison of the Efficacy and Safety of Adamgammadex with Sugammadex for Reversal of Rocuronium-Induced Neuromuscular Block: Results of a Phase II Clinical Trial

The success of Sugammadex inspired several further cyclodextrin research, including the development of other antidotes and discovering “follow-up” compounds for the same indication. The most advanced candidate in this field is Adamgammadex (developed by Adamerck) with its efficacy recently compared to SGM in a Phase II trial lead by Sichuan University. Although it was used in 2-3 times higher concentrations, the previously reported adverse effects were not observed in this study, including anaphylaxis, haemorrhage, recurarization, abnormal basic vital signs, or lengthened QRS intervals and QT intervals. Adamgammadex was found to be effective for reversing rocuronium-induced neuromuscular block as sugammadex.

See the full article here

Sugar-decorated carbon dots: a novel tool for targeting immunomodulatory receptor

Griffith University (Oren CooperDechao ChenThomas HaselhorstJoseph Tiralongo et al) and University of Bremen released common findings on creating multivalent siglec probes through the decoration of α(2,6)-sialyllactose ligands on inherently fluorescent carbon dots capable of generating a significant cytotoxic effect on Burkitt’s Lymphoma (BL) Daudi B cells.

See the full article here

Turbine Raises €20 Million in Series A Financing to Advance Programs & Partnerships Towards the Clinic with World’s First Cancer Cell Simulation Platform

Turbine Raises €20 Mn to Advance Its Cancer Cell Simulation Platform.
Turbine leverages its technology by identifying associated biomarkers and combination strategies and selecting in vitro and in vivo biological models for experimental validation. Turbine partners with biopharmaceutical companies seeking to deploy simulations to understand patients and overcome causes of resistance hindering drug development in the clinic. 

See the full article on BusinessWire

Weekly round-up of other carbohydrate-related articles (2022/47)

I.
Great review from Universidade de Coimbra (Ana Cláudia Paiva-SantosLaura FerreiraFilipa Mascarenhas MeloSofia RabaçaFrancisco Veiga), Mewar University (Dr. Ankita Mathur), Sharda UniversityUniversity at Buffalo (Dr. Prabhanjan Giram), Shivaji UniversityUniversity of Zabol (Abbas Rahdar), Shanghai Jiao Tong University (Faisal Raza 费赛), Faculdade de Ciências Farmacêuticas – Unicamp (ENG: Pharmacy School – University of Campinas) (Priscila Mazzola) on dermatology and cosmetic applications

Read the full article here

II.
Beta-Cyclodextrins as affordable antivirals to treat coronavirus infection

Read the full article here

III.
Honestly, I am not sure how mankind will handle medication related to space travel. That will be a huge challenge that needs to be studied asap. Recently, the interaction behavior of remdesivir with CDs was studied at ISS (pp 53)

See the NASA e-book here

IV.
How cool is it that you can use CDs to stabilize antigens? Super cool 🙂
Polypseudorotaxane hydrogels based on cyclodextrin and polyethylene glycol significantly improved the stability of antibody preparations and showed no serious adverse effects after subcutaneous injection, suggesting the possibility as safe vaccine formulations to stabilize an antigen protein.
Daiichi University of Pharmacy
Kumamoto University, JAPAN
Hiroshi Itou Hidetoshi Arima Keiichi Motoyama

Read the full article here

V.
Enrichment of bread with α-CD resulted in positive effects on postprandial glycaemia and induced satiety. The incorporation of encapsulated hydroxytyrosol offered similar overall acceptability due to the bitter taste-masking effect provided by α-CD and a slightly additional positive effect in postprandial glycaemia and satiety. The development of foods with favorable metabolic effects is of great importance for the prevention of chronic diseases. The study was prospectively registered in clinicaltrials.gov (NCT04725955, date: 27th January 2021).
Harokopio University of Athens – Panagiota BinouAthena StergiouNikolaos Tentolouris, Vaios K.

See the full article here

VI.
Is the humid autumn whether messing up your hair? Keep calm and use CD-formulations (L’Oréal invention – Cho-Cho Khine and Ronak Rughani) for providing lasting curl definition and/or frizz and/or volume control to hair, even in high humidity.

See the full patent here