Sulfoximines as ATR inhibitors: Analogs of VE-821

Hendriks, Christine M. M.; Hartkamp, Jörg; Wiezorek, Stefan; Steinkamp, Anne‐Dorothee; Rossetti, Giulia; Lüscher, Bernhard; Bolm, Carsten

doi:10.1016/j.bmcl.2017.04.026

Cited by 20 publications

(6 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…101−107 In 2017, Bolm and co-workers published a study describing sulfoximine analogues of the sulfone VE-821, a known ATR inhibitor. 108 The activities of these analogues were comparable to that of VE-821. However, the study was hampered by high concentrations (in the micromolar range) used in their assay, since other ATR inhibitors had IC 50 values in the single-digit nanomolar range.…”

Section: Sulfoximines As a Novel Lead Structure Inmentioning

confidence: 99%

See 1 more Smart Citation

Sulfoximines as Rising Stars in Modern Drug Discovery? Current Status and Perspective on an Emerging Functional Group in Medicinal Chemistry

Mäder¹,

Kattner²

2020

J. Med. Chem.

247

101

View full text Add to dashboard Cite

Sulfoximines have been largely disregarded in medicinal chemistry for a long time. However, recently, they have risen to the apparent level of stardom on the drug discovery scene. Considering the outstanding properties of sulfoximines, this versatile functional group has advanced to implementation in several drug discovery programs. Currently, this fashionable functional group can be found in various hit-to-lead and lead optimization studies in early stages and in several compounds currently in clinical trials. Herein, we review recent developments to demonstrate the scope and limitations of this interesting and versatile functional group in medicinal chemistry and drug discovery.

show abstract

Section: Sulfoximines As a Novel Lead Structure Inmentioning

confidence: 99%

“…In 2017, Bolm and co-workers published a study describing sulfoximine analogues of the sulfone VE-821, a known ATR inhibitor . The activities of these analogues were comparable to that of VE-821.…”

Section: Sulfoximines As a Novel Lead Structure In Medicinal Chemistrymentioning

confidence: 99%

Sulfoximines as Rising Stars in Modern Drug Discovery? Current Status and Perspective on an Emerging Functional Group in Medicinal Chemistry

Mäder¹,

Kattner²

2020

J. Med. Chem.

247

101

View full text Add to dashboard Cite

show abstract

“…However, the establishment of sulforaphane analogues by molecular single atom changes in form of oxygen-to-nitrogen substitutions at the central sulfur, are unprecedented in the context of sulforaphane chemistry. This is surprising, considering that a significant number of other structural variations of sulforaphane are known [10][11][12][13], and that such one-atom modifications have recently led to significant improvements in other medically relevant areas [14][15][16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Novel Broccoli Sulforaphane-Based Analogues Inhibit the Progression of Pancreatic Cancer without Side Effects

et al. 2020

Self Cite

View full text Add to dashboard Cite

The naturally occurring isothiocyanate sulforaphane, found in Brassicaceae vegetables, is promising in cancer treatment, e.g., by the normalization of enhanced levels of NF-κB-signaling in tumor stem cells. We chemically synthesized seven sulforaphane analogues by substitution of the sulfinyl group (S(O)) to either sulfimidoyl (S(NR)) or sulfonimidoyl (S (O) (NR)) groups, and characterized them in the cell lines of pancreatic cancer and several other tumor entities, including the NCI-60 cell panel. MTT and colony forming assays, flow cytometry, immunohistochemistry, microRNA arrays, bioinformatics, tumor xenotransplantation, and Kaplan Meier survival curves were performed. Compared to sulforaphane, the analogue SF102 was most efficient in inhibition of viability, colony formation, tumor growth, and the induction of apoptosis, followed by SF134. Side effects were not observed, as concluded from the body weight and liver histology of chick embryos and survival of C. elegans nematodes. Among 6659 differentially regulated microRNAs, miR29b-1-5p, and miR-27b-5p were downregulated by sulforaphane compared to controls, but upregulated by SF102 and SF134 compared to sulforaphane, suggesting differential signaling. Each substance was involved in the regulation of several NF-κB-related target genes. In conclusion, sulforaphane analogues are promising for the development of highly active new drugs in cancer treatment.

show abstract

“…On the other hand, benzothiazines and benzoisothiazoles are also promising frameworks for the structural diversity they offer and their applications in medicinal chemistry . Various benzothiazine-containing compounds exhibit biological activities such as anticancer, antimicrobial, or anti-inflammatory properties . Among them, the oxicam family has already been marketed (Meloxicam, Piroxicam, etc.).…”

Section: Introductionmentioning

confidence: 99%

Divergent Synthesis of 1,2-Benzo[e]thiazine and Benzo[d]thiazole Analogues Containing a S-Trifluoromethyl Sulfoximine Group: Preparation and New Properties of the Adachi Reagent

Barthelemy

Anselmi

et al. 2019

J. Org. Chem.

View full text Add to dashboard Cite

HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

show abstract

Sulfoximines as ATR inhibitors: Analogs of VE-821

Cited by 20 publications

References 35 publications

Sulfoximines as Rising Stars in Modern Drug Discovery? Current Status and Perspective on an Emerging Functional Group in Medicinal Chemistry

Sulfoximines as Rising Stars in Modern Drug Discovery? Current Status and Perspective on an Emerging Functional Group in Medicinal Chemistry

Novel Broccoli Sulforaphane-Based Analogues Inhibit the Progression of Pancreatic Cancer without Side Effects

Divergent Synthesis of 1,2-Benzo[e]thiazine and Benzo[d]thiazole Analogues Containing a S-Trifluoromethyl Sulfoximine Group: Preparation and New Properties of the Adachi Reagent

Contact Info

Product

Resources

About