Tag: 278.155

Discovery of a Selective, Covalent IRAK1 Inhibitor with Antiproliferative Activity in MYD88 Mutated B-Cell Lymphoma was written by Hatcher, John M.;Yang, Guang;Wang, Li;Ficarro, Scott B.;Buhrlage, Sara;Wu, Hao;Marto, Jarrod A.;Treon, Steven P.;Gray, Nathanael S.. And the article was included in ACS Medicinal Chemistry Letters in 2020.Reference of 903550-26-5 This article mentions the following:

Interleukin 1 (IL-1) receptor-associated kinases (IRAKs) are serine/threonine kinases that play critical roles in initiating the innate immune response against foreign pathogens. Addnl., dysregulation of IRAK1 signaling plays a role in neoplastic disorders. For example, IRAK1 was shown to be important for survival and proliferation in many B-cell lymphomas, including Waldenstr枚m’s macroglobulinemia (WM) and ABC subtype Diffused Large B-cell Lymphoma (DLBCL) cells. Here, we report the discovery of a highly potent and selective covalent inhibitor of IRAK1, JH-X-119-01. Intact protein MS labeling studies confirmed that JH-X-119-01 irreversibly labels IRAK1 at C302. This compound exhibited cytotoxic activity at single digit micromolar concentrations in a panel of WM, DLBCL, and lymphoma cell lines expressing MYD88. Cotreatment of JH-X-119-01 with the BTK inhibitor ibrutinib resulted in synergistic killing effects in these systems. Taken together, JH-X-119-01 represents a highly selective probe of IRAK1 for further development. In the experiment, the researchers used many compounds, for example, 1-(Tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (cas: 903550-26-5Reference of 903550-26-5).

1-(Tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (cas: 903550-26-5) belongs to tetrahydropyran derivatives. Tetrahydropyrans and furans principally constitute as a central motif in diverse medicinally privileged molecules. The most notable anticancer agent, bryostatin, and eribulin are marine macrolides having intriguing tetrahydropyran and furan motif. Reference of 903550-26-5

Referemce:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

Targeting the Allosteric Site of Oncoprotein BCR-ABL as an Alternative Strategy for Effective Target Protein Degradation was written by Shimokawa, Kenichiro;Shibata, Norihito;Sameshima, Tomoya;Miyamoto, Naoki;Ujikawa, Osamu;Nara, Hiroshi;Ohoka, Nobumichi;Hattori, Takayuki;Cho, Nobuo;Naito, Mikihiko. And the article was included in ACS Medicinal Chemistry Letters in 2017.COA of Formula: C14H23BN2O3 This article mentions the following:

Protein degradation technol. based on hybrid small mols. is an emerging drug modality that has significant potential in drug discovery and as a unique method of post-translational protein knockdown in the field of chem. biol. Here, we report the first example of a novel and potent protein degradation inducer that binds to an allosteric site of the oncogenic BCR-ABL protein. BCR-ABL allosteric ligands were incorporated into the SNIPER (Specific and Nongenetic inhibitor of apoptosis protein [IAP]-dependent Protein Erasers) platform, and a series of in vitro biol. assays of binding affinity, target protein modulation, signal transduction, and growth inhibition were carried out. One of the designed compounds, I (SNIPER(ABL)-062), showed desirable binding affinities against ABL1, cIAP1/2, and XIAP and consequently caused potent BCR-ABL degradation In the experiment, the researchers used many compounds, for example, 1-(Tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (cas: 903550-26-5COA of Formula: C14H23BN2O3).

1-(Tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (cas: 903550-26-5) belongs to tetrahydropyran derivatives. Dihydropyrans and tetrahydropyrans are examples of cyclic ethers widespread in nature. There is large number of marine macrolide natural products that contain tetrahydropyran and tetrahydrofuran ring together. For instance, goniodomin A (actin targeting polyether), prorocentrolide (toxin halistatins), and percentotoxineCOA of Formula: C14H23BN2O3

Referemce:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

Discovery of a new class of JMJD6 inhibitors and structure-activity relationship study was written by Wang, Tianqi;Zhang, Rong;Liu, Yang;Fang, Zhen;Zhang, Hailin;Fan, Yan;Yang, Shengyong;Xiang, Rong. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2021.HPLC of Formula: 903550-26-5 This article mentions the following:

JmjC domain-containing protein 6 (JMJD6) has been thought as a potential target for various diseases particularly cancer. However, few selective JMJD6 inhibitors have been reported. In this investigation, mol. docking and biol. activity evaluation were performed to retrieve new JMJD6 inhibitors, which led to the identification of a hit compound, J2. Further structural optimization and structure-activity relationship (SAR) anal. towards J2 were carried out, which gave a new potent JMJD6 inhibitor, 7p. This compound showed an IC50 value of 0.681渭M against JMJD6, but displayed no activity against other tested JmjC domain-containing protein family members, indicating good selectivity (>100 fold). Collectively, this investigation offers a selective JMJD6 inhibitor, which could be taken as a lead compound for subsequent drug discovery targeting JMJD6. In the experiment, the researchers used many compounds, for example, 1-(Tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (cas: 903550-26-5HPLC of Formula: 903550-26-5).

1-(Tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (cas: 903550-26-5) belongs to tetrahydropyran derivatives. Numerous natural products have tetrahydropyran skeleton as the building block for designing new natural products and their derivatives e.g. aplysiatoxins, avermectins, oscillatoxins, talaromycins, latrunculins and acutiphycins. Pyran derivatives such as pyran flavonoids are biologically important. Monosaccharides containing six-membered rings are called pyranose.HPLC of Formula: 903550-26-5

Referemce:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics