Schoning, Verena et al. published their research in Toxicology Letters in 2018 | CAS: 850879-09-3

N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3) belongs to benzofurans derivatives.Benzofuran is one of the most significant oxygen-containing heterocycles consisting of fused benzene and furan ring, which are widely presented in various naturally occurring and synthetically active compounds. Substituted benzofurans find applications such as fluorescent sensors, oxidants, in drug discovery, and in another field of chemistry and agriculture.SDS of cas: 850879-09-3

The hepatotoxic potential of protein kinase inhibitors predicted with Random Forest and Artificial Neural Networks was written by Schoning, Verena;Krahenbuhl, Stephan;Drewe, Jurgen. And the article was included in Toxicology Letters in 2018.SDS of cas: 850879-09-3 This article mentions the following:

Protein kinases (PKs) play a role in many pivotal aspects of cellular function. Dysregulation and mutations of protein kinases are involved in the development of different diseases, which might be treated by inhibition of the corresponding kinase. Protein kinase inhibitors (PKIs) are generally well tolerated, but unexpected and serious adverse events on the heart, lung, kidney and liver were observed clin. In this study, the structure-activity relationship of PKIs in relation to hepatotoxicity was investigated. A dataset of 165 PKIs was compiled and the probability of human hepatotoxicity with two different machine learning algorithms (Random Forest and Artificial Neural Networks) was analyzed. The estimated probability of hepatotoxicity was generally high for single PKIs. However, depending on the target kinase of the PKI, a difference in hepatotoxic potential could be observed The similarity of the PKIs to each other is caused by the conserved site of action of the protein kinases. Hepatotoxicity may therefore always be an issue in PKIs. In the experiment, the researchers used many compounds, for example, N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3SDS of cas: 850879-09-3).

N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3) belongs to benzofurans derivatives.Benzofuran is one of the most significant oxygen-containing heterocycles consisting of fused benzene and furan ring, which are widely presented in various naturally occurring and synthetically active compounds. Substituted benzofurans find applications such as fluorescent sensors, oxidants, in drug discovery, and in another field of chemistry and agriculture.SDS of cas: 850879-09-3

Referemce:
Benzofuran – Wikipedia,
Benzofuran | C8H6O – PubChem

Mahadevan, Daruka et al. published their research in Oncotarget in 2015 | CAS: 850879-09-3

N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3) belongs to benzofurans derivatives. Benzofurans are only weakly aromatic in nature and they are cleaved by many oxidative and reductive conditions. Introduction of benzofurans in organic synthesis, particularly drug synthesis, involves generally the use of their metalated species as nucleophiles in addition reactions or in metal-catalysed cross-coupling reactions.COA of Formula: C23H21N5O3S

Novel receptor tyrosine kinase targeted combination therapies for imatinib-resistant gastrointestinal stromal tumors (GIST). was written by Mahadevan, Daruka;Theiss, Noah;Morales, Carla;Stejskal, Amy E;Cooke, Laurence S;Zhu, Min;Kurtzman, Drew;Swart, Rachel;Ong, Evan;Qi, Wenqing. And the article was included in Oncotarget in 2015.COA of Formula: C23H21N5O3S This article mentions the following:

BACKGROUND: c-Kit/α-PDGFR targeted therapies are effective for gastrointestinal stromal tumors (GIST), but, >50% develop drug resistance. METHODS: RTK expression (c-Kit, c-Met, AXL, HER-1, HER-2, IGF-1R) in pre-/post-imatinib (IM) GIST patient samples (n=16) and 4 GIST cell lines were examined for RTK inhibitor activity. GIST-882 cells were cultured in IM every other day, cells collected (1 week to 6 months) and analyzed by qRT-PCR and Western blotting. RESULTS: Immunohistochemistry pre-/post-IM demonstrated continued expression of c-Kit and HER1, while a subset expressed IGF-1R, c-Met and AXL. In GIST cells (GIST-882, GIST430/654, GIST48) c-Kit, HER1 and c-Met are co-expressed. Acute IM over-express c-Kit while chronic IM, lose c-Kit and HER-1 in GIST882 cells. GIST882 and GIST430/654 cells have an IC50 0.077 and 0.59 µM to IM respectively. GIST48 have an IC50 0.66 µM to IM, 0.91 µM to amuvatinib [AMU] and 0.67 µM to erlotinib (Erl). Synergistic combinations: GIST882, AMU + Erl (CI 0.20); IM + AMU (CI 0.50), GIST430/654, IM + afatinib (CI 0.39); IM + AMU (CI 0.42), GIST48, IM + afatinib (CI 0.03); IM + AMU (CI 0.04); AMU + afatinib (CI 0.36); IM + Erl (CI 0.63). CONCLUSION: Targeting c-Kit plus HER1 or AXL/c-Met abrogates IM resistance in GIST. In the experiment, the researchers used many compounds, for example, N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3COA of Formula: C23H21N5O3S).

N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3) belongs to benzofurans derivatives. Benzofurans are only weakly aromatic in nature and they are cleaved by many oxidative and reductive conditions. Introduction of benzofurans in organic synthesis, particularly drug synthesis, involves generally the use of their metalated species as nucleophiles in addition reactions or in metal-catalysed cross-coupling reactions.COA of Formula: C23H21N5O3S

Referemce:
Benzofuran – Wikipedia,
Benzofuran | C8H6O – PubChem

Mita, Monica et al. published their research in Cancer Chemotherapy and Pharmacology in 2014 | CAS: 850879-09-3

N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3) belongs to benzofurans derivatives. Benzofurans are compounds with a planar structure having 10 pi electrons that include the lone pair on oxygen atom, which makes it more susceptible to electrophilic attack. Benzofurans have also made significant and distinctive contributions to biology. They exhibit several biological activities that range from antiviral, antimicrobial, antitumor, anti-inflammatory.Formula: C23H21N5O3S

Phase 1B study of amuvatinib in combination with five standard cancer therapies in adults with advanced solid tumors was written by Mita, Monica;Gordon, Michael;Rosen, Lee;Kapoor, Nirmal;Choy, Gavin;Redkar, Sanjeev;Taverna, Pietro;Oganesian, Aram;Sahai, Amarpal;Azab, Mohammad;Bristow, Robert;Tolcher, Anthony W.. And the article was included in Cancer Chemotherapy and Pharmacology in 2014.Formula: C23H21N5O3S This article mentions the following:

Purpose: Amuvatinib is an oral multi-kinase inhibitor that suppresses RAD51, inhibits mutant c-KIT and platelet-derived growth factor receptor alpha, and has synergistic activity with DNA-damaging agents and topoisomerase inhibitors such as etoposide, doxorubicin, and topotecan. We conducted a phase 1B study to estimate the maximum tolerated dose (MTD) levels of amuvatinib with standard chemotherapy regimens and to define the safety profiles of specific amuvatinib + standard regimens. Methods: Five therapies each co-administered with amuvatinib 100-800 mg/day every 21 days were evaluated in treatment-naive or moderately pre-treated subjects: paclitaxel IV followed by carboplatin IV; carboplatin IV followed by etoposide; topotecan IV; docetaxel IV; and erlotinib by mouth. Results: Among 97 treated subjects, no treatment arm reached the MTD. Dose-limiting toxicities included febrile neutropenia and diarrhea. No pharmacokinetic interactions of amuvatinib with any cancer regimens occurred. Of 12/97 (12 %) partial responses overall, 11 were seen in the amuvatinib and paclitaxel/carboplatin or carboplatin/etoposide arms and most commonly in the neuroendocrine (NE), non-small cell lung cancer (NSCLC), and small cell lung cancer (SCLC) tumors. Forty-four subjects (45 %) had stable disease. Adverse events reflected combination treatment and were primarily non-hematol. (fatigue, alopecia, diarrhea, nausea, anorexia) and hematol. (neutropenia, anemia, thrombocytopenia, leukopenia). Pharmacodynamic effects as measured by decreased levels of RAD51 and increased residual DNA damage (53BP1 foci) were seen in skin punch biopsies. Conclusion: Amuvatinib was well tolerated, modulated RAD51, and showed antitumor activity when combined with paclitaxel/carboplatin and carboplatin/etoposide in NE, NSCLC, and SCLC tumors. In the experiment, the researchers used many compounds, for example, N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3Formula: C23H21N5O3S).

N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3) belongs to benzofurans derivatives. Benzofurans are compounds with a planar structure having 10 pi electrons that include the lone pair on oxygen atom, which makes it more susceptible to electrophilic attack. Benzofurans have also made significant and distinctive contributions to biology. They exhibit several biological activities that range from antiviral, antimicrobial, antitumor, anti-inflammatory.Formula: C23H21N5O3S

Referemce:
Benzofuran – Wikipedia,
Benzofuran | C8H6O – PubChem

Qi, Wenqing et al. published their research in BMC Cancer in 2009 | CAS: 850879-09-3

N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3) belongs to benzofurans derivatives. Benzofurans are only weakly aromatic in nature and they are cleaved by many oxidative and reductive conditions. Benzofurans are stable towards alkali and readily polymerize on treatment with sulfuric acid, due to which they are useful for the preparation of low cost chemically relatively inert resins.COA of Formula: C23H21N5O3S

MP470, a novel receptor tyrosine kinase inhibitor, in combination with Erlotinib inhibits the HER family/PI3K/Akt pathway and tumor growth in prostate cancer was written by Qi, Wenqing;Cooke, Larry S.;Stejskal, Amy;Riley, Christopher;Della Croce, Kimiko;Saldanha, Jose W.;Bearss, David;Mahadevan, Daruka. And the article was included in BMC Cancer in 2009.COA of Formula: C23H21N5O3S This article mentions the following:

Background: Prostate cancer is a common disease in men and at present there is no effective therapy available due to its recurrence despite androgen deprivation therapy. The epidermal growth factor receptor family (EGFR/HER1, HER2/neu and HER3)/PI3K/Akt signaling axis has been implicated in prostate cancer development and progression. However, Erlotinib, an EGFR tyrosine kinase inhibitor, has less effect on proliferation and apoptosis in prostate cancer cell lines. In this study, we evaluate whether MP470, a novel receptor tyrosine kinase inhibitor alone or in combination with Erlotinib has inhibitory effect on prostate cancer in vitro and in vivo. Methods: The efficacy of MP470 or MP470 plus Erlotinib was evaluated in vitro using three prostate cancer cell lines by MTS and apoptosis assays. The mol. mechanism study was carried out by phosphorylation antibody array, immunoblotting and immunohistochem. A LNCaP mouse xenograft model was also used to determine the tumor growth inhibition by MP470, Erlotinib or the combination treatments. Results: MP470 exhibits low μM IC50 in prostate cancer cell lines. Additive effects on both cytotoxicity and induction of apoptosis were observed when LNCaP were treated with MP470 in combination with Erlotinib. This combination treatment completely inhibited phosphorylation of the HER family members (HER1, 2, 3), binding of PI3K regulatory unit p85 to HER3 and downstream Akt activity even after androgen depletion. Furthermore, in a LNCaP mouse xenograft model, the MP470-Erlotinib combination produced 30-65% dose-dependent tumor growth inhibition (TGI). Conclusion: We propose that MP470-Erlotinib targets the HER family/PI3K/Akt pathway and may represent a novel therapeutic strategy for prostate cancer. In the experiment, the researchers used many compounds, for example, N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3COA of Formula: C23H21N5O3S).

N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3) belongs to benzofurans derivatives. Benzofurans are only weakly aromatic in nature and they are cleaved by many oxidative and reductive conditions. Benzofurans are stable towards alkali and readily polymerize on treatment with sulfuric acid, due to which they are useful for the preparation of low cost chemically relatively inert resins.COA of Formula: C23H21N5O3S

Referemce:
Benzofuran – Wikipedia,
Benzofuran | C8H6O – PubChem

Choy, Gavin et al. published their research in Cancer Chemotherapy and Pharmacology in 2012 | CAS: 850879-09-3

N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3) belongs to benzofurans derivatives.Benzofuran is one of the most significant oxygen-containing heterocycles consisting of fused benzene and furan ring, which are widely presented in various naturally occurring and synthetically active compounds. Benzofurans have also made significant and distinctive contributions to biology. They exhibit several biological activities that range from antioxidant, antitubercular, antiplasmodial, insecticidal.Computed Properties of C23H21N5O3S

Safety, tolerability, and pharmacokinetics of amuvatinib from three phase 1 clinical studies in healthy volunteers was written by Choy, Gavin;Joshi-Hangal, Rajashree;Oganesian, Aram;Fine, Gil;Rasmussen, Scott;Collier, Joanne;Kissling, James;Sahai, Amarpal;Azab, Mohammad;Redkar, Sanjeev. And the article was included in Cancer Chemotherapy and Pharmacology in 2012.Computed Properties of C23H21N5O3S This article mentions the following:

Purpose: Amuvatinib is a multi-targeted tyrosine kinase inhibitor with activity that also disrupts DNA damage repair through suppression of homologous recombination protein Rad51. Amuvatinib dry-powder capsules (DPC) showed evidence of activity in early Phase 1 cancer studies but low systemic exposure. The purposes of the studies were to investigate the cause of low exposure, develop, and test an alternative formulation with improved exposure, and establish the dose to be tested in future studies in cancer patients. Methods: Three studies were conducted in a total of 58 healthy subjects: a food-effect study using amuvatinib DPC, a single-dose pharmacokinetic study comparing amuvatinib DPC to a new lipid-suspension capsules (LSC), and a multiple-dose pharmacokinetic study using amuvatinib LSC. Results: A high-fat meal administered with amuvatinib DPC increased the rate and extent of absorption compared to the Fasted state, a 183 and 118% increase in the mean C max and AUC0-∞ of amuvatinib, resp. The single-dose pharmacokinetics of amuvatinib LSC resulted in an approx. two-third-fold increased exposure (AUC) compared with amuvatinib DPC. The multiple-dose pharmacokinetics of the amuvatinib LSC 300 mg administered every 8 h exhibited improved accumulation compared with the 12-h regimens and achieved presumed therapeutic level safely with no serious or severe adverse events reported. No subject discontinued treatment due to an adverse event. Conclusion: Amuvatinib LSC, 300 mg every 8 h, is being studied in cancer patients based on the improved exposure and similar safety profile to amuvatinib DPC. A lipid-based formulation approach may be a useful tool for other low aqueous soluble compounds In the experiment, the researchers used many compounds, for example, N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3Computed Properties of C23H21N5O3S).

N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3) belongs to benzofurans derivatives.Benzofuran is one of the most significant oxygen-containing heterocycles consisting of fused benzene and furan ring, which are widely presented in various naturally occurring and synthetically active compounds. Benzofurans have also made significant and distinctive contributions to biology. They exhibit several biological activities that range from antioxidant, antitubercular, antiplasmodial, insecticidal.Computed Properties of C23H21N5O3S

Referemce:
Benzofuran – Wikipedia,
Benzofuran | C8H6O – PubChem

Rausch, Keiko et al. published their research in Cell Reports in 2017 | CAS: 850879-09-3

N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3) belongs to benzofurans derivatives. Benzofuran derivatives are one of the most important oxygen-containing heterocycles. Benzofurans have also made significant and distinctive contributions to biology. They exhibit several biological activities that range from antioxidant, antitubercular, antiplasmodial, insecticidal.Safety of N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide

Screening Bioactives Reveals Nanchangmycin as a Broad Spectrum Antiviral Active against Zika Virus was written by Rausch, Keiko;Hackett, Brent A.;Weinbren, Nathan L.;Reeder, Sophia M.;Sadovsky, Yoel;Hunter, Christopher A.;Schultz, David C.;Coyne, Carolyn B.;Cherry, Sara. And the article was included in Cell Reports in 2017.Safety of N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide This article mentions the following:

Zika virus is an emerging arthropod-borne flavivirus for which there are no vaccines or specific therapeutics. We screened a library of 2,000 bioactive compounds for their ability to block Zika virus infection in three distinct cell types with two different strains of Zika virus. Using a microscopy-based assay, we validated 38 drugs that inhibited Zika virus infection, including FDA-approved nucleoside analogs. Cells expressing high levels of the attachment factor AXL can be protected from infection with receptor tyrosine kinase inhibitors, while placental-derived cells that lack AXL expression are insensitive to this inhibition. Importantly, we identified nanchangmycin as a potent inhibitor of Zika virus entry across all cell types tested, including physiol. relevant primary cells. Nanchangmycin also was active against other medically relevant viruses, including West Nile, dengue, and chikungunya viruses that use a similar route of entry. This study provides a resource of small mols. to study Zika virus pathogenesis. In the experiment, the researchers used many compounds, for example, N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3Safety of N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide).

N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3) belongs to benzofurans derivatives. Benzofuran derivatives are one of the most important oxygen-containing heterocycles. Benzofurans have also made significant and distinctive contributions to biology. They exhibit several biological activities that range from antioxidant, antitubercular, antiplasmodial, insecticidal.Safety of N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide

Referemce:
Benzofuran – Wikipedia,
Benzofuran | C8H6O – PubChem

Jafari, Mohieddin et al. published their research in Nature Communications in 2022 | CAS: 850879-09-3

N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3) belongs to benzofurans derivatives. Many natural or synthetic compounds containing benzofuran skeletons have been found to possess remarkable activity as agrochemicals and pharmaceuticals. Substituted benzofurans find applications such as fluorescent sensors, oxidants, in drug discovery, and in another field of chemistry and agriculture.Reference of 850879-09-3

Bipartite network models to design combination therapies in acute myeloid leukaemia was written by Jafari, Mohieddin;Mirzaie, Mehdi;Bao, Jie;Barneh, Farnaz;Zheng, Shuyu;Eriksson, Johanna;Heckman, Caroline A.;Tang, Jing. And the article was included in Nature Communications in 2022.Reference of 850879-09-3 This article mentions the following:

Combination therapy is preferred over single-targeted monotherapies for cancer treatment due to its efficiency and safety. However, identifying effective drug combinations costs time and resources. We propose a method for identifying potential drug combinations by bipartite network modeling of patient-related drug response data, specifically the Beat AML dataset. The median of cell viability is used as a drug potency measurement to reconstruct a weighted bipartite network, model drug-biol. sample interactions, and find the clusters of nodes inside two projected networks. Then, the clustering results are leveraged to discover effective multi-targeted drug combinations, which are also supported by more evidence using GDSC and ALMANAC databases. The potency and synergy levels of selective drug combinations are corroborated against monotherapy in three cell lines for acute myeloid leukemia in vitro. In this study, we introduce a nominal data mining approach to improving acute myeloid leukemia treatment through combinatorial therapy. In the experiment, the researchers used many compounds, for example, N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3Reference of 850879-09-3).

N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3) belongs to benzofurans derivatives. Many natural or synthetic compounds containing benzofuran skeletons have been found to possess remarkable activity as agrochemicals and pharmaceuticals. Substituted benzofurans find applications such as fluorescent sensors, oxidants, in drug discovery, and in another field of chemistry and agriculture.Reference of 850879-09-3

Referemce:
Benzofuran – Wikipedia,
Benzofuran | C8H6O – PubChem

Mahadevan, D. et al. published their research in Oncogene in 2007 | CAS: 850879-09-3

N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3) belongs to benzofurans derivatives.Benzofuran is one of the most significant oxygen-containing heterocycles consisting of fused benzene and furan ring, which are widely presented in various naturally occurring and synthetically active compounds. Benzofurans have also made significant and distinctive contributions to biology. They exhibit several biological activities that range from antiviral, antimicrobial, antitumor, anti-inflammatory.Electric Literature of C23H21N5O3S

A novel tyrosine kinase switch is a mechanism of imatinib resistance in gastrointestinal stromal tumors was written by Mahadevan, D.;Cooke, L.;Riley, C.;Swart, R.;Simons, B.;Della Croce, K.;Wisner, L.;Iorio, M.;Shakalya, K.;Garewal, H.;Nagle, R.;Bearss, D.. And the article was included in Oncogene in 2007.Electric Literature of C23H21N5O3S This article mentions the following:

KIT or α-platelet-derived growth factor receptor (α-PDGFR) activating mutations are the pathogenic mechanisms that characterize gastrointestinal stromal tumors (GIST). Despite excellent responses to imatinib mesylate (IM), patients are relapsing. We developed an IM-resistant GIST cell line (GIST-R) from the IM-sensitive GIST882 cell line (GIST-S) by growing these cells in IM. Gene expression profiling (GEP) of GIST-S, GIST-R cells and two IM resistant GIST patients demonstrated that KIT is downregulated implying a major role in IM resistance. Instead, GIST-R cells have acquired IM resistance by overexpressing the oncogenic receptor tyrosine kinase – AXL – in a ‘kinase switch’. Further, the two IM resistant GIST patients express AXL and not c-Kit, seen by immunohistochem. (IHC). Real time reverse transcriptase-polymerase chain reaction and Western blotting of the GIST-S and GIST-R cells confirmed the switch from Kit to AXL. In GIST-R, AXL is tyrosine phosphorylated and its ligand growth-arrest-specific gene 6 is overexpressed implying autocrine activation. The kinase switch is associated with a morphol. change from spindle to epithelioid. Mol. modeling of the kinase domain of mutant c-Kit (V654A) and AXL showed no binding to IM but efficient binding to MP470, a novel c-Kit/AXL kinase inhibitor. MP470 synergizes with docetaxel (taxotere) and is cytotoxic to GIST cells. In the experiment, the researchers used many compounds, for example, N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3Electric Literature of C23H21N5O3S).

N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3) belongs to benzofurans derivatives.Benzofuran is one of the most significant oxygen-containing heterocycles consisting of fused benzene and furan ring, which are widely presented in various naturally occurring and synthetically active compounds. Benzofurans have also made significant and distinctive contributions to biology. They exhibit several biological activities that range from antiviral, antimicrobial, antitumor, anti-inflammatory.Electric Literature of C23H21N5O3S

Referemce:
Benzofuran – Wikipedia,
Benzofuran | C8H6O – PubChem

Liu, Ruilong et al. published their research in Nature Communications in 2019 | CAS: 850879-09-3

N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3) belongs to benzofurans derivatives. Benzofurans are compounds with a planar structure having 10 pi electrons that include the lone pair on oxygen atom, which makes it more susceptible to electrophilic attack. Benzofurans are stable towards alkali and readily polymerize on treatment with sulfuric acid, due to which they are useful for the preparation of low cost chemically relatively inert resins.COA of Formula: C23H21N5O3S

Tyrosine phosphorylation activates 6-phosphogluconate dehydrogenase and promotes tumor growth and radiation resistance was written by Liu, Ruilong;Li, Wenfeng;Tao, Bangbao;Wang, Xiongjun;Yang, Zhuo;Zhang, Yajuan;Wang, Chenyao;Liu, Rongzhi;Gao, Hong;Liang, Ji;Yang, Weiwei. And the article was included in Nature Communications in 2019.COA of Formula: C23H21N5O3S This article mentions the following:

6-Phosphogluconate dehydrogenase (6PGD) is a key enzyme that converts 6-phosphogluconate into ribulose-5-phosphate with NADP+ as cofactor in the pentose phosphate pathway (PPP). 6PGD is commonly upregulated and plays important roles in many human cancers, while the mechanism underlying such roles of 6PGD remains elusive. Here we show that upon EGFR activation, 6PGD is phosphorylated at tyrosine (Y) 481 by Src family kinase Fyn. This phosphorylation enhances 6PGD activity by increasing its binding affinity to NADP+ and therefore activates the PPP for NADPH and ribose-5-phosphate, which consequently detoxifies intracellular reactive oxygen species (ROS) and accelerates DNA synthesis. Abrogating 6PGD Y481 phosphorylation (pY481) dramatically attenuates EGF-promoted glioma cell proliferation, tumor growth and resistance to ionizing radiation. In addition, 6PGD pY481 is associated with Fyn expression, the malignancy and prognosis of human glioblastoma. These findings establish a critical role of Fyn-dependent 6PGD phosphorylation in EGF-promoted tumor growth and radiation resistance. In the experiment, the researchers used many compounds, for example, N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3COA of Formula: C23H21N5O3S).

N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3) belongs to benzofurans derivatives. Benzofurans are compounds with a planar structure having 10 pi electrons that include the lone pair on oxygen atom, which makes it more susceptible to electrophilic attack. Benzofurans are stable towards alkali and readily polymerize on treatment with sulfuric acid, due to which they are useful for the preparation of low cost chemically relatively inert resins.COA of Formula: C23H21N5O3S

Referemce:
Benzofuran – Wikipedia,
Benzofuran | C8H6O – PubChem

Mahadevan, D. et al. published their research in Oncogene in 2007 | CAS: 850879-09-3

N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3) belongs to benzofurans derivatives.Benzofuran is one of the most significant oxygen-containing heterocycles consisting of fused benzene and furan ring, which are widely presented in various naturally occurring and synthetically active compounds. Benzofurans have also made significant and distinctive contributions to biology. They exhibit several biological activities that range from antiviral, antimicrobial, antitumor, anti-inflammatory.Electric Literature of C23H21N5O3S

A novel tyrosine kinase switch is a mechanism of imatinib resistance in gastrointestinal stromal tumors was written by Mahadevan, D.;Cooke, L.;Riley, C.;Swart, R.;Simons, B.;Della Croce, K.;Wisner, L.;Iorio, M.;Shakalya, K.;Garewal, H.;Nagle, R.;Bearss, D.. And the article was included in Oncogene in 2007.Electric Literature of C23H21N5O3S This article mentions the following:

KIT or α-platelet-derived growth factor receptor (α-PDGFR) activating mutations are the pathogenic mechanisms that characterize gastrointestinal stromal tumors (GIST). Despite excellent responses to imatinib mesylate (IM), patients are relapsing. We developed an IM-resistant GIST cell line (GIST-R) from the IM-sensitive GIST882 cell line (GIST-S) by growing these cells in IM. Gene expression profiling (GEP) of GIST-S, GIST-R cells and two IM resistant GIST patients demonstrated that KIT is downregulated implying a major role in IM resistance. Instead, GIST-R cells have acquired IM resistance by overexpressing the oncogenic receptor tyrosine kinase – AXL – in a ‘kinase switch’. Further, the two IM resistant GIST patients express AXL and not c-Kit, seen by immunohistochem. (IHC). Real time reverse transcriptase-polymerase chain reaction and Western blotting of the GIST-S and GIST-R cells confirmed the switch from Kit to AXL. In GIST-R, AXL is tyrosine phosphorylated and its ligand growth-arrest-specific gene 6 is overexpressed implying autocrine activation. The kinase switch is associated with a morphol. change from spindle to epithelioid. Mol. modeling of the kinase domain of mutant c-Kit (V654A) and AXL showed no binding to IM but efficient binding to MP470, a novel c-Kit/AXL kinase inhibitor. MP470 synergizes with docetaxel (taxotere) and is cytotoxic to GIST cells. In the experiment, the researchers used many compounds, for example, N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3Electric Literature of C23H21N5O3S).

N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide (cas: 850879-09-3) belongs to benzofurans derivatives.Benzofuran is one of the most significant oxygen-containing heterocycles consisting of fused benzene and furan ring, which are widely presented in various naturally occurring and synthetically active compounds. Benzofurans have also made significant and distinctive contributions to biology. They exhibit several biological activities that range from antiviral, antimicrobial, antitumor, anti-inflammatory.Electric Literature of C23H21N5O3S

Referemce:
Benzofuran – Wikipedia,
Benzofuran | C8H6O – PubChem