Category: 518303-20-3

Jin, Yuanyuan published the artcileThe combination of C-Myc rearrangement and 1q21 gain is associated with poor prognosis in multiple myeloma, Name: 2-((4-(4-Bromophenylsulfonamido)-1-hydroxynaphthalen-2-yl)thio)acetic acid, the publication is Annals of Hematology (2021), 100(5), 1251-1260, database is CAplus and MEDLINE.

The prognostic value of chromosomal 1q21 gain in newly diagnosed multiple myeloma (NDMM) remains controversial. Add-on Myc aberrations may further worsen the outcome. To investigate whether specific genes located at the 1q21 region, such as myeloid cell leukemia 1 (Mcl-1), are involved in NDMM progression, we examined bone marrow cytogenetic abnormalities in 153 patients with NDMM by fluorescence in situ hybridization. Their response to treatment and survival was also analyzed. C-Myc and Mcl-1 expressions in bone marrow samples were analyzed by RT-PCR. The expression of Mcl-1 was evaluated in bone marrow sections by immunohistochem. MM cell lines were transfected with Mcl-1 siRNA. 1q21 gain was present in 55/153 (35.9%) patients and strongly associated with Myc rearrangement (31/153, 20.3%, P = 0.004). A pos. correlation was observed between Myc and Mcl-1 mRNA levels in bone marrow cells from 47 patients (r = 0.57, P < 0.001). The combination of 1q21 gain and Myc rearrangement was associated with poorer overall survival than Myc rearrangement alone (16.8 vs. 27.9 mo, P = 0.077) or 1q21 gain alone (16.8 vs. 60.7 mo, P < 0.01). High Mcl-1 protein expression in bone marrow plasma cells was associated with Myc rearrangement. Mcl-1 silencing by siRNA inhibited Myc protein expression in three myeloma cell lines. Treatment with the small-mol. Mcl-1 inhibitor, UMI-77, produced similar results. Overall, the combination of Myc rearrangement and 1q21 gain was associated with particularly poor prognosis in patients with MM. Furthermore, our data are consistent with Mcl-1-dependent Myc protein activation.

Annals of Hematology published new progress about 518303-20-3. 518303-20-3 belongs to alcohols-buliding-blocks, auxiliary class Apoptosis,Bcl-2, name is 2-((4-(4-Bromophenylsulfonamido)-1-hydroxynaphthalen-2-yl)thio)acetic acid, and the molecular formula is C18H14BrNO5S2, Name: 2-((4-(4-Bromophenylsulfonamido)-1-hydroxynaphthalen-2-yl)thio)acetic acid.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Cen, Xufeng published the artcileTargeting MCL1 to induce mitophagy is a potential therapeutic strategy for Alzheimer disease, Related Products of alcohols-buliding-blocks, the publication is Autophagy (2021), 17(3), 818-819, database is CAplus and MEDLINE.

Mitochondrial dysfunction is associated with the occurrence of a variety of neurodegenerative diseases, especially Alzheimer disease (AD). As a mitochondrial quality control process, mitophagy is greatly inhibited in AD; increasing evidence shows that the induction of mitophagy is an effective therapeutic intervention strategy. However, the lack of more safe, effective, and clear mechanisms for mitophagy inducers has limited the clin. application. In recent studies, we have identified a small mol. compound, UMI-77, that can safely and effectively induce mitophagy. UMI-77 is an established BH3-mimetic for MCL1 and was developed to induce apoptosis in cancer cells. We found that UMI-77 can bind MCL1 and enhance its function as a mitophagy receptor protein, thus enhancing its interaction with LC3A to induce mitophagy. UMI-77 effectively improves the cognitive decline seen in an AD mouse model. Our findings shed light on the novel mechanisms of mitophagy, reveal that MCL1 is a mitophagy receptor that can be targeted to induce mitophagy, and identify MCL1 as a drug target for therapeutic intervention in AD.

Autophagy published new progress about 518303-20-3. 518303-20-3 belongs to alcohols-buliding-blocks, auxiliary class Apoptosis,Bcl-2, name is 2-((4-(4-Bromophenylsulfonamido)-1-hydroxynaphthalen-2-yl)thio)acetic acid, and the molecular formula is C18H14BrNO5S2, Related Products of alcohols-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Chen, Chen published the artcileDesign, synthesis and preliminary bioactivity studies of indomethacin derivatives as Bcl-2/Mcl-1 dual inhibitors, Application of 2-((4-(4-Bromophenylsulfonamido)-1-hydroxynaphthalen-2-yl)thio)acetic acid, the publication is Bioorganic & Medicinal Chemistry (2019), 27(13), 2771-2783, database is CAplus and MEDLINE.

Bcl-2 family proteins, which divides into pro-apoptosis proteins and anti-apoptosis proteins, are involved in cell apoptosis progression. As numerous studies illustrated, targeting Bcl-2 family proteins is more and more attractive and practicable to cancer treatment. In this work, we designed and synthesized a series of indomethacin derivatives as new inhibitors for Bcl-2 family proteins. Our results of binding assay to Bcl-2 proteins, MTT assay and apoptotic assay indicated that some compounds had potent binding affinity to Bcl-2/Mcl-1 but not Bcl-xL. Furthermore, compound 8j showed improved anti-proliferative activity than known Bcl-2 inhibitor WL-276.

Bioorganic & Medicinal Chemistry published new progress about 518303-20-3. 518303-20-3 belongs to alcohols-buliding-blocks, auxiliary class Apoptosis,Bcl-2, name is 2-((4-(4-Bromophenylsulfonamido)-1-hydroxynaphthalen-2-yl)thio)acetic acid, and the molecular formula is C18H14BrNO5S2, Application of 2-((4-(4-Bromophenylsulfonamido)-1-hydroxynaphthalen-2-yl)thio)acetic acid.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Dahlin, Jayme L. published the artcilePAINS in the Assay: Chemical Mechanisms of Assay Interference and Promiscuous Enzymatic Inhibition Observed during a Sulfhydryl-Scavenging HTS, COA of Formula: C18H14BrNO5S2, the publication is Journal of Medicinal Chemistry (2015), 58(5), 2091-2113, database is CAplus and MEDLINE.

Significant resources in early drug discovery are spent unknowingly pursuing artifacts and promiscuous bioactive compounds, while understanding the chem. basis for these adverse behaviors often goes unexplored in pursuit of lead compounds Nearly all the hits from our recent sulfhydryl-scavenging high-throughput screen (HTS) targeting the histone acetyltransferase Rtt109 were such compounds Herein, we characterize the chem. basis for assay interference and promiscuous enzymic inhibition for several prominent chemotypes identified by this HTS, including some pan-assay interference compounds (PAINS). Protein mass spectrometry and ALARM NMR confirmed these compounds react covalently with cysteines on multiple proteins. Unfortunately, compounds containing these chemotypes have been published as screening actives in reputable journals and even touted as chem. probes or preclin. candidates. Our detailed characterization and identification of such thiol-reactive chemotypes should accelerate triage of nuisance compounds, guide screening library design, and prevent follow-up on undesirable chem. matter.

Journal of Medicinal Chemistry published new progress about 518303-20-3. 518303-20-3 belongs to alcohols-buliding-blocks, auxiliary class Apoptosis,Bcl-2, name is 2-((4-(4-Bromophenylsulfonamido)-1-hydroxynaphthalen-2-yl)thio)acetic acid, and the molecular formula is C18H14BrNO5S2, COA of Formula: C18H14BrNO5S2.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

McCallum, Megan M. published the artcileHigh-throughput identification of promiscuous inhibitors from screening libraries with the use of a thiol-containing fluorescent probe, Name: 2-((4-(4-Bromophenylsulfonamido)-1-hydroxynaphthalen-2-yl)thio)acetic acid, the publication is Journal of Biomolecular Screening (2013), 18(6), 705-713, 9 pp., database is CAplus and MEDLINE.

Testing small mols. for their ability to modify cysteine residues of proteins in the early stages of drug discovery is expected to accelerate our ability to develop more selective drugs with lesser side effects. In addition, this approach also enables the rapid evaluation of the mode of binding of new drug candidates with respect to thiol reactivity and metabolism by glutathione. Herein, we describe the development of a fluorescence-based high-throughput assay that allows the identification of thiol-reactive compounds A thiol-containing fluorescent probe, MSTI, was synthesized and used to evaluate small mols. from the Library of Pharmacol. Active Compounds (LOPAC) collection of bioactive mols. LOPAC compounds that are known to react with sulfur nucleophiles were identified with this assay, for example, irreversible protease inhibitors, nitric oxide-releasing compounds and proton-pump inhibitors. The results confirm that both electrophilic and redox reactive compounds can be quickly identified in a high-throughput manner, enabling the assessment of screening libraries with respect to thiol-reactive compounds

Journal of Biomolecular Screening published new progress about 518303-20-3. 518303-20-3 belongs to alcohols-buliding-blocks, auxiliary class Apoptosis,Bcl-2, name is 2-((4-(4-Bromophenylsulfonamido)-1-hydroxynaphthalen-2-yl)thio)acetic acid, and the molecular formula is C18H14BrNO5S2, Name: 2-((4-(4-Bromophenylsulfonamido)-1-hydroxynaphthalen-2-yl)thio)acetic acid.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Zhuang, Chunlin published the artcileRapid Identification of Keap1-Nrf2 Small-Molecule Inhibitors through Structure-Based Virtual Screening and Hit-Based Substructure Search, Recommanded Product: 2-((4-(4-Bromophenylsulfonamido)-1-hydroxynaphthalen-2-yl)thio)acetic acid, the publication is Journal of Medicinal Chemistry (2014), 57(3), 1121-1126, database is CAplus and MEDLINE.

In this study, rapid structure-based virtual screening and hit-based substructure search were utilized to identify small mols. that disrupt the interaction of Keap1-Nrf2. Special emphasis was placed toward maximizing the exploration of chem. diversity of the initial hits while economically establishing informative structure-activity relationship (SAR) of novel scaffolds. Our most potent noncovalent inhibitor exhibits three times improved cellular activation in Nrf2 activation than the most active noncovalent Keap1 inhibitor known to date.

Journal of Medicinal Chemistry published new progress about 518303-20-3. 518303-20-3 belongs to alcohols-buliding-blocks, auxiliary class Apoptosis,Bcl-2, name is 2-((4-(4-Bromophenylsulfonamido)-1-hydroxynaphthalen-2-yl)thio)acetic acid, and the molecular formula is C7H13NO2, Recommanded Product: 2-((4-(4-Bromophenylsulfonamido)-1-hydroxynaphthalen-2-yl)thio)acetic acid.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Liu, Lulu published the artcileDesign, synthesis and biological evaluation of tyrosine derivatives as Mcl-1 inhibitors, Computed Properties of 518303-20-3, the publication is European Journal of Medicinal Chemistry (2020), 112142, database is CAplus and MEDLINE.

The upregulation of the protein myeloid cell leukemia-1 (Mcl-1) is closely associated with various human cancers, which can result in the evasion of apoptosis and a low survival rate. Therefore, developing Mcl-1 inhibitors has become a promising paradigm for cancer therapy. Herein, we designed and synthesized a novel series of tyrosine derivatives, among which compounds (I) (R¹ = 3,5-di-Me-4-Cl-Ph, X = H, R² = OBut, n = 2; R¹ = 3,5-di-Me-4-Cl-Ph, X = H, R² = Ph, n = 1; R¹ = naphthyl, X = Br, R² = 4-Me-benzyl, n = 1) exhibited very high binding affinity to Mcl-1 with K_i values of 0.18, 0.27 and 0.23μM, resp. Interestingly, compound I (R¹ = 3,5-di-Me-4-Cl-Ph, X = H, R² = Ph, n = 1) showed not only potent activity against Mcl-1 but also considerable selectivity over Bcl-2 and Bcl-xL, which was rationalized by mol. docking and fragment-centric topog. mapping (FCTM). It is worth noting that compounds I (R¹ = 3,5-di-Me-4-Cl-Ph, X = H, R² = OBut, n = 2; R¹ = 3,5-di-Me-4-Cl-Ph, X = H, R² = Ph, n = 1; R¹ = naphthyl, X = Br, R² = 4-Me-benzyl, n = 1) displayed potent antiproliferative activity against several cancer cell lines and could induce apoptosis of KM3 and HepG2 cells in a dose-dependent manner.

European Journal of Medicinal Chemistry published new progress about 518303-20-3. 518303-20-3 belongs to alcohols-buliding-blocks, auxiliary class Apoptosis,Bcl-2, name is 2-((4-(4-Bromophenylsulfonamido)-1-hydroxynaphthalen-2-yl)thio)acetic acid, and the molecular formula is C18H14BrNO5S2, Computed Properties of 518303-20-3.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Abulwerdi, Fardokht published the artcileA Novel Small-Molecule Inhibitor of Mcl-1 Blocks Pancreatic Cancer Growth In Vitro and In Vivo, COA of Formula: C18H14BrNO5S2, the publication is Molecular Cancer Therapeutics (2014), 13(3), 565-575, database is CAplus and MEDLINE.

Using a high-throughput screening (HTS) approach, we have identified and validated several small-mol. Mcl-1 inhibitors (SMI). Here, we describe a novel selective Mcl-1 SMI inhibitor, 2 (UMI-77), developed by structure-based chem. modifications of the lead compound 1 (UMI-59). We have characterized the binding of UMI-77 to Mcl-1 by using complementary biochem., biophys., and computational methods and determined its antitumor activity against a panel of pancreatic cancer cells and an in vivo xenograft model. UMI-77 binds to the BH3-binding groove of Mcl-1 with K_i of 490 nmol/L, showing selectivity over other members of the antiapoptotic Bcl-2 family. UMI-77 inhibits cell growth and induces apoptosis in pancreatic cancer cells in a time- and dose-dependent manner, accompanied by cytochrome c release and caspase-3 activation. Coimmunoprecipitation experiments revealed that UMI-77 blocks the heterodimerization of Mcl-1/Bax and Mcl-1/Bak in cells, thus antagonizing the Mcl-1 function. The Bax/Bak-dependent induction of apoptosis was further confirmed using murine embryonic fibroblasts that are Bax- and Bak-deficient. In an in vivo BxPC-3 xenograft model, UMI-77 effectively inhibited tumor growth. Western blot anal. in tumor remnants revealed enhancement of proapoptotic markers and significant decrease of survivin. Collectively, these promising findings show the therapeutic potential of Mcl-1 inhibitors against pancreatic cancer and warrant further preclin. investigations. Mol Cancer Ther; 13(3); 565-75. 2013 AACR.

Molecular Cancer Therapeutics published new progress about 518303-20-3. 518303-20-3 belongs to alcohols-buliding-blocks, auxiliary class Apoptosis,Bcl-2, name is 2-((4-(4-Bromophenylsulfonamido)-1-hydroxynaphthalen-2-yl)thio)acetic acid, and the molecular formula is C18H14BrNO5S2, COA of Formula: C18H14BrNO5S2.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Abulwerdi, Fardokht A. published the artcile3-Substituted-N-(4-Hydroxynaphthalen-1-yl)arylsulfonamides as a Novel Class of Selective Mcl-1 Inhibitors: Structure-Based Design, Synthesis, SAR, and Biological Evaluation, Recommanded Product: 2-((4-(4-Bromophenylsulfonamido)-1-hydroxynaphthalen-2-yl)thio)acetic acid, the publication is Journal of Medicinal Chemistry (2014), 57(10), 4111-4133, database is CAplus and MEDLINE.

Mcl-1, an antiapoptotic member of the Bcl-2 family of proteins, is a validated and attractive target for cancer therapy. Overexpression of Mcl-1 in many cancers results in disease progression and resistance to current chemotherapeutics. Utilizing high-throughput screening, compound I was identified as a selective Mcl-1 inhibitor and its binding to the BH3 binding groove of Mcl-1 was confirmed by several different, but complementary, biochem. and biophys. assays. Guided by structure-based drug design and supported by NMR experiments, comprehensive SAR studies were undertaken and a potent and selective inhibitor, compound II, was designed which binds to Mcl-1 with a K_i of 180 nM. Biol. characterization of II showed that it disrupts the interaction of endogenous Mcl-1 and biotinylated Noxa-BH3 peptide, causes cell death through a Bak/Bax-dependent mechanism, and selectively sensitizes Eμ-myc lymphomas overexpressing Mcl-1, but not Eμ-myc lymphoma cells overexpressing Bcl-2. Treatment of human leukemic cell lines with compound II resulted in cell death through activation of caspase-3 and induction of apoptosis.

Journal of Medicinal Chemistry published new progress about 518303-20-3. 518303-20-3 belongs to alcohols-buliding-blocks, auxiliary class Apoptosis,Bcl-2, name is 2-((4-(4-Bromophenylsulfonamido)-1-hydroxynaphthalen-2-yl)thio)acetic acid, and the molecular formula is C18H14BrNO5S2, Recommanded Product: 2-((4-(4-Bromophenylsulfonamido)-1-hydroxynaphthalen-2-yl)thio)acetic acid.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Anantram, Aarti published the artcileMolecular dynamic simulations on an inhibitor of anti-apoptotic Bcl-2 proteins for insights into its interaction mechanism for anti-cancer activity, Quality Control of 518303-20-3, the publication is Journal of Biomolecular Structure and Dynamics (2019), 37(12), 3109-3121, database is CAplus and MEDLINE.

The first anticancer agents targeting this family of proteins were aimed primarily toward inhibition of Bcl-2. An elevated level of Mcl-1, despite Bcl-2 inhibition, continues to be a cause for resistance in most cancers. However, in silico exploration of Mcl-1 specific drugs and their associated mechanisms have not been clearly elucidated. In order to understand the same, we have carried out docking and mol. dynamic simulations on ABT-263 (Navitoclax), an orally active inhibitor of Bcl-2, Bcl-xL, and Bcl-w proteins; Obatoclax, a pan-Bcl-2 inhibitor as well as Maritoclax, an Mcl-1 specific inhibitor. Docking studies revealed that binding to the hydrophobic grooves is a prerequisite for action on the BCL protein and the binding mechanism and chem. space utilization dictates stability as well as specificity of the inhibitor mol. dynamic simulations showed that on binding, the a-helixes of these proteins exhibited less fluctuations than loop regions, also hydrophobic contacts and hydrogen bonding were observed to be the predominant interactions in the drug-receptor complexes.Communicated by Ramaswamy H. Sarma.

Journal of Biomolecular Structure and Dynamics published new progress about 518303-20-3. 518303-20-3 belongs to alcohols-buliding-blocks, auxiliary class Apoptosis,Bcl-2, name is 2-((4-(4-Bromophenylsulfonamido)-1-hydroxynaphthalen-2-yl)thio)acetic acid, and the molecular formula is C18H14BrNO5S2, Quality Control of 518303-20-3.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts