Day: October 12, 2022

Zhang, Xiaoyu; Luukkonen, Lena M.; Eissler, Christie L.; Crowley, Vincent M.; Yamashita, Yu; Schafroth, Michael A.; Kikuchi, Shota; Weinstein, David S.; Symons, Kent T.; Nordin, Brian E.; Rodriguez, Joe L.; Wucherpfennig, Thomas G.; Bauer, Ludwig G.; Dix, Melissa M.; Stamos, Dean; Kinsella, Todd M.; Simon, Gabriel M.; Baltgalvis, Kristen A.; Cravatt, Benjamin F. published the artcile< DCAF11 Supports Targeted Protein Degradation by Electrophilic Proteolysis-Targeting Chimeras>, HPLC of Formula: 1003-32-3, the main research area is DCAF11 targeted protein degradation electrophilic PROTAC cancer.

Ligand-induced protein degradation has emerged as a compelling approach to promote the targeted elimination of proteins from cells by directing these proteins to the ubiquitin-proteasome machinery. So far, only a limited number of E3 ligases have been found to support ligand-induced protein degradation, reflecting a dearth of E3-binding compounds for proteolysis-targeting chimera (PROTAC) design. Here, we describe a functional screening strategy performed with a focused library of candidate electrophilic PROTACs to discover bifunctional compounds that degrade proteins in human cells by covalently engaging E3 ligases. Mechanistic studies revealed that the electrophilic PROTACs act through modifying specific cysteines in DCAF11, a poorly characterized E3 ligase substrate adaptor. We further show that DCAF11-directed electrophilic PROTACs can degrade multiple endogenous proteins, including FBKP12 and the androgen receptor, in human prostate cancer cells. Our findings designate DCAF11 as an E3 ligase capable of supporting ligand-induced protein degradation via electrophilic PROTACs.

Journal of the American Chemical Society published new progress about Androgen receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, HPLC of Formula: 1003-32-3.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Bumbu, Valentina D.; Yang, Xing; Birman, Vladimir B. published the artcile< Kinetic Resolution of N-Acyl-Thiolactams via Catalytic Enantioselective Deacylation>, Application of C10H11NS2, the main research area is kinetic resolution acyl thiolactam catalytic enantioselective deacylation benzotetramisole.

Methanolysis of N-acylthiazolidin-2-thiones and -oxazolidin-2-thiones in the presence of acyl transfer catalyst benzotetramisole (BTM) proceeds in a highly enantioselective fashion thus enabling kinetic resolution of these substrates [e.g., treatment of thiolactam (±)-I with MeOH, catalyst II and PhCO2H afforded (S)-III + (R)-I with s = 84].

Organic Letters published new progress about Acylation catalysts (stereoselective). 171877-39-7 belongs to class thiazole, and the molecular formula is C10H11NS2, Application of C10H11NS2.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Nizamuddin, N. D.; Abdul Ahad, Hindustan; Devanna, Nayakanti published the artcile< Synthesis and molecular docking studies of some 1,2-dimethyl-3(4-substituted phenyl-1,3-thiazol-2-yl)2,3-dihydroquinazolin-4(1H)-ones as anticancer agents>, Synthetic Route of 57493-24-0, the main research area is dimethyl phenyl thiazolyl dihydroquinazolinone preparation mol docking.

Synthesis of 1, 2-dimethyl-3(4-substituted phenyl-1,3-thiazol-2-yl)2,3-dihydro quinazolin-4(1H)-ones derivatives I [R = 4-Me, 2-OH, 4-Cl, etc.] was effected by refluxing 1,2-dimethylbenzoxazine-4-one with different 4-substituted phenyl-1,3-thiazol-2-amines. Synthesized compoundsI were characterized through elemental anal., IR, proton NMR, and Carbon-13 NMR. Mol. docking studies were carried out using Schrodinger Glide (version 2020_1) which was docked into selective P38alpha and Activin A Receptor Type 1 (ACVR1) Activin receptor-like kinase-2 (ALK2) kinase with Protein Data Bank (PDB) code 3GC7, 6GI6. Based on the docking score of synthesized quinazolin-4-one derivatives, I co-crystallized ligands interaction was evaluated with 5-fluorouracil (5-FU) as a reference drug. Compounds I [R = H, 4-MeO, 3-NH2, 2,4-OH] with P38alpha, I [R = 2-OH, 3-NH2, 4-Cl, 2,4-OH] with ACVR1 (ALK2) kinase score were -7.265, -7.078, -7.058 and -6.836; -8.929, -8.749, -8.735 and -8.464 Kcal/mol against enzymes responsible for cancer treatment. The results indicated that quinazolin-4-one derivatives I scored better than ligand and 5-FU.

Indian Journal of Heterocyclic Chemistry published new progress about Acetophenones Role: RCT (Reactant), RACT (Reactant or Reagent). 57493-24-0 belongs to class thiazole, and the molecular formula is C9H7N3O2S, Synthetic Route of 57493-24-0.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Lakhan, Ram; Singh, Om Prakash published the artcile< Local anesthetics. Part-III: synthesis of 2-(N-substituted or N,N-disubstituted aminoacetamido)-4 arylthiazoles>, COA of Formula: C9H7N3O2S, the main research area is aminoacetamidothiazole aryl local anesthetic preparation; phenylthiazole aminoacetamido local anesthetic preparation.

Title compounds I [R = 4-O2NC6H4, 3-O2NC6H4, 2,5-(MeO)2C6H3; R1 = Et, Me2CH, Me2CHCH2, MeEtCH; R2 = H, Et; R1R2 = piperidino] were prepared E.g., cyclocondensation of 4-O2NC6H4COMe with thiourea gave thiazole II, chloroacetylation of which followed by amination with EtNH2 gave I (R = 4-O2NC6H4, R1 = Et, R2 = H). I HCl (R = 3-O2NC6H4, R1 = MeEtCH, R2 = H) showed local anesthetic activity superior to that of procaine HCl.

Journal of the Indian Chemical Society published new progress about Local anesthetics. 57493-24-0 belongs to class thiazole, and the molecular formula is C9H7N3O2S, COA of Formula: C9H7N3O2S.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Jiang, Xingyu; Hartwig, John F. published the artcile< Iridium-Catalyzed Enantioselective Allylic Substitution of Aliphatic Esters with Silyl Ketene Acetals as the Ester Enolates>, Related Products of 1003-32-3, the main research area is homoallylic ester regioselective diastereoselective enantioselective preparation; ester aliphatic silyl ketene acetal regioselective enantioselective allylic substitution; alkylation; asymmetric catalysis; enantioselectivity; esters; iridium.

An iridium-catalyzed enantioselective allylic substitution of aliphatic esters (E)-R1CH:CHCH2OC(O)Ph (R1 = Ph, 4-MeC6H4, 2-thienyl, 3-pyridyl, etc.) with silyl ketene acetals R22C:C(OR3)SiMe3 [R2 = Me, Et; R22 = (CH2)3, (CH2)5, (CH2)2O(CH2)2, etc.; R3 = Me, i-Pr, t-Bu, Ph, etc.] to form products containing a quaternary carbon atom at the nucleophile moiety and a tertiary carbon atom at the electrophile moiety is reported. Under relatively neutral conditions, the allylated aliphatic esters H2C:CHCH(R1)CR22CO2R3 were obtained with excellent regio- and enantioselectivity. These products were readily converted into primary alcs., carboxylic acids, amides, isocyanates, and carbamates, as well as THF and γ-butyrolactone derivatives, without erosion of enantiomeric purity.

Angewandte Chemie, International Edition published new progress about Acetals, ketene, silyl Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Related Products of 1003-32-3.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Lu, Zheng; Yang, Yong-Qing; Xiong, Weixiang published the artcile< Preparation of 1,3-Thiazolidine-2-thiones by Using Potassium Ethylxanthate as a Carbon Disulfide Surrogate>, HPLC of Formula: 96-53-7, the main research area is thiazolidine thione preparation green chem; amino alc potassium ethylxanthate heterocyclization.

A simple procedure is presented for preparing 1,3-thiazolidine-2-thiones, e.g., I by using potassium ethylxanthate and the corresponding β-amino alcs. as the starting materials in the presence of ethanol.

Synlett published new progress about Amino alcohols Role: RCT (Reactant), RACT (Reactant or Reagent). 96-53-7 belongs to class thiazole, and the molecular formula is C3H5NS2, HPLC of Formula: 96-53-7.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Chen, Yufeng; He, Rong; Chen, Yihua; D’Annibale, Melissa A.; Langley, Brett; Kozikowski, Alan P. published the artcile< Studies of Benzamide- and Thiol-Based Histone Deacetylase Inhibitors in Models of Oxidative-Stress-Induced Neuronal Death: Identification of Some HDAC3-Selective Inhibitors>, Product Details of C9H7N3O2S, the main research area is histone deacetylase inhibitor preparation neuroprotective structure activity.

Less stress: We compare three structurally different classes of histone deacetylase (HDAC) inhibitors that contain benzamide, hydroxamate, or thiol groups as the zinc binding group (ZBG) for their ability to protect cortical neurons in culture from cell death induced by oxidative stress. Novel benzamide-based ligands selectively inhibit HDAC3 but provide no neuroprotection in the HCA-cortical neuron model of oxidative stress. We compare three structurally different classes of histone deacetylase (HDAC) inhibitors that contain benzamide, hydroxamate, or thiol groups as the zinc binding group (ZBG) for their ability to protect cortical neurons in culture from cell death induced by oxidative stress. This study reveals that none of the benzamide-based HDAC inhibitors (HDACIs) provides any neuroprotection whatsoever, in distinct contrast to HDACIs that contain other ZBGs. Some of the sulfur-containing HDACIs, namely the thiols, thioesters, and disulfides present modest neuroprotective activity but show toxicity at higher concentrations Taken together, these data demonstrate that the HDAC6-selective mercaptoacetamides that were reported previously provide the best protection in the homocysteic acid model of oxidative stress, thus further supporting their study in animal models of neurodegenerative diseases.

ChemMedChem published new progress about Cell death. 57493-24-0 belongs to class thiazole, and the molecular formula is C9H7N3O2S, Product Details of C9H7N3O2S.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Krasitskaya, Vasilisa V.; Bashmakova, Eugenia E.; Frank, Ludmila A. published the artcile< Coelenterazine-dependent luciferases as a powerful analytical tool for research and biomedical applications>, Synthetic Route of 2591-17-5, the main research area is review coelenterazine luciferase bioluminescent system; Ca2+-regulated photoprotein; analytical systems; bioluminescence; coelenterazine; luciferase.

A review. The functioning of bioluminescent systems in most of the known marine organisms is based on the oxidation reaction of the same substrate-coelenterazine (CTZ), catalyzed by luciferase. Despite the diversity in structures and the functioning mechanisms, these enzymes can be united into a common group called CTZ-dependent luciferases. Among these, there are two sharply different types of the system organization-Ca2+-regulated photoproteins and luciferases themselves that function in accordance with the classical enzyme-substrate kinetics. Along with deep and comprehensive fundamental research on these systems, approaches and methods of their practical use as highly sensitive reporters in analytics have been developed. The research aiming at the creation of artificial luciferases and synthetic CTZ analogs with new unique properties has led to the development of new exptl. anal. methods based on them. The com. availability of many ready-to-use assay systems based on CTZ-dependent luciferases is also important when choosing them by first-time-users. The development of anal. methods based on these bioluminescent systems is currently booming. The bioluminescent systems under consideration were successfully applied in various biol. research areas, which confirms them to be a powerful anal. tool. In this , we consider the main directions, results, and achievements in research involving these luciferases.

International Journal of Molecular Sciences published new progress about 2591-17-5. 2591-17-5 belongs to class thiazole, and the molecular formula is C11H8N2O3S2, Synthetic Route of 2591-17-5.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Diaz, Rodrigo D.; Larrondo, Luis F. published the artcile< A circadian clock in Neurospora crassa functions during plant cell wall deconstruction>, Name: (S)-2-(6-Hydroxybenzo[d]thiazol-2-yl)-4,5-dihydrothiazole-4-carboxylic acid, the main research area is Neurospora cell wall circadian clock; Cellulose degradation; Clock Regulation; Luciferase real-time reporter.

Circadian clocks are autonomous timers that are believed to confer organisms a selective advantage by enabling processes to occur at appropriate times of the day. In the model fungus Neurospora crassa, 20-40% of its genes are reported to be under circadian regulation, as assayed in simple sugar media. Although it has been well-described that Neurospora efficiently deconstructs plant cell wall components, little is known regarding the status of the clock when Neurospora grows on cellulosic material, or whether such a clock has an impact on any of the genes involved in this process. Through luciferase-based reporters and fluorescent detection assays, we show that a clock is functioning when Neurospora grows on cellulose-containing wheat straw as the only carbon and nitrogen source. Addnl., we found that the major cellobiohydrolase encoding gene involved in plant cell wall deconstruction, cbh-1, is rhythmically regulated by the Neurospora clock, in a manner that depends on cellulose concentration and on the transcription factor CRE-1, known as a key player in carbon-catabolite repression in this fungus. Our findings are a step towards a more comprehensive understanding on how clock regulation modulates cellulose degradation, and thus Neurospora’s physiol.

Fungal Biology published new progress about Cell wall. 2591-17-5 belongs to class thiazole, and the molecular formula is C11H8N2O3S2, Name: (S)-2-(6-Hydroxybenzo[d]thiazol-2-yl)-4,5-dihydrothiazole-4-carboxylic acid.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Loretz, Carol; Ho, Ming-Chih David; Alam, Novera; Mitchell, Walter; Li, Albert P. published the artcile< Application of cryopreserved human intestinal mucosa and cryopreserved human enterocytes in the evaluation of herb-drug interactions: evaluation of CYP3A inhibitory potential of grapefruit juice and commercial formulations of twenty-nine herbal supplements>, Category: thiazole, the main research area is Application cryopreserved human intestinal mucosa drug interaction.

Com. formulations of 29 commonly used herbal supplements (HSs) and grapefruit juice were evaluated for drug interaction potential via quantification of their CYP3A inhibitory potential in two in vitro exptl. models of human small intestine, cryopreserved human intestinal mucosa (CHIM), and cryopreserved human enterocytes (CHEs). Two CYP3A substrates were used-in the studies with CHIM, CYP3A activity was quantified via liquid chromatog. tandem mass spectrometry quantification of midazolam 1′-hydroxylation, whereas in CHE, luciferin-IPA metabolism to luciferin was quantified by luminescence. Upon treatment of CHIM with the estimated lumen concentration of the HS upon each oral administration (manufacturers’ recommended dosage dissolved in 200 mL of culture medium), >80% CYP3A inhibition was observed for green tea extract, St. John’s wort, valerian root, horehound, and grapefruit juice. Less than 50% inhibition was observed for fenugreek, aloe vera, guarana, soy isoflavone, maca, echinacea, spirulina, evening primrose, milk thistle, cranberry, red yeast rice, rhodiola, ginkgo biloba, turmeric, curcumin, white kidney bean, garlic, cinnamon, saw palmetto berries, panax ginseng, black elderberry, wheat grass juice, flaxseed oil, black cohosh, and ginger root. The results were confirmed in a a dose-response study with HSs obtained from three suppliers for the four inhibitory HSs (green tea extract, horehound, St). John’s wort, valerian root and three representative noninhibitory HSs (black cohosh, black elderberry, echinacea). Similar results were obtained with the inhibitory HSs in CHE. The results illustrate that CHIM and CHE represent physiol. relevant in vitro exptl. models for the evaluation of drug interaction potential of herbal supplements. Based on the results, green tea extract, horehound, St. John’s wort, and valerian root may cause drug interactions with orally administered drugs that are CYP3A substrates, as was observed for grapefruit juice.

Drug Metabolism & Disposition published new progress about Allium sativum. 2591-17-5 belongs to class thiazole, and the molecular formula is C11H8N2O3S2, Category: thiazole.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica