Day: November 3, 2022

On February 24, 2010, Xu, Kefu published a patent.Name: 5-(3,4,5-Trimethoxybenzyl)pyrimidine-2,4-diamine 2-hydroxypropanoate The title of the patent was Medical composition for treating chicken necrotizing enterocolitis and its preparation. And the patent contained the following:

The title medical composition contains apramycin sulfate 2-10, sulfamethoxydiazine sodium 2-15, trimethoprim lactate 0.4-3, atropine sulfate 0.1-0.5%, and tannic acid. The preparation method comprises pulverizing and screening raw materials, weighing, and sufficiently mixing for 1h to obtain. This inventive composition can be used for treating chicken necrotizing enterocolitis. The experimental process involved the reaction of 5-(3,4,5-Trimethoxybenzyl)pyrimidine-2,4-diamine 2-hydroxypropanoate(cas: 23256-42-0).Name: 5-(3,4,5-Trimethoxybenzyl)pyrimidine-2,4-diamine 2-hydroxypropanoate

The Article related to chicken necrotizing enterocolitis apramycin sulfamethoxydiazine trimethoprim lactate atropine tannate, trimethoprim lactate atropine sulfate tannic acid, Pharmacology: Effects Of Gastrointestinal and Respiratory Drugs and other aspects.Name: 5-(3,4,5-Trimethoxybenzyl)pyrimidine-2,4-diamine 2-hydroxypropanoate

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

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 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

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

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 August 5, 2021, Heymach, John; Robichaux, Jacqulyne published a patent.Safety of 4-Chloro-6-fluoropyrido[3,4-d]pyrimidine The title of the patent was Use of quinazoline-based tyrosine kinase inhibitors for the treatment of cancers with NRG1 fusions. And the patent contained the following:

Provided herein are methods of selecting cancer patients for treatment with quinazoline-based tyrosine kinase inhibitors, either alone or in combination with anti-HER2/HER3 antibodies, as well as methods of treating cancer patients so selected. Cancer patients are selected for treatment if their cancer has an NRG1 fusion. Selected patients are then treated with quinazoline-based tyrosine kinase inhibitors alone or in combination with anti-HER2/HER3 antibodies. The experimental process involved the reaction of 4-Chloro-6-fluoropyrido[3,4-d]pyrimidine(cas: 175357-98-9).Safety of 4-Chloro-6-fluoropyrido[3,4-d]pyrimidine

The Article related to tyrosine kinase inhibitor quinazoline her antibody nrg1 fusion cancer, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Safety of 4-Chloro-6-fluoropyrido[3,4-d]pyrimidine

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On March 31, 2020, Pfeiffer, Per; Yilmaz, Mette; Moller, Soren; Zitnjak, Daniela; Krogh, Merete; Petersen, Lone Noergaard; Poulsen, Laurids Oestergaard; Winther, Stine Braendegaard; Thomsen, Karina Gravgaard; Qvortrup, Camilla published an article.Recommanded Product: 65-71-4 The title of the article was TAS-102 with or without bevacizumab in patients with chemorefractory metastatic colorectal cancer: an investigator-initiated, open-label, randomised, phase 2 trial. And the article contained the following:

TAS-102 (trifluridine-tipiracil) has shown a significant overall survival benefit compared with placebo in patients with chemorefractory metastatic colorectal cancer. Inspired by the encouraging results of a small phase 1-2 study, C-TASK FORCE, which evaluated the combination of TAS-102 plus bevacizumab in patients with chemorefractory metastatic colorectal cancer, we aimed to compare the efficacy of TAS-102 plus bevacizumab vs. TAS-102 monotherapy in patients receiving refractory therapy for metastatic colorectal cancer . This investigator-initiated, open-label, randomized, phase 2 study enrolled patients (aged ≥18 years) with metastatic colorectal from four cancer centers in Denmark. The main inclusion criteria were histopathol. confirmed metastatic colorectal cancer refractory or intolerant to a fluoropyrimidine, irinotecan, oxaliplatin, and cetuximab or panitumumab (only for RAS wild-type), and WHO performance status of 0 or 1. Previous therapy with bevacizumab, aflibercept, ramucirumab, or regorafenib was allowed but not mandatory. Participants were enrolled and randomly assigned (1:1) in block sizes of two, four, or six by a web-based tool to receive oral TAS-102 (35 mg/m2 twice daily on days 1-5 and 8-12 every 28 days) alone or combined with i.v. bevacizumab (5 mg/kg on days 1 and 15) until progression, unacceptable toxicity, or patient decision to withdraw. Treatment assignment was not masked, and randomization was stratified by institution and RAS mutation status. The primary endpoint was investigator-evaluated progression-free survival. All analyses were based on intention to treat. This trial is registered with EudraCT, 2016-005241-23. From Aug 24, 2017, to Oct 31, 2018, 93 patients were enrolled and randomly assigned to TAS-102 (n = 47) or TAS-102 plus bevacizumab (n = 46). The clin. cut-off date was Feb 15, 2019, after a median follow-up of 10.0 mo (IQR 6.8-14.0). Median progression-free survival was 2.6 mo (95% CI 1.6-3.5) in the TAS-102 group vs. 4.6 mo (3.5-6.5) in the TAS-102 plus bevacizumab group (hazard ratio 0.45 [95% CI 0.29-0.72]; p = 0.0015). The most frequent grade 3 or worse adverse event was neutropenia (18 [38%] of 47 in the TAS-102 monotherapy group vs 31 [67%] of 46 in the TAS-102 plus bevacizumab group). Serious adverse events were observed in 21 (45%) patients in the TAS-102 group and 19 (41%) in the TAS-102 plus bevacizumab group. No deaths were deemed treatment related. In patients with chemorefractory metastatic colorectal cancer, TAS-102 plus bevacizumab, as compared with TAS-102 monotherapy, was associated with a significant and clin. relevant improvement in progression-free survival with tolerable toxicity. The combination of TAS-102 plus bevacizumab could be a new treatment option for patients with refractory metastatic colorectal cancer and could be a practice-changing development.Servier. The experimental process involved the reaction of 5-Methylpyrimidine-2,4(1H,3H)-dione(cas: 65-71-4).Recommanded Product: 65-71-4

The Article related to tas bevacizumab fluoropyrimidine anticancer agent colorectal cancer metastasis, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Recommanded Product: 65-71-4

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Ogata, Misato; Kotaka, Masahito; Ogata, Takatsugu; Hatachi, Yukimasa; Yasui, Hisateru; Kato, Takeshi; Tsuji, Akihito; Satake, Hironaga published an article in 2020, the title of the article was Regorafenib vs trifluridine/tipiracil for metastatic colorectal cancer refractory to standard chemotherapies: A multicenter retrospective comparison study in Japan.COA of Formula: C5H6N2O2 And the article contains the following content:

Regorafenib (REG) and trifluridine/tipiracil (FTD/TPI) showed survival benefits in metastatic colorectal cancer patients previously treated with standard chemotherapies; therefore, we compared the efficacy and safety of these two treatments. Patients with metastatic colorectal cancer treated with REG or FTD/TPI as a salvage-line therapy from May 2014 to Dec. 2017 were included. We retrospectively analyzed long-term survival, safety, and clin. outcomes. Among 134 patients, 57 and 77 received REG and FTD/TPI, resp. The REG group received more prior systemic chemotherapies and significantly more frequent addnl. chemotherapies than the FTD/TPI group did. The median follow-up was 6.2 mo, whereas the median overall survival was 9.9 and 11.4 mo in the REG and FTD/TPI groups, resp. (hazard ratio = 0.954, p = 0.837). The median progression-free survival was 2.0 and 3.3 mo in the REG and FTD/TPI groups, resp. (hazard ratio = 0.52, p = 0.00047), indicating significant differences, whereas the objective response and disease control rates did not differ. The median overall survival of patients with addnl. subsequent chemotherapies after disease progression was longer than that of patients without addnl. chemotherapy. The most frequent grade ≥3 adverse events were hypertension and neutropenia in the REG and FTD/TPI groups, resp. Our study suggested that sequential use of both drugs may prolong survival. The experimental process involved the reaction of 5-Methylpyrimidine-2,4(1H,3H)-dione(cas: 65-71-4).COA of Formula: C5H6N2O2

The Article related to metastatic colorectal cancer regorafenib trifluridine tipiracil chemotherapy japan, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.COA of Formula: C5H6N2O2

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

On January 31, 2021, Yoshida, Yoichiro; Yamada, Takeshi; Kamiyama, Hirohiko; Kosugi, Chihiro; Ishibashi, Keiichiro; Yoshida, Hiroshi; Ishida, Hideyuki; Yamaguchi, Satoru; Kuramochi, Hidekazu; Fukazawa, Atsuko; Sonoda, Hiromichi; Yoshimatsu, Kazuhiko; Matsuda, Akihisa; Hasegawa, Suguru; Sakamoto, Kazuhiro; Otsuka, Toshiaki; Koda, Keiji; TAS CC3 Study Group. published an article.Reference of 5-Methylpyrimidine-2,4(1H,3H)-dione The title of the article was Combination of TAS-102 and bevacizumab as third-line treatment for metastatic colorectal cancer: TAS-CC3 study. And the article contained the following:

Abstract: Our study exclusively examined patients receiving this combination as a third-line treatment to investigate the clin. impact beyond cytotoxic doublets. Methods: This investigator-initiated, open-label, single-arm, multi-centered phase II study was conducted in Japan. Eligible CRC patients were refractory or intolerant to fluoropyrimidine, irinotecan, and oxaliplatin in first- and second-line therapy. TAS-102 (35 mg/m2) was given orally twice daily on days 1-5 and 8-12 in a 4-wk cycle, and bevacizumab (5 mg/kg) was administered by i.v. infusion every 2 wk. The primary endpoint was PFS and the secondary endpoints were time-to-treatment failure, response rate, overall survival (OS), and safety. Results: Between June 2016 and August 2017, 32 patients were enrolled. All patients previously received bevacizumab. The median PFS was 4.5 mo; the median overall survival was 9.3 mo. Partial response was observed in two patients. The most common adverse events above grade 3 were neutropenia followed by thrombocytopenia. There were no non-hematol. adverse events above grade 3 and no treatment-related deaths occurred. Conclusions: This study met its primary endpoint of PFS, which is comparable to the results of the C-TASK FORCE study. The TAS-102 and bevacizumab combination has the potential to be a therapeutic option for third-line treatment of metastatic CRC. The experimental process involved the reaction of 5-Methylpyrimidine-2,4(1H,3H)-dione(cas: 65-71-4).Reference of 5-Methylpyrimidine-2,4(1H,3H)-dione

The Article related to metastatic colorectal cancer tas 102 bevacizumab japan, bevacizumab, chemotherapy, colorectal cancer, neutropenia, tas-102, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Reference of 5-Methylpyrimidine-2,4(1H,3H)-dione

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia