Category: 882562-40-5

Product Details of 882562-40-5. The protonation of heteroatoms in aromatic heterocycles can be divided into two categories: lone pairs of electrons are in the aromatic ring conjugated system; and lone pairs of electrons do not participate. Compound: 3-(2,5-Dichloropyrimidin-4-yl)-1-(phenylsulfonyl)-1H-indole, is researched, Molecular C18H11Cl2N3O2S, CAS is 882562-40-5, about Structure- and Reactivity-Based Development of Covalent Inhibitors of the Activating and Gatekeeper Mutant Forms of the Epidermal Growth Factor Receptor (EGFR). Author is Ward, Richard A.; Anderton, Mark J.; Ashton, Susan; Bethel, Paul A.; Box, Matthew; Butterworth, Sam; Colclough, Nicola; Chorley, Christopher G.; Chuaqui, Claudio; Cross, Darren A. E.; Dakin, Les A.; Debreczeni, Judit E.; Eberlein, Cath; Finlay, M. Raymond V.; Hill, George B.; Grist, Matthew; Klinowska, Teresa C. M.; Lane, Clare; Martin, Scott; Orme, Jonathon P.; Smith, Peter; Wang, Fengjiang; Waring, Michael J..

A novel series of small-mol. inhibitors has been developed to target the double mutant form of the epidermal growth factor receptor (EGFR) tyrosine kinase, which is resistant to treatment with gefitinib and erlotinib. Our reported compounds also show selectivity over wild-type EGFR. Guided by mol. modeling, this series was evolved to target a cysteine residue in the ATP binding site via covalent bond formation and demonstrates high levels of activity in cellular models of the double mutant form of EGFR. In addition, these compounds show significant activity against the activating mutations, which gefitinib and erlotinib target and inhibition of which gives rise to their observed clin. efficacy. A glutathione (GSH)-based assay was used to measure thiol reactivity toward the electrophilic functionality of the inhibitor series, enabling both the identification of a suitable reactivity window for their potency and the development of a reactivity quant. structure-property relationship (QSPR) to support design.

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The chemical properties of alicyclic heterocycles are similar to those of the corresponding chain compounds. Compound: 3-(2,5-Dichloropyrimidin-4-yl)-1-(phenylsulfonyl)-1H-indole, is researched, Molecular C18H11Cl2N3O2S, CAS is 882562-40-5, about Synthesis and SAR of aminopyrimidines as novel c-Jun N-terminal kinase (JNK) inhibitors, the main research direction is aminopyrimidine derivative preparation antiinflammatory JNK inhibitor.HPLC of Formula: 882562-40-5.

The development of a series of aminopyrimidines, e.g., I, as inhibitors of c-Jun N-terminal kinases is described. The synthesis, in vitro inhibitory values for JNK1, JNK2 and CDK2, and the in vitro inhibitory value for a c-Jun cellular assay were discussed.

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Recommanded Product: 3-(2,5-Dichloropyrimidin-4-yl)-1-(phenylsulfonyl)-1H-indole. The protonation of heteroatoms in aromatic heterocycles can be divided into two categories: lone pairs of electrons are in the aromatic ring conjugated system; and lone pairs of electrons do not participate. Compound: 3-(2,5-Dichloropyrimidin-4-yl)-1-(phenylsulfonyl)-1H-indole, is researched, Molecular C18H11Cl2N3O2S, CAS is 882562-40-5, about Discovery of SY-5609: A Selective, Noncovalent Inhibitor of CDK7. Author is Marineau, Jason J.; Hamman, Kristin B.; Hu, Shanhu; Alnemy, Sydney; Mihalich, Janessa; Kabro, Anzhelika; Whitmore, Kenneth Matthew; Winter, Dana K.; Roy, Stephanie; Ciblat, Stephane; Ke, Nan; Savinainen, Anneli; Wilsily, Ashraf; Malojcic, Goran; Zahler, Robert; Schmidt, Darby; Bradley, Michael J.; Waters, Nigel J.; Chuaqui, Claudio.

CDK7 has emerged as an exciting target in oncol. due to its roles in two important processes that are misregulated in cancer cells: cell cycle and transcription. This report describes the discovery of SY-5609, a highly potent (sub-nM CDK7 Kd) and selective, orally available inhibitor of CDK7 that entered the clinic in 2020 (ClinicalTrials.gov Identifier: NCT04247126). Structure-based design was leveraged to obtain high selectivity (>4000-times the closest off target) and slow off-rate binding kinetics desirable for potent cellular activity. Finally, incorporation of a phosphine oxide as an atypical hydrogen bond acceptor helped provide the required potency and metabolic stability. The development candidate SY-5609 displays potent inhibition of CDK7 in cells and demonstrates strong efficacy in mouse xenograft models when dosed as low as 2 mg/kg.

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Diab, Sarah; Yu, Mingfeng; Wang, Shudong published an article about the compound: 3-(2,5-Dichloropyrimidin-4-yl)-1-(phenylsulfonyl)-1H-indole( cas:882562-40-5,SMILESS:ClC1=NC(C2=CN(C3=C2C=CC=C3)S(=O)(=O)C2=CC=CC=C2)=C(Cl)C=N1 ).Related Products of 882562-40-5. Aromatic heterocyclic compounds can be classified according to the number of heteroatoms or the size of the ring. The authors also want to convey more information about this compound (cas:882562-40-5) through the article.

A review. Cyclin-dependent kinase (CDK) 7 has a unique functional repertoire by virtue of its dual role in transcription and cell cycle progression. Whereas CDK7 is ubiquitously expressed in various types of cancer, its downregulation leads to reduced cell proliferation. Importantly, it is now agreed that targeting transcription selectively limits the synthesis of mRNAs involved in tumor growth without causing an outage of transcription of housekeeping genes. Thus, CDK7 has been considered as a viable therapeutic target in cancer. Indeed, the development of CDK7 inhibitors has gained huge momentum with two mols., CT7001 and SY-1365, currently under clin. development. Herein, we discuss the latest understanding of the role of CDK7 in cancer cells and provide an overview of the pharmacophores of CDK7 inhibitors, their efficacy in various cancer models, and their clin. development.

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Tetrahydroisoquinoline – Wikipedia,
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Most of the natural products isolated at present are heterocyclic compounds, so heterocyclic compounds occupy an important position in the research of organic chemistry. A compound: 882562-40-5, is researched, SMILESS is ClC1=NC(C2=CN(C3=C2C=CC=C3)S(=O)(=O)C2=CC=CC=C2)=C(Cl)C=N1, Molecular C18H11Cl2N3O2SJournal, Article, Journal of Medicinal Chemistry called Structure- and Reactivity-Based Development of Covalent Inhibitors of the Activating and Gatekeeper Mutant Forms of the Epidermal Growth Factor Receptor (EGFR), Author is Ward, Richard A.; Anderton, Mark J.; Ashton, Susan; Bethel, Paul A.; Box, Matthew; Butterworth, Sam; Colclough, Nicola; Chorley, Christopher G.; Chuaqui, Claudio; Cross, Darren A. E.; Dakin, Les A.; Debreczeni, Judit E.; Eberlein, Cath; Finlay, M. Raymond V.; Hill, George B.; Grist, Matthew; Klinowska, Teresa C. M.; Lane, Clare; Martin, Scott; Orme, Jonathon P.; Smith, Peter; Wang, Fengjiang; Waring, Michael J., the main research direction is EGFR activating gatekeeper mutant covalent inhibitor SAR.Synthetic Route of C18H11Cl2N3O2S.

A novel series of small-mol. inhibitors has been developed to target the double mutant form of the epidermal growth factor receptor (EGFR) tyrosine kinase, which is resistant to treatment with gefitinib and erlotinib. Our reported compounds also show selectivity over wild-type EGFR. Guided by mol. modeling, this series was evolved to target a cysteine residue in the ATP binding site via covalent bond formation and demonstrates high levels of activity in cellular models of the double mutant form of EGFR. In addition, these compounds show significant activity against the activating mutations, which gefitinib and erlotinib target and inhibition of which gives rise to their observed clin. efficacy. A glutathione (GSH)-based assay was used to measure thiol reactivity toward the electrophilic functionality of the inhibitor series, enabling both the identification of a suitable reactivity window for their potency and the development of a reactivity quant. structure-property relationship (QSPR) to support design.

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

Name: 3-(2,5-Dichloropyrimidin-4-yl)-1-(phenylsulfonyl)-1H-indole. So far, in addition to halogen atoms, other non-metallic atoms can become part of the aromatic heterocycle, and the target ring system is still aromatic. Compound: 3-(2,5-Dichloropyrimidin-4-yl)-1-(phenylsulfonyl)-1H-indole, is researched, Molecular C18H11Cl2N3O2S, CAS is 882562-40-5, about CDK7 Inhibitors in Cancer Therapy: The Sweet Smell of Success?.

A review. Cyclin-dependent kinase (CDK) 7 has a unique functional repertoire by virtue of its dual role in transcription and cell cycle progression. Whereas CDK7 is ubiquitously expressed in various types of cancer, its downregulation leads to reduced cell proliferation. Importantly, it is now agreed that targeting transcription selectively limits the synthesis of mRNAs involved in tumor growth without causing an outage of transcription of housekeeping genes. Thus, CDK7 has been considered as a viable therapeutic target in cancer. Indeed, the development of CDK7 inhibitors has gained huge momentum with two mols., CT7001 and SY-1365, currently under clin. development. Herein, we discuss the latest understanding of the role of CDK7 in cancer cells and provide an overview of the pharmacophores of CDK7 inhibitors, their efficacy in various cancer models, and their clin. development.

In some applications, this compound(882562-40-5)Name: 3-(2,5-Dichloropyrimidin-4-yl)-1-(phenylsulfonyl)-1H-indole is unique.If you want to know more details about this compound, you can contact with the author or consult more relevant literature.

Reference:
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

SDS of cas: 882562-40-5. The protonation of heteroatoms in aromatic heterocycles can be divided into two categories: lone pairs of electrons are in the aromatic ring conjugated system; and lone pairs of electrons do not participate. Compound: 3-(2,5-Dichloropyrimidin-4-yl)-1-(phenylsulfonyl)-1H-indole, is researched, Molecular C18H11Cl2N3O2S, CAS is 882562-40-5, about Discovery of SY-5609: A Selective, Noncovalent Inhibitor of CDK7. Author is Marineau, Jason J.; Hamman, Kristin B.; Hu, Shanhu; Alnemy, Sydney; Mihalich, Janessa; Kabro, Anzhelika; Whitmore, Kenneth Matthew; Winter, Dana K.; Roy, Stephanie; Ciblat, Stephane; Ke, Nan; Savinainen, Anneli; Wilsily, Ashraf; Malojcic, Goran; Zahler, Robert; Schmidt, Darby; Bradley, Michael J.; Waters, Nigel J.; Chuaqui, Claudio.

CDK7 has emerged as an exciting target in oncol. due to its roles in two important processes that are misregulated in cancer cells: cell cycle and transcription. This report describes the discovery of SY-5609, a highly potent (sub-nM CDK7 Kd) and selective, orally available inhibitor of CDK7 that entered the clinic in 2020 (ClinicalTrials.gov Identifier: NCT04247126). Structure-based design was leveraged to obtain high selectivity (>4000-times the closest off target) and slow off-rate binding kinetics desirable for potent cellular activity. Finally, incorporation of a phosphine oxide as an atypical hydrogen bond acceptor helped provide the required potency and metabolic stability. The development candidate SY-5609 displays potent inhibition of CDK7 in cells and demonstrates strong efficacy in mouse xenograft models when dosed as low as 2 mg/kg.

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

The preparation of ester heterocycles mostly uses heteroatoms as nucleophilic sites, which are achieved by intramolecular substitution or addition reactions. Compound: 3-(2,5-Dichloropyrimidin-4-yl)-1-(phenylsulfonyl)-1H-indole( cas:882562-40-5 ) is researched.Safety of 3-(2,5-Dichloropyrimidin-4-yl)-1-(phenylsulfonyl)-1H-indole.Diab, Sarah; Yu, Mingfeng; Wang, Shudong published the article 《CDK7 Inhibitors in Cancer Therapy: The Sweet Smell of Success?》 about this compound( cas:882562-40-5 ) in Journal of Medicinal Chemistry. Keywords: review pharmacophore CT7001 SY1365 antitumor CDK7 cancer. Let’s learn more about this compound (cas:882562-40-5).

A review. Cyclin-dependent kinase (CDK) 7 has a unique functional repertoire by virtue of its dual role in transcription and cell cycle progression. Whereas CDK7 is ubiquitously expressed in various types of cancer, its downregulation leads to reduced cell proliferation. Importantly, it is now agreed that targeting transcription selectively limits the synthesis of mRNAs involved in tumor growth without causing an outage of transcription of housekeeping genes. Thus, CDK7 has been considered as a viable therapeutic target in cancer. Indeed, the development of CDK7 inhibitors has gained huge momentum with two mols., CT7001 and SY-1365, currently under clin. development. Herein, we discuss the latest understanding of the role of CDK7 in cancer cells and provide an overview of the pharmacophores of CDK7 inhibitors, their efficacy in various cancer models, and their clin. development.

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Tetrahydroisoquinoline – Wikipedia,
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Heterocyclic compounds can be divided into two categories: alicyclic heterocycles and aromatic heterocycles. Compounds whose heterocycles in the molecular skeleton cannot reflect aromaticity are called alicyclic heterocyclic compounds. Compound: 882562-40-5, is researched, Molecular C18H11Cl2N3O2S, about Covalent targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors, the main research direction is THZ531 CDK12 CDK13 inhibitor transcription cancer.Formula: C18H11Cl2N3O2S.

Cyclin-dependent kinases 12 and 13 (CDK12 and CDK13) play critical roles in the regulation of gene transcription. However, the absence of CDK12 and CDK13 inhibitors has hindered the ability to investigate the consequences of their inhibition in healthy cells and cancer cells. Here we describe the rational design of a first-in-class CDK12 and CDK13 covalent inhibitor, THZ531. Co-crystallization of THZ531 with CDK12-cyclin K indicates that THZ531 irreversibly targets a cysteine located outside the kinase domain. THZ531 causes a loss of gene expression with concurrent loss of elongating and hyperphosphorylated RNA polymerase II. In particular, THZ531 substantially decreases the expression of DNA damage response genes and key super-enhancer-associated transcription factor genes. Coincident with transcriptional perturbation, THZ531 dramatically induced apoptotic cell death. Small mols. capable of specifically targeting CDK12 and CDK13 may thus help identify cancer subtypes that are particularly dependent on their kinase activities.

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

Category: tetrahydroisoquinoline. The reaction of aromatic heterocyclic molecules with protons is called protonation. Aromatic heterocycles are more basic than benzene due to the participation of heteroatoms. Compound: 3-(2,5-Dichloropyrimidin-4-yl)-1-(phenylsulfonyl)-1H-indole, is researched, Molecular C18H11Cl2N3O2S, CAS is 882562-40-5, about Structure-activity relationship study of THZ531 derivatives enables the discovery of BSJ-01-175 as a dual CDK12/13 covalent inhibitor with efficacy in Ewing sarcoma. Author is Jiang, Baishan; Jiang, Jie; Kaltheuner, Ines H.; Iniguez, Amanda Balboni; Anand, Kanchan; Ferguson, Fleur M.; Ficarro, Scott B.; Seong, Bo Kyung Alex; Greifenberg, Ann Katrin; Dust, Sofia; Kwiatkowski, Nicholas P.; Marto, Jarrod A.; Stegmaier, Kimberly; Zhang, Tinghu; Geyer, Matthias; Gray, Nathanael S..

Development of inhibitors targeting CDK12/13 is of increasing interest as a potential therapy for cancers as these compounds inhibit transcription of DNA damage response (DDR) genes. We previously described THZ531, a covalent inhibitor with selectivity for CDK12/13. In order to elucidate structure-activity relationship (SAR), we have undertaken a medicinal chem. campaign and established a focused library of THZ531 analogs. Among these analogs, BSJ-01-175 demonstrates exquisite selectivity, potent inhibition of RNA polymerase II phosphorylation, and downregulation of CDK12-targeted genes in cancer cells. A 3.0 Å co-crystal structure with CDK12/CycK provides a structural rational for selective targeting of Cys1039 located in a C-terminal extension from the kinase domain. With moderate pharmacokinetic properties, BSJ-01-175 exhibits efficacy against an Ewing sarcoma tumor growth in a patient-derived xenograft (PDX) mouse model following 10 mg/kg once a day, i.p. administration. Taken together, BSJ-01-175 represents the first selective CDK12/13 covalent inhibitor with in vivo efficacy reported to date.

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