Tag: 100-200

Fugger, Kasper; Bajrami, Ilirjana; Silva Dos Santos, Mariana; Young, Sarah Jane; Kunzelmann, Simone; Kelly, Geoff; Hewitt, Graeme; Patel, Harshil; Goldstone, Robert; Carell, Thomas; Boulton, Simon J.; MacRae, James; Taylor, Ian A.; West, Stephen C. published an article in 2021, the title of the article was Targeting the nucleotide salvage factor DNPH1 sensitizes BRCA-deficient cells to PARP inhibitors.Product Details of 4433-40-3 And the article contains the following content:

Mutations in the BRCA1 or BRCA2 tumor suppressor genes predispose individuals to breast and ovarian cancer. In the clinic, these cancers are treated with inhibitors that target poly(ADP-ribose) polymerase (PARP). We show that inhibition of DNPH1, a protein that eliminates cytotoxic nucleotide 5-hydroxymethyl-deoxyuridine (hmdU) monophosphate, potentiates the sensitivity of BRCA-deficient cells to PARP inhibitors (PARPi). Synthetic lethality was mediated by the action of SMUG1 glycosylase on genomic hmdU, leading to PARP trapping, replication fork collapse, DNA break formation, and apoptosis. BRCA1-deficient cells that acquired resistance to PARPi were resensitized by treatment with hmdU and DNPH1 inhibition. Because genomic hmdU is a key determinant of PARPi sensitivity, targeting DNPH1 provides a promising strategy for the hypersensitization of BRCA-deficient cancers to PARPi therapy. The experimental process involved the reaction of 5-(Hydroxymethyl)pyrimidine-2,4(1H,3H)-dione(cas: 4433-40-3).Product Details of 4433-40-3

The Article related to dnph1 brca parp inhibitor sensitizer nucleotide sanitizer smug1, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Product Details of 4433-40-3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On December 31, 2021, Fernandez Montes, Ana; Carmona-Bayonas, Alberto; Jimenez-Fonseca, Paula; Vazquez Rivera, Francisca; Martinez Lago, Nieves; Covela Rua, Marta; Cousillas Castineiras, Antia; Gonzalez Villarroel, Paula; De la Camara Gomez, Juan; Mendez, Jose Carlos Mendez; Carriles Fernandez, Carmen; Sanchez Canovas, Manuel; Garcia Garcia, Teresa published an article.Electric Literature of 65-71-4 The title of the article was Prediction of survival in patients with advanced, refractory colorectal cancer in treatment with trifluridine/tipiracil: real-world vs clinical trial data. And the article contained the following:

Trifluridine/tipiracil increases overall survival (OS) in patients with refractory, metastatic colorectal cancer (mCRC). A post hoc exploratory anal. of the RECOURSE randomized clin. trial (RCT) established two categories, a good prognosis corresponding to subjects having a low tumor burden and indolent disease. Other models in refractory mCRC are the FAS-CORRECT and Colon Life nomogram. The main objective was to externally validate the prognostic factors of the RECOURSE and FAS-CORRECT trials, and the Colon Life nomogram in a multicenter, real-world series of mCRC treated in 3rd and successive lines with trifluridine/tipiracil. The secondary aim was to develop an OS predictive model, TAS-RECOSMO. Between 2016 and 2019, 244 patients were recruited. Median OS was 8.15 vs 8.12 mo for the poor (85% of the subjects) and good (15%) prognosis groups from the RESOURCE trial, resp., log-rank p = 0.9. The most common grade 3-4 toxicities were neutropenia (17%), asthenia (6%), and anemia (5%). The AFT lognormal model TAS-RECOSMO included six variables: ECOG-PS, KRAS/NRAS/BRAF mutation status, time between diagnosis of metastasis and beginning of trifluridine/tipiracil, NLR, CEA, and alk. phosphatase. The models bootstrapped bias-corrected c-index was 0.682 (95% CI, 0.636-0.722). The factors from the Colon Life model, FAS-CORRECT, and RECOURSE displayed a c-index of 0.690, 0.630, and 0.507, resp. TAS-RECOSMO, FAS-CORRECT, and the Colon Life nomogram appear to predict OS in patients with refractory mCCR who begin trifluridine/tipiracil treatment in the real world. The prognostic groups of the RECOURCE RCT were unable to capture the situation of real-world subjects treated with trifluridine/tipiracil in this series. The experimental process involved the reaction of 5-Methylpyrimidine-2,4(1H,3H)-dione(cas: 65-71-4).Electric Literature of 65-71-4

The Article related to trifluridine tipiracil colorectal cancer survival human, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Electric Literature of 65-71-4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On April 1, 2020, Varghese, Anna M.; Cardin, Dana B.; Hersch, Jonathan; Benson, Al B.; Hochster, Howard S.; Makris, Lukas; Hamada, Kensuke; Berlin, Jordan D.; Saltz, Leonard B. published an article.Recommanded Product: 5-Methylpyrimidine-2,4(1H,3H)-dione The title of the article was Phase I study of trifluridine/tipiracil plus irinotecan and bevacizumab in advanced gastrointestinal tumors. And the article contained the following:

Purpose: This two-part phase Ib trial determined the maximum tolerated dose (MTD) of the combination of trifluridine/tipiracil (FTD/TPI) and irinotecan in patients with advanced gastrointestinal tumors, and evaluated the safety, pharmacokinetics, and antitumor activity of the FTD/TPI, irinotecan, and bevacizumab triplet combination in previously treated metastatic colorectal cancer (mCRC). Patients and Methods: Dose escalation (3 + 3 design) in advanced gastrointestinal tumors was followed by expansion in mCRC. During dose escalation, patients received FTD/TPI (20-35 mg/m2 twice daily; days 1-5 of a 14-day cycle) and irinotecan (120-180 mg/m2; day 1). During expansion, the MTD of FTD/TPI and irinotecan plus bevacizumab (5 mg/kg; day 1) was administered. Results: Fifty patients (26 across six dose-escalation cohorts and 24 in the expansion phase) were enrolled. Two dose-limiting toxicities (fatigue and neutropenia) were observed in the dose-escalation phase, and MTD was defined as FTD/TPI 25 mg/m2 twice daily plus irinotecan 180 mg/m2. In the expansion phase, 83% (20/24) experienced any-cause grade ≥3 adverse events (AEs) with the triplet combination, most frequently neutropenia (42%), leukopenia (25%), and diarrhea (12%). AEs of any-cause led to dosing interruptions, modifications, and discontinuations in 29%, 17%, and 4% of patients, resp. No treatment-related deaths occurred. Three patients (12%) experienced partial responses and 16 (67%) patients had stable disease lasting >4 mo. The median progression-free survival was 7.9 mo (95% confidence interval, 5.1-13.4 mo). Conclusions: Tolerability and activity observed in this phase I trial support further investigation of the FTD/TPI-irinotecan-bevacizumab combination in previously treated mCRC. The experimental process involved the reaction of 5-Methylpyrimidine-2,4(1H,3H)-dione(cas: 65-71-4).Recommanded Product: 5-Methylpyrimidine-2,4(1H,3H)-dione

The Article related to trifuridne tipiracil anticancer gastrointestinal tumors, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Recommanded Product: 5-Methylpyrimidine-2,4(1H,3H)-dione

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Satake, Hironaga; Kato, Takeshi; Oba, Koji; Kotaka, Masahito; Kagawa, Yoshinori; Yasui, Hisateru; Nakamura, Masato; Watanabe, Takanori; Matsumoto, Toshihiko; Kii, Takayuki; Terazawa, Tetsuji; Makiyama, Akitaka; Takano, Nao; Yokota, Mitsuru; Okita, Yoshihiro; Matoba, Koreatsu; Hasegawa, Hiroko; Tsuji, Akihito; Komatsu, Yoshito; Yoshino, Takayuki; Yamazaki, Kentaro; Mishima, Hideyuki; Oki, Eiji; Nagata, Naoki; Sakamoto, Junichi published an article in 2020, the title of the article was Phase Ib/II Study of Biweekly TAS-102 in Combination with Bevacizumab for Patients with Metastatic Colorectal Cancer Refractory to Standard Therapies (BiTS Study).Related Products of 65-71-4 And the article contains the following content:

A biweekly TAS-102 plus BEV schedule in patients with heavily pretreated mCRC showed equivalent efficacy with less toxicity compared with the current schedule of TAS-102 plus BEV combination. Biweekly TAS-102 plus BEV combination could reduce unnecessary dose reduction of TAS-102, maintain higher doses, and possibly be effective even in cases without chemotherapy-induced neutropenia (CIN). The prespecified subgroup anal. of this study showed an obvious association between CIN within the first two cycles and prognosis of biweekly TAS-102 plus BEV. TAS-102 (trifluridine/tipiracil) plus bevacizumab (BEV) combination therapy has shown promising activity in patients with metastatic colorectal cancer (mCRC). However, the previously reported dose and schedule for the TAS-102 (70 mg/m2/day on days 1-5 and 8-12, every 4 wk) plus BEV (5 mg/kg on day 1, every 2 wk) regimen is complicated by severe hematol. toxicities and difficult administration schedules. Here, we evaluated the efficacy and safety of a more convenient biweekly TAS-102 plus BEV combination. Patients with mCRC who were refractory or intolerant to standard chemotherapies were enrolled. Patients received biweekly TAS-102 (twice daily on days 1-5, every 2 wk) with BEV (5mg/kg on day 1, every 2 wk). The primary endpoint was progression-free survival rate at 16 wk (16-w PFS rate). From Oct. 2017 to Jan. 2018, 46 patients were enrolled. The recommended phase II dose was determined to be TAS-102 (70 mg/m2/day). Of the 44 eligible patients, the 16-w PFS rate was 40.9% (95% confidence interval, 26.3%-56.8%), and the null hypothesis was rejected (p < .0001). Median progression-free survival (PFS) and overall survival were 4.29 mo and 10.86 mo, resp. Disease control rate was 59.1%. Common grade 3 or higher adverse events were hypertension (40.9%), neutropenia (15.9%), and leucopenia (15.9%). Biweekly TAS-102 plus BEV showed promising antitumor activity with safety. The experimental process involved the reaction of 5-Methylpyrimidine-2,4(1H,3H)-dione(cas: 65-71-4).Related Products of 65-71-4

The Article related to bevacizumab human metastatic colorectal cancer therapy, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Related Products of 65-71-4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On March 24, 2016, Chesworth, Richard; Moradei, Oscar Miguel; Shapiro, Gideon; Jin, Lei; Babine, Robert E. published a patent.Synthetic Route of 1187830-46-1 The title of the patent was CARM1 inhibitors for treating Cancer and Metabolic disorders. And the patent contained the following:

Provided herein are compounds that are useful for inhibiting CARM1 activity. Methods of using the compounds for treating CARM1-mediated disorders are also described. The experimental process involved the reaction of 6,7-Dihydro-5H-pyrrolo[3,4-d]pyrimidine hydrochloride(cas: 1187830-46-1).Synthetic Route of 1187830-46-1

The Article related to carm1 inhibitor preparation cancer metabolic disease, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Synthetic Route of 1187830-46-1

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On May 31, 2015, Dubovitskii, S. N.; Komissarova, N. G.; Shitikova, O. V.; Spirikhin, L. V.; Abdullin, M. F.; Yunusov, M. S. published an article.Computed Properties of 626-48-2 The title of the article was Synthesis of Betulin 28-(2-Bromoacetate) Conjugates with Uracil and its Methyl-Substituted Homologs. And the article contained the following:

A series of potentially biol. active betulin derivatives containing various C-28 2-uracilacetoxy substituents were synthesized [e.g., betulin bromoester I + uracil → II (88%)]. The experimental process involved the reaction of 6-Methylpyrimidine-2,4(1H,3H)-dione(cas: 626-48-2).Computed Properties of 626-48-2

The Article related to betulin uracil conjugate methyl homolog preparation, Terpenes and Terpenoids: Triterpenes (C30), Including Limonoids and other aspects.Computed Properties of 626-48-2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Fitriana, Adita Silvia; Royani, Sri published an article in 2022, the title of the article was Molecular docking study of chalcone derivatives as potential inhibitors of sars-cov-2 main protease.Safety of 6-Methylpyrimidine-2,4(1H,3H)-dione And the article contains the following content:

SARS-CoV-2 main protease is a potential target for the development of AntiCOVID-19. Several chalcones have inhibitory activity against 3CLpro SARSCoV and 3CLpro MERS-CoV. This study aims to predict the potential of chalcones in inhibiting 3CLproSARS-CoV-2, which plays a role in the viral replication process. In silico research carried the prediction through mol. docking toward proteins with PDB ID 6LU7 and 6Y2F. Compound K27 has a docking score more neg. than lopinavir. This result indicates that compound K27 is predicted to inhibit the SARS-CoV-2 replication. The experimental process involved the reaction of 6-Methylpyrimidine-2,4(1H,3H)-dione(cas: 626-48-2).Safety of 6-Methylpyrimidine-2,4(1H,3H)-dione

The Article related to chalcone inhibitor protease mol docking sars cov2, Pharmacology: Effects Of Gastrointestinal and Respiratory Drugs and other aspects.Safety of 6-Methylpyrimidine-2,4(1H,3H)-dione

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On December 31, 2017, Kabal’nova, Natalia N.; Grabovskiy, Stanislav A.; Andriayshina, Nadezhda M.; Egorov, Vladislav I.; Valiullin, Lenar R.; Nabatov, Alexey A.; Raginov, Ivan S.; Murinov, Yurii I. published an article.Related Products of 626-48-2 The title of the article was The Impact of 5-Substituted Uracil Derivatives on Immortalized Embryo Lung Cells. And the article contained the following:

Background: Pyrimidine-based drugs stimulate tissue regeneration and immunity, two components that need to be improved in a number of respiratory diseases of different etiol. (e.g. influenza and asthma). In the present study we investigated relationships between the character of substitutions in the uracil structure and the impact of the resp. uracil derivatives on the immortalized lung cells. Methods: The level of cell proliferation, maximum tolerated dose and toxic effect of 5-substituted uracil derivatives (12 compounds) were studied on the immortalized lung epithelial cells and compared with the ones of 6-methyluracil. Results: 5-Carboxyuracil and 1,3-dimethyl-5-carboxyuracil had the lowest cytotoxicity among the studied compounds Their maximal tolerated dosage values were 5 times higher whereas the proliferation index was increased by 25% and 75%, resp., compared to 6-methyluracil, known for its pos. effects on cell regeneration. Conclusion: 5-Carboxyuracil and 1,3-dimethyl-5-carboxyuracil have the best perspectives for further studies on their biol. effects. The experimental process involved the reaction of 6-Methylpyrimidine-2,4(1H,3H)-dione(cas: 626-48-2).Related Products of 626-48-2

The Article related to uracil derivative immortalize embryo lung cell, Pharmacology: Effects Of Gastrointestinal and Respiratory Drugs and other aspects.Related Products of 626-48-2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On January 1, 2018, Aybastier, Onder; Dawbaa, Sam; Demir, Cevdet published an article.Related Products of 4433-40-3 The title of the article was Investigation of antioxidant ability of grape seeds extract to prevent oxidatively induced DNA damage by gas chromatography-tandem mass spectrometry. And the article contained the following:

Phenolic compounds have been studied elaborately for their efficacy to improve health and to protect against a wide variety of diseases. Herein this study, different anal. methods were implemented to evaluate the antioxidant properties of catechin and cyanidin using their standard substances and as they found in the grape seeds extracts Total phenol contents were 107.39 ± 8.94 mg GAE/g dw of grape seeds for grape seed extract (GSE) and 218.32 ± 10.66 mg GAE/g dw of grape seeds for acid-hydrolyzed grape seed extract (AcGSE). The extracts were analyzed by HPLC-DAD system and the results showed the presence of catechin, gallic acid, chlorogenic acid and ellagic acid in the processed methanolic extract and cyanidin, gallic acid and ellagic acid in the processed acidified methanolic extract The protective abilities of catechin and cyanidin were tested against the oxidation of DNA. The results showed that cyanidin has better protection of DNA against oxidation than catechin. GSE and AcGSE were revealed to inhibit the oxidatively induced DNA damage. GSE decreased about 57% of damage caused by the Fenton control sample. This study could show new aspects of the antioxidant profiles of cyanidin and catechin. The experimental process involved the reaction of 5-(Hydroxymethyl)pyrimidine-2,4(1H,3H)-dione(cas: 4433-40-3).Related Products of 4433-40-3

The Article related to dna oxidative damage grape seed extract antioxidant, antioxidant, catechin, cyanidin, dna oxidation, gc–ms/ms, grape seed, Food and Feed Chemistry: Fruits, Vegetables, Legumes, and Nuts and other aspects.Related Products of 4433-40-3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On October 26, 2016, Shen, Weifeng; Han, Wei; Li, Yunong; Meng, Zhiqi; Cai, Leiming; Li, Liang published an article.Computed Properties of 4433-40-3 The title of the article was Development of chemical isotope labeling liquid chromatography mass spectrometry for silkworm hemolymph metabolomics. And the article contained the following:

Silkworm (Bombyx mori) is a very useful target insect for evaluation of endocrine disruptor chems. (EDCs) due to mature breeding techniques, complete endocrine system and broad basic knowledge on developmental biol. Comparative metabolomics of silkworms with and without EDC exposure offers another dimension of studying EDCs. The authors report a workflow on metabolomic profiling of silkworm hemolymph based on high-performance chem. isotope labeling (CIL) liquid chromatog. mass spectrometry (LC-MS) and demonstrate its application in studying the metabolic changes associated with the pesticide dichlorodiphenyltrichloroethane (DDT) exposure in silkworm. Hemolymph samples were taken from mature silkworms after growing on diet that contained DDT at four different concentrations (1, 0.1, 0.01, 0.001 ppm) as well as on diet without DDT as controls. They were subjected to differential 12C-/13C-dansyl labeling of the amine/phenol submetabolome, LC-UV quantification of the total amount of labeled metabolites for sample normalization, and LC-MS detection and relative quantification of individual metabolites in comparative samples. The total concentration of labeled metabolites did not show any significant change between four DDT-treatment groups and one control group. Multivariate statistical anal. of the metabolome data set showed that there was a distinct metabolomic separation between the five groups. Out of the 2044 detected peak pairs, 338 and 1471 metabolites have been putatively identified against the HMDB database and the EML library, resp. 65 metabolites were identified by the dansyl library searching based on the accurate mass and retention time. Among the 65 identified metabolites, 33 pos. metabolites had changes of >1.20-fold or <0.83-fold in one or more groups with p-value of smaller than 0.05. Several useful biomarkers including serine, methionine, tryptophan, asym. dimethylarginine, N-Methyl-D-aspartic and tyrosine were identified. The changes of these biomarkers were likely due to the disruption of the endocrine system of silkworm by DDT. This work illustrates that the method of CIL LC-MS is useful to generate quant. submetabolome profiles from a small volume of silkworm hemolymph with much higher coverage than conventional LC-MS methods, thereby facilitating the discovery of potential metabolite biomarkers related to EDC or other chem. exposure. The experimental process involved the reaction of 5-(Hydroxymethyl)pyrimidine-2,4(1H,3H)-dione(cas: 4433-40-3).Computed Properties of 4433-40-3

The Article related to isotope labeling hplc mass spectrometry silkworm hemolymph metabolomics, isotope labeling, liquid chromatography, mass spectrometry, metabolomics, pesticide, silkworm, Biochemical Methods: Other (Not Covered At Other Subsections) and other aspects.Computed Properties of 4433-40-3

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia