2′,3′-Didesoxycytidin. 1B, fig. Lymphoma Non. 1 Selectivity profile of I-BET151, iBET-BD1 (GSK778), and iBET-BD2 (GSK046). Potent, selective and cell-permeable inhibitors of protein function ("chemical probes") are valued reagents in both fundamental and applied biological research, and they are essential for the early stages of drug discovery by allowing preclinical target validation in both academic and industrial laboratories. ≥98% (HPLC)GSK778 ( iBET-BD1 ) Catalog No. (C) X-ray crystal structure of I-BET151 in. COO/ COA. WGK. 11 - Combustible Solids. 2451862-42-1 related products. Their affinities for the individual bromodomains of the BET family were initially determined by TR-FRET (Fig. Available to order from Sigma-Aldrich. In contrast to other reported domain-selective molecules, these compounds showed little binding to bromodomains. Applications Products Services Documents Support. ( A ) Schematic of the BET bromodomain proteins and chemical structures. Email. GSK778 Hydrochloride is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. Despite their profound preclinical efficacy, the clinical utility of pan-inhibitors is limited due to observed cytotoxicicities. Indeed, in the last 30 years a limited progress has been made in GBM treatment with current first-line standards-of-care. Developing BDII selective compounds was far more challenging, and only a handful of BDII selective inhibitors have been developed to date (Figure 1). Some, such as ABBV-744 and GSK778, are optimized for greater selectivity for one of two distinct BET protein bromodomains in an effort to improve therapeutic indices [55, 56]. Phylogenetic tree of the human bromodomain-containing protein subgroups. Chemical structures of the BD1/BD2-selective BET inhibitors discussed: (A) GSK778, (B) GSK046, (C) ABBV-744, and (D) SJ432. All Photos (1) Documents. COO/ COA. All products from TargetMol are for Research Use. 11 - Combustible Solids. GSK778 Hydrochloride ≥98% (HPLC); Synonyms: 4-{2-(Methoxymethyl)-1-[(R)-1-phenylethyl]-8-[(S)-pyrrolidin-3-ylmethoxy]-1H-imidazo[4,5-c]quinolin-7-yl}-3,5. ≥98% (HPLC) All Photos (1)GSK778 Hydrochloride is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. GSK778 (iBET-BD1) is a strong BD1 bromodomain inhibitor of the BET proteins, with IC50 value of 75. All Photos (1) Documents. BRD4. GSK778 (iBET-BD1) is an analogue of I-BET151 with good potency against BET BD1 (IC 50 = 40 nM) and similar selectivity to LT052 (150-fold) over BD2 [48]. BRD4 inhibitors effectively penetrate the blood-brain barrier and target glioma tumor tissues but have little effect on normal brain tissues. The BD1-selective inhibitor GSK778 exhibited similar transcriptional effects compared to pan-BET inhibitors in cancer cells, consistent with previous studies showing that BD1 plays the dominant role in maintaining established transcriptional programs (Picaud et al. 6swo: c-terminal bromodomain of human brd2 with ibet-bd1 (gsk778)BRD3. GSK778 Hydrochloride. If not otherwise indicated, cells were pretreated with I-BET151, iBET-BD1,. ≥98% (HPLC)Herein, GSK778 and GSK046 are referred to as iBET-BD1 and iBET-BD2, respectively. Domain-Selective Targeting (BD1 or BD2 Targeting) The BET protein family of BCPs comprise the ubiquitously expressed BRD2, BRD3, and BRD4 and the testis-restricted BRDT, all of which harbor two highly conserved tandem bromodomains, BD1 and BD2, allowing them to. Phylogenetic tree of the human bromodomain-containing protein subgroups. +86-21-51987688 Crystal structure of GSK778 complexed with BRD4-BD1 (Fig. I-BET151 (GSK1210151A), iBET-BD1 (GSK778) and iBET-BD2 (GSK046) were provided by GlaxoSmithKline plc (GSK, London, UK). GSK778 Hydrochloride ≥98% (HPLC); Synonyms: 4-{2-(Methoxymethyl)-1-[(R)-1-phenylethyl]-8-[(S)-pyrrolidin-3-ylmethoxy]-1H-imidazo[4,5-c]quinolin-7-yl}-3,5. GSK778 Hydrochloride ≥98% (HPLC); Synonyms: 4-{2-(Methoxymethyl)-1-[(R)-1-phenylethyl]-8-[(S)-pyrrolidin-3-ylmethoxy]-1H-imidazo[4,5-c]quinolin-7-yl}-3,5. GSK778 (iBET-BD1) is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. GSK778 Hydrochloride. Herein, GSK778 and GSK046 are referred to as iBET-BD1 and iBET-BD2, respectively. GSK778 Hydrochloride ≥98% (HPLC); Synonyms: 4-{2-(Methoxymethyl)-1-[(R)-1-phenylethyl]-8-[(S)-pyrrolidin-3-ylmethoxy]-1H-imidazo[4,5-c]quinolin-7-yl}-3,5. In human whole blood and MV-4–11 cells, selective inhibition of GSK778 against BD1 retains the anti-inflammatory and antiproliferative phenotype features of pan-BET inhibition. MS EN. GSK778 Hydrochloride. 00. , 2010), I-BET762 (Nicodeme et al. gov or . SML3234. In contrast to other reported domain-selective molecules, these compounds showed little binding to bromodomains. GSK778, a potent pan-D1 inhibitor, was reported by Gilan et al. GSK778 Hydrochloride ≥98% (HPLC); Synonyms: 4-{2-(Methoxymethyl)-1-[(R)-1-phenylethyl]-8-[(S)-pyrrolidin-3-ylmethoxy]-1H-imidazo[4,5-c]quinolin-7-yl}-3,5. R. 1iBET-BD1 (GSK778) Following the initial report of the biological activity of iBET-BD1 and iBET-BD2, 19 Wellaway et al. Email. Find (s)-1-phenylethyl (r)-acetoxyphenylacetate and related products for scientific research at MilliporeSigmaGSK778 Hydrochloride is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. Their affinities for the individual bromodomains of the BET family were initially determined by TR-FRET (Fig. TC EN. Available to order from Sigma-Aldrich. GSK778 hydrochloride hydrochloride phenocopies the effects of pan-BET inhibitors in cancer models[1]. GSK778 inhibits proliferation, induces a cell cycle arrest and Apoptosis . The calculations of the energy contributions of individual residues demonstrate that residues corresponding to (BD1, BD2) generate significant energy difference in binding of SG3-179, GSK778, and. (A) Schematic of the BET bromodomain proteins and chemical structures. In addition, while GSK778 phenocopied I-BET151 in terms of antiproliferative effects on a range of human cancer cells, GSK046 was less effective. GSK778 (iBET-BD1) potently inhibits numerous cancer cells proliferation, inducing cell cycle arrest and apoptosis. Email. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) < 2. E-newsletter Get updates ,discounts and special offers. Email. Copy Link. GSK778 (iBET-BD1) potently inhibits numerous cancer cells proliferation, inducing cell cycle arrest and apoptosis. 5 (LPS-PBMC assay) ≤ 10 µM. GSK778. (B). For example, whereas a BD1-selective inhibitor (GSK778) showed similar phenocopies of pan BETis in cancers, a BD2-selective inhibitor (GSK046) showed better effectiveness in inflammatory and autoimmune diseases 2. All Photos (1) Documents. 39 Proteolysis targeting chimeras. Herein, GSK778 and GSK046 are referred to as iBET-BD1 and iBET-BD2, respectively. Email. GSK778 phenocopied the effects of pan-BET inhibitors in cancer models. GSK778 Hydrochloride. 09-Sep-2023. Glucocorticoid Receptor Antagonist/Modulator. Solubility: Soluble in DMSO. SGC Toronto. However, distinct from BD1-selective and pan-BET inhibitors, the BD2. Among this class, RVX-208 mainly blocks BD2 function [99], whereas GSK778 is a BD1 selective inhibitor [99]. Catalog No. GSK778 phenocopies the effects of pan-BET inhibitors in cancer models. BET BD1 related products. Storage Class Code. 3; Cell. Email. You can also browse global suppliers,vendor,prices,Price,manufacturers of GSK778(2451862-42-1). Heat Shock Protein Research Products. Applications Products Services Documents Support. Miransertib target all three Akt isoforms by blocking…. Federal government websites often end in . ([email protected]) under a material transfer agreement with GSK. GSK778 (iBET-BD1) potently inhibits numerous cancer cells proliferation, inducing cell cycle arrest and apoptosis. MedChemExpress provides thousands of inhibitors, modulators and agonists with high purity and quality, excellent customer reviews, precise and professional product citations, tech support and prompt delivery. Copy Link. To explore the individual functional contributions of BD1 and BD2 in biology and therapy, selective BD1 and BD2 inhibitors have been developed: GSK778 and GSK046 (termed iBET-BD1 and iBET-BD2, respectively) . ChemicalBook あなたのためにGSK778(2451862-42-1)の化学的性質を提供して、融点、価格、蒸気圧、沸点、毒性、比重、沸点、密度、分子式、分子量、物理的な性質、毒性 税関のコードなどの情報、同時にあなたは更にGSK778(2451862-42-1)の製品の全世界の供給商にブラウズすることができて、生産企業と生産. Sigma-Aldrich. (B) Compound binding to the individual bromodomains of BD1 (orange) and BD2 (cyan) of BET tandem bromodomains in TR-FRET assays. ≥98% (HPLC) All Photos (1)GSK778 (iBET-BD1) هو مثبط قوي وانتقائي BD1 bromodomain لبروتينات BET ، مع IC50s 75 نانومتر (BRD2 BD1) ، 41 نانومتر (BRD3 BD1) ، 41 نانومتر (BRD4 BD1) ، و 143 نانومتر (BRDT BD1) ، على التوالى. GSK778 reduces the production of anti-keyhole limpet. 6SWN: N-TERMINAL BROMODOMAIN OF HUMAN BRD4 WITH iBET-BD1 (GSK778) PDB ID: 6SWN Download: MMDB ID: 192697: PDB Deposition Date: 2019/9/22: Updated in MMDB: 2021/02: Experimental Method: x-ray diffraction. 2 Relevant identified uses of the substance or mixture and uses advised against; Identified uses: For research use only, not for human or veterinary use. Your information is safe with us. In contrast to pan-BET proteins inhibitors, these selective BET proteins inhibitors of BD1 or BD2 are characterizedCas No. The. , 2012). Email: Sales@ChemShuttle. SML3234. ≥98% (HPLC) All Photos (1)GSK778 Hydrochloride is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. At. Fax: +1 510. Available to order from Sigma-Aldrich. 4. Email. SML3234. ChemicalBook provide Chemical industry users with GSK778 Boiling point Melting point,GSK778 Density MSDS Formula Use,If You also need to GSK778 Other information,welcome to contact us. ZA EN. Available to order from Sigma-Aldrich. Drugs that inhibit both bromodomains equally have shown efficacy in certain malignant and inflammatory conditions. Preis und Verfügbarkeit anzeigen. Products are for research use only. Lagerklassenschlüssel. Additionally, while GSK778 phenocopied I-BET151 in terms of anti-proliferative effects on a range of human cancer cells, GSK046 was less effective. All Photos (1) Documents. 14 Whereas a pan-BET inhibitor impeded differentiation of oligodendrocytes, olinone induced this process. IC₅₀ & Target BRD2 BD1 75 nM (IC50) BRD3 BD1 41 nM. Pharmacological inhibition of BET BDs using the chemical probes JQ1 (Filippakopoulos et al. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) < 2. If not otherwise indicated, cells were pretreated with I-BET151, iBET-BD1, iBET-BD2 or vehicle (DMSO) for 48 hours, irradiated with 0 or 6 Gy, and incubated for additional time intervals with concurrent drug. • Xanthine derivatives bind to BD1 with 10 times the affinity (Gilan et al. GlaxoSmithKline; BRD2, BRD3, BRD4, BRDT (BD2) GSK046; pIC50 = 7. GSK778 (iBET-BD1) is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. It achieves this complex task by recruiting BRD4, via a pan-BET ligand (JQ1), to the GAA repeats by using a sequence-selective DNA-binding polyamide. 5 (LPS-PBMC assay) <10: 8 GSK620 (BD2) pIC50 = 7. COO/ COA. e. GSK778 (iBET-BD1) is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. GSK778 (iBET-BD1) is a potent and selective BD1 bromodomain inhibitor of the BET proteins, with IC50s of 75 nM (BRD2 BD1), 41 nM (BRD3 BD1), 41 nM (BRD4 BD1), and 143 nM (BRDT BD1), respectively. 1B, fig. It reduces relapse rate and disease progression in Multiple Sclerosis. GSK778 also displayed strong anti-cancer effects in vivo, prolonging the survival of mice carrying an aggressive form of AML at only 15 mg/kg. COO/ COA. Recently, inhibitors were developed that selectively target the first (BD1) and second (BD2) bromodomain of the BET proteins (iBET-BD1 [GSK778] and iBET-BD2 [GSK046]). WGK. 14 GSK778, another pan-D1-selective inhibitor (Figure 1A), was recently reported. All Photos (1) SML3234. GSK778 Hydrochloride. GSK778 phenocopies the. toronto@thesgc. The calculations of the energy contributions of individual residues demonstrate that residues corresponding to (BD1, BD2) generate significant energy difference in binding of SG3-179, GSK778, and. Meanwhile, GSK778 has IC 50 s of 75 nM (BRD2 BD1), 41 nM (BRD3 BD1), 41 nM (BRD4 BD1), and 143 nM (BRDT BD1), respectively. GSK778 (iBET-BD1) is a potent and selective BD1 bromodomain inhibitor of the BET proteins, with IC50s of 75 nM (BRD2 BD1), 41 nM (BRD3 BD1), 41 nM (BRD4 BD1), and 143 nM (BRDT BD1), respectively. GSK778 (iBET-BD1) potently inhibits numerous cancer cells. 1 ± 0. ≥98% (HPLC)Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years). WGK 3. Glatiramer acetate is a mixture of synthetic peptides randomly composed of glutamic acid, lysine, alanine, and tyrosine. GSK778 (iBET-BD1) is a potent and selective inhibitor of the BD1 bromine domain of the BET protein,IC50 The values are 75 nM (BRD2 BD1), 41 nM (BRD3 BD1), 41 nM (BRD4 BD1), and 143 nM (BRDT BD1). Copy Link. 6SWN, 6SWO, 6SWP, 6SWQ. Email. 6147. The calculations of the energy contributions of individual residues demonstrate that residues corresponding to (BD1, BD2) generate significant energy difference in binding of SG3-179, GSK778, and. , 2020; Gilan et al. The BD2 selective inhibitor RVX-208 could significantly decrease atherosclerosis in hyperlipidemic apolipoprotein E-deficient mice 14 , and increase high-density lipoprotein cholesterol as well as apolipoprotein A-1 in monkeys 15 . ChemScene Provide GSK778(CAS 2451862-42-1)In-stock or Backordered impurities,Bulk custom synthesis,Formular C30H33N5O3,MW 511. 4 D and E) shows that our BD1-selective and BD2-selective DECL-derived inhibitors each occupy the same KAc pocket as GSK778 but also access adjacent grooves that differ between the two domain types. 65 ABBV-744 shows potent anti-proliferative effects against. Applications Products Services Documents Support. GSK778 (iBET-BD1) is a potent and selective BD1 bromodomain inhibitor of the BET proteins, with IC50s of 75 nM (BRD2 BD1), 41 nM (BRD3 BD1), 41 nM (BRD4 BD1), and 143 nM (BRDT BD1), respectively. Available to order from Sigma-Aldrich. All. Storage Class Code. Safety Information. Copy Link. 33DFTG (TD139) $21. 00. GSK778 Hydrochloride is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. (B) Compound binding to the individual bromodomains of BD1 (orange) and BD2 (cyan) of BET tandem bromodomains in TR-FRET assays. GSK778 (iBET-BD1) potently inhibits numerous cancer cells proliferation, inducing cell cycle arrest and apoptosis. GSK778: CAS Registry Number: 2451862-42-1: Molecular Weight: 511. Comprar GSK778 hydrochloride na CymitQuimica a partir de 181,0 € Iniciar Sessão Criar uma conta. SML3234. Chemical Structure GSK778. E-newsletter Get updates ,discounts and special offers. All Photos (1) Documents. Recently, BET proteins inhibitors that selectively target BD1 (GSK778, MS-436, Olinone, and BI-2536) and BET proteins inhibitors that selectively target BD2 (GSK046, RVX-208, RVX-297, ABBV-744) have been developed [42-47]. Applications Products Services Documents Support. GSK778. Safety Information. GSK778 (iBET-BD1) is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. GB EN. ≥98% (HPLC) All Photos (1)MS40224, and GSK77825. LT EN. Louis Gilman July 17, 2023. GSK778 is a potent and selective inhibitor of BD1 bromodomain such as BRD2 BD1 (IC50s = 75 nM), BRD3 BD1 (IC50s = 41 nM), BRD4 BD1 (IC50s = 41 nM), and BRDT BD1 (IC50s = 143 nM). GSK778 phenocopies the effects of pan-BET inhibitors in cancer models [1]. Solubility: Soluble in DMSO. GSK778 (iBET-BD1) potently inhibits numerous cancer cells proliferation, inducing cell cycle arrest and apoptosis. , Suite 700 Toronto, ON, M5G 1L7 Canada +1 416-946-0237. 0; BRD4 (BD2) pKd = 5. Available to order from Sigma-Aldrich. Find here details of companies selling GSK778, for your purchase requirements. GSK778 Hydrochloride ≥98% (HPLC); Synonyms: 4-{2-(Methoxymethyl)-1-[(R)-1-phenylethyl]-8-[(S)-pyrrolidin-3-ylmethoxy]-1H-imidazo[4,5-c]quinolin-7-yl}-3,5. GSK778 Hydrochloride. The calculations of the energy contributions of individual residues demonstrate that residues corresponding to (BD1, BD2) generate significant energy difference in binding of SG3-179, GSK778, and. GSK778 phenocopies the. Potency in Cells and Cellular Target Engagement: GSK778 engages the target in HEK293 cells: pIC50 = 7. LY EN. GSK778 (68), yielded by introducing an additional pyrrolidine to compound 19 (Fig. Applications Products Services Documents Support. GSK778 phenocopies the. CPI-0610 is another second-generation BET inhibitor with a molecular structure similar. GM6001. Applications Products Services Documents Support. GSK778 (iBET-BD1) potently inhibits numerous cancer cells proliferation, inducing cell cycle arrest and apoptosis. Particularly, GSK778 has a more pronounced effect on the growth and viability of MDA-453, MOLM-13, K562, MV4-11, THP-1, and MDA-MB-231 cells. . Email. COO/ COA. GSK778 is a potent and selective inhibitor of BD1 bromodomain such as BRD2 BD1 (IC50s = 75 nM), BRD3 BD1 (IC50s = 41 nM), BRD4 BD1 (IC50s = 41 nM), and BRDT BD1 (IC50s = 143 nM). On the basis of sequence homology, BCPs are classified into eight different subgroups (families). ChemicalBook 为您提供FREEBASE(2451862-42-1)的化学性质，熔点，沸点，密度，分子式，分子量，物理性质，毒性，结构式，海关编码等信息，同时您还可以浏览FREEBASE(2451862-42-1)产品的价格，供应商，贸易商，生产企业和生产厂家，最后FREEBASE(2451862-42-1)的中文，英文，用途，CAS，上下游产品信息可能也是您. Open in a separate window. Applications Products Services Documents Support. 11 - Combustible Solids. SynTEF1, a prototype synthetic genome reader/regulator (SynGR), was designed to target GAA triplet repeats and restore the expression of frataxin (FXN) in Friedreich’s ataxia patients. amni) under a material transfer agreement with GSK. GSK778 Hydrochloride. 8300 Cypress Creek Parkway, Suite 450 Houston. GSK778 reduces the production of anti-keyhole limpet. BA EN. Sigma-Aldrich. We do not sell to patients. GSK778 Catalog No. GSK778 Hydrochloride is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. Available to order from Sigma-Aldrich. , 2013). Shelf Life: >3 years if stored properly. They are useful assets for example, in phenotypic assays, or as a starting point for medicinal chemistry campaigns. However, recent reports of potent and selective pan-BET BD1 and pan-BET BD2 inhibitors have been reported including ABBV-744, 21 GSK778, and GSK046. GSK778 hydrochloride hydrochloride phenocopies the effects of pan-BET inhibitors in cancer models[1]. Available to order from Sigma-Aldrich. iBET-BD1 showed a selectivity of ≥130-fold for BRD4 BD1, and iBET-BD2. In addition, while GSK778 phenocopied I-BET151 in terms of antiproliferative effects on a range of human cancer cells, GSK046 was less effective. GSK778 (iBET-BD1) is a potent and selective BD1 bromodomain inhibitor of the BET proteins, with IC 50 s of 75 nM (BRD2 BD1), 41 nM (BRD3 BD1), 41 nM (BRD4 BD1), and 143 nM (BRDT BD1), respectively. GSK778 Hydrochloride. 1 Among these, bromodomain and extraterminal (BET) proteins constitute a unique group with four family members, bromodomain-containing protein 4 (BRD4), BRD3, BRD2, and. HY-136570 10mg GSK778 CAS: 2451862-42-1 GSK778 (iBET-BD1) is a potent and selective BD1 bromodomain inhibitor of the BET proteins, with IC50s of 75 nM (BRD2 BD1), 41 nM (BRD3 BD1), 41 nM (BRD4 BD1), and 143 nM (BRDT BD1), respectively. At. Another report showed that BD2-selective BET family inhibitors exhibited good efficacies in treating prostate cancer 22. It achieves this complex task by recruiting BRD4, via a pan-BET ligand (JQ1), to the GAA repeats by using a sequence-selective DNA-binding polyamide. GSK778 (iBET-BD1) is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. COO/ COA. 1. Available to order from Sigma-Aldrich. GSK778 Hydrochloride ≥98% (HPLC); Synonyms: 4-{2-(Methoxymethyl)-1-[(R)-1-phenylethyl]-8-[(S)-pyrrolidin-3-ylmethoxy]-1H-imidazo[4,5-c]quinolin-7-yl}-3,5. ≥98% (HPLC)GSK778 Hydrochloride is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. ChemicalBook 致力于为化学行业用户提供FREEBASE的性质、化学式、分子式、比重、密度,同时也包括FREEBASE的沸点、熔点、MSDS、用途、作用、毒性、价格、生产厂家、用途、上游原料、下游产品等信息。 Recently, Gilan et al. For research use only. SML3234. 6 GSK789 (BD1) IC50= 125 nM (MV-4−11 cells) <10: GSK791. Storage Class Code. In spite of the structural similarity to RVX-208, RVX-297 has demonstrated a different pharmacodynamical profile, as well as distinct cellular and biological activity which was elucidated in the. The two tandem. 3 Details of the supplier of the safety data sheet; Company: Abmole Bioscience Inc. Before sharing sensitive information, make sure you’re on a federal government site. Molecular Formula: C30H33N5O3. Their affinities for the individual bromodomains of the BET family were initially determined by TR-FRET (Fig. Using these molecules, Gilan et al. We do not sell to patients. All Photos (1) Documents. To date, 61 bromodomains have been identified in 46 diverse proteins in human cells (Filippakopoulos et al. 7 B) indicated that GSK778 maintains all of the critical interactions of I-BET151 with BRD4-BD1, including the hydrogen bonding interaction of the 3,5-dimethylisoxazole moiety with the conserved Asn140, the hydrophobic interaction of the aryl ring of the α-methylbenzyl group with the. Available to order from Sigma-Aldrich. IL EN. , 2016). GSK778 (iBET-BD1) is a potent and selective BD1 bromodomain inhibitor of the BET proteins, with IC 50 s of 75 nM (BRD2 BD1), 41 nM (BRD3 BD1), 41 nM (BRD4 BD1), and 143 nM (BRDT BD1), respectively. • GSK778 exhibits >130-fold BD1 selectivity over BD2 due to BD1 Asp144/His433 displacement (Kharenko et al. GSK778 phenocopies the effects of pan- BET inhibitors in cancer models. GSK778 Hydrochloride. 27, 42. SML3234. Available to order from Sigma-Aldrich. SML3234. GSK778 hydrochloride hydrochloride is a potent and selective BD1 bromodomain inhibitor of the BET proteins, with IC50s of 75 nM (BRD2 BD1), 41 nM (BRD3 BD1), 41 nM (BRD4 BD1), and 143 nM (BRDT BD1), respectively. 7 GSK046 (BD2) pIC50 = 7. HK EN. Products are for research use only. A concentration of 1-2 µM of I-BET151, GSK778, GSK789, or GSK046 was used for cell culture treatments as recommended by our collaborators at GlaxoSmithKline (54–56). Herein,. Herein, GSK778 and GSK046 are referred to as iBET-BD1 and iBET-BD2, respectively. The calculations of the energy contributions of individual residues demonstrate that residues corresponding to (BD1, BD2) generate significant energy difference in binding of SG3-179, GSK778, and. 125 nM (MV-4−11 cells) ≤. 9. ≥98% (HPLC) All Photos (1)GSK778 (iBET-BD1) is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. WGK. Visit ChemicalBook To find more GSK484(1652591-81-5) information like chemical properties,Structure,melting point,boiling point,density,molecular formula,molecular weight, physical properties,toxicity information,customs codes. MR EN. Recently, inhibitors were developed that selectively target the first (BD1) and second (BD2) bromodomain of the BET proteins (iBET-BD1 [GSK778] and iBET-BD2 [GSK046]). Available to order from Sigma-Aldrich. 6147. GSK778 Hydrochloride. While GSK789 was less selective (TAF1-BD2 K d = 50 nM and TAF1L-BD2 K d = 398 nM), it. (a) Phylogenetic tree of bromodomains, with available chemical probes noted; the BET subfamily and the divergence of its first and second bromodomains, BD1 and BD2, are highlighted (adapted from chromohub. 65 In turn, pan-BD2 inhibitors (which have higher inhibitory activity for BD2 than BD1 of BET family members) are. 1 μg/mL, which we determined was the equivalent of 1000 units/mL (U/mL) via in-house. 2 (LPS-PBMC assay) <10. ≥98% (HPLC)GSK778 Hydrochloride is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. $21. Available to order from Sigma-Aldrich. GSK778 phenocopies the effects of pan-BET inhibitors in cancer models. WGK 3. gov means it’s official. FRAP, BAZ2B: 1000 3:. GSK778 phenocopied the effects of pan-BET inhibitors in cancer models. Safety Information. All Photos (1) SML3234. G-Protein-coupled Receptor Ligands. Fig. Handling should only be performed by personnel trained and familiar with handling of potent active pharmaceutical ingredients. Many reports have shown that pan BETis, such as JQ1 and iBET762, exhibited no selectivity between BD1 and BD2, but BD1-selective (GSK778) or BD2-selective (GSK046 and ABBV-744) BETis showed. Applications Products Services Documents Support. Drugs that inhibit both bromodomains equally have shown efficacy in certain malignant and inflammatory conditions. Comparison of the binding modes of CDD-956 with BD1, CDD-1302 with BRDT-BD2 , and iBET-BD1 (GSK778) with BRD4-BD1 (Fig. GSK778 Hydrochloride. GSK778 Hydrochloride is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. , 1999). Available to order from Sigma-Aldrich. Resolution:A concentration of 1-2 µM of I-BET151, GSK778, GSK789, or GSK046 was used for cell culture treatments as recommended by our collaborators at GlaxoSmithKline (54–56). SML3234. GSK778, also known as iBET-BD1, is a potent and selective inhibitor of bromodomain (BRD) BD1, with IC50s of 75 nM (BRD2 BD1). DC42300: GSK620:manuscript, GSK778 and GSK046 are termed iBETBD1 and - iBET-BD2 respectively. 53 reported the development route of iBET-BD1 from a pan-BET imidazoquinolinone-based inhibitor with a slight BD1-bias, iBET151. Available to order from Sigma-Aldrich. Available to order from Sigma-Aldrich. Copy Link. 6SWN, 6SWO, 6SWP, 6SWQ. SML3234. SML3234. 65 ABBV-744 shows potent anti-proliferative effects against. COO/ COA. - Mechanism of Action & Protocol. GSK778 (iBET-BD1) is a strong BD1 bromodomain inhibitor of the BET proteins, with IC50 value of 75 nM for BRD2 BD1, 41 nM for BRD3 BD1, 41 nM for BRD4 BD1, and 143 nM for BRDT BD1. , 2019). The authors found that in mouse models of various cancers, BD1 inhibition is reminiscent of pan-BET inhibi-tion. Available to order from Sigma-Aldrich. GSK778 (iBET-BD1) potently inhibits numerous cancer cells proliferation, inducing cell cycle arrest and apoptosis. BET proteins are linked to cancer progression. 1. 3; Cell proliferation assay with the AML cell line MV-4−11 that has a MLL-AF4 rearrangement (3 days): growth inhibition with pIC50 = 7. (A) Schematic of the BET Bromodomain proteins and chemical structures. GSK778 Hydrochloride ≥98% (HPLC); Synonyms: 4-{2-(Methoxymethyl)-1-[(R)-1-phenylethyl]-8-[(S)-pyrrolidin-3-ylmethoxy]-1H-imidazo[4,5-c]quinolin-7-yl}-3,5. All Photos (1) SML3234. SML3234. GSK778 phenotyping the role of pan-BET inhibitors in cancer models. from publication: Fast and Accurate. 2451862-42-1 GSK778 is a potent and selective inhibitor of BD1 bromodomain such as BRD2 BD1 (IC50s = 75 nM), BRD3 BD1 (IC50s = 41 nM), BRD4 BD1 (IC50s = 41 nM), and BRDT BD1 (IC50s = 143 nM). GSK778 (iBET-BD1) is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. Pan-BD1 inhibitors (which have higher inhibitory activity for BD1 than BD2 of BET proteins) are comparable to pan-BD inhibitors, such as MS436, 59 Olinone, 60 MS402, 61 3U, 62 GSK778, 19 ZL0516. 15 Gilan et al. GSK778 (iBET-BD1) potently inhibits numerous cancer cells proliferation, inducing cell cycle arrest and apoptosis. Preis und Verfügbarkeit anzeigen. Chemical probes are cell-active, selective, highly validated research tools that can be used to decipher the biology of their target.