(C) X-ray crystal structure of I-BET151 in. They also report the development of GSK620, an orally bioavailable BD2-selective inhibitor, and GSK778 (iBET-BD1), a. All Photos (1) SML3234. , 2010), BD1-specific GSK778 and BD2-specific ABBV-774 and GSK046 (Faivre et al. 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). 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). All Photos (1) SML3234. Email. 2. The two tandem bromodomains of the BET proteins enable chromatin binding to facilitate transcription. In contrast to other reported domain-selective molecules, these compounds showed little binding to bromodomains. GSK778 Hydrochloride is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. BRD4 inhibitors effectively penetrate the blood-brain barrier and target glioma tumor tissues but have little effect on normal brain tissues. to produce antitumor effects in vivo. 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. As epigenetic readers, bromodomain and extra-terminal domain (BET) family proteins bind to acetylated-lysine residues in histones and recruit protein complexes to promote transcription initiation and elongation. Forodesine hydrochloride ≥98% (HPLC); Synonyms: 7-[(2S,3S,4R,5R)-3,4-Dihydroxy-5-(hydroxymethyl)-2-pyrrolidinyl]-3,5-dihydro-4H-pyrrolo[3,2-d]pyrimidin-4-one, hydrochloride salt,BCX-1777 HCl,ImmH HCl,Immucillin-H HCl; find Sigma-Aldrich-SML3378 MSDS, related peer-reviewed papers, technical documents, similar products & more at Sigma-Aldrich We would like to show you a description here but the site won’t allow us. GSK778 Hydrochloride. Applications Products Services Documents Support. Safety Information. No; GlaxoSmithKlineBy surface plasmon resonance binding assay, GSK778 is > 130-fold selective for BD1, whereas GSK046 is > 300-fold selective for BD2 . 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. GSK778 phenocopies the. GSK778 Hydrochloride is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. , 2021). E-newsletter Get updates ,discounts and special offers. R3653. Their affinities for the individual bromodomains of the BET family were initially determined by TR-FRET (Fig. 8300 Cypress Creek Parkway, Suite 450 Houston. 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. Europe PMC is an archive of life sciences journal literature. 9. 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. rednibar) and I. SML3234. Copy Link. 3. (A) Schematic of the BET Bromodomain proteins and chemical structures. Description: GSK778, also known as iBET-BD1, is a potent and selective inhibitor of bromodomain (BRD) BD1, with IC50s of 75 nM (BRD2 BD1). 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. Storage Class Code. Copy Link. GSK778. Find (s)-1-phenylethyl (r)-acetoxyphenylacetate and related products for scientific research at MilliporeSigmaI-BET151 (GSK1210151A), iBET-BD1 (GSK778) and iBET-BD2 (GSK046) were provided by GlaxoSmithKline plc (GSK, London, UK). All Photos (1) SML3234. PubMed Abstract: The two tandem bromodomains of the BET (bromodomain and extraterminal domain) proteins enable chromatin binding to facilitate transcription. We would like to show you a description here but the site won’t allow us. WGK 3. 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. Storage Class Code. 1 in RR-multiple myeloma CC-94280 HIGHLIGHTS FROM DRUG DISCOVERY ARTICLES PUBLISHED ONLINE | MAR. GSK778 (iBET-BD1) potently inhibits numerous cancer cells proliferation, inducing cell cycle arrest and apoptosis. Drugs that inhibit both bromodomains equally have shown efficacy in certain malignant and inflammatory conditions. 13 The pyrrolidinyl group interacts with a nonconserved Asp on D1s (His on D2s) via a water-bridged hydrogen bond (Figure 1A, ,B B). 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). The mammalian bromodomain and extra-terminal domain (BET) family of proteins consists of four conserved members (Brd2, Brd3, Brd4, and Brdt) that regulate numerous cancer-related and immunity-associated genes. GSK778 (iBET-BD1) is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. SML3168. ≥98% (HPLC)We used the BD1-selective small molecule inhibitor GSK778, which largely phenocopies pan-BET inhibitors, as well as the BD2-selective inhibitor GSK046, which has more limited effects on steady. CAS#: 2451862-42-1. 77 The basic structure of BET proteins is comprised of. AA Blocks. GSK778 reduces the production of anti-keyhole limpet. described the development of GSK778 (iBET-BD1) and GSK046 (iBET-BD2), the first highly selective small-molecule inhibitors of BET-BD1 and BET-BD2, respectively . *. Cell proliferation outcomes in naïve CD4+ T cell counts following 6 days of culture, for each of the two genotypes under the four treatment conditions (i. Email. +86-21-51987688 Crystal structure of GSK778 complexed with BRD4-BD1 (Fig. GSK778 is a potent and selective inhibitor of bromodomain (BRD) BD1, with IC50s of 75 nM (BRD2 BD1). 12:01PM IST Vir Savarkar (Port Blair) - IXZ. S1F, and table S1). SML3234. Figure 5. Products are for research use only. This approachGSK778 (iBET-BD1) is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. e. 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). Data and materials availability: I-BET151, GSK778, GSK046, and GSK620 are available from R. Available to order from Sigma-Aldrich. SML3234. S9684: GSK046Visit ChemicalBook To find more GSK778(2451862-42-1) information like chemical properties,Structure,melting point,boiling point,density,molecular formula,molecular weight, physical properties,toxicity information,customs codes. HK EN. Copy Link. 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. Recombinant IL-1β (Peprotech, Cranbury, NJ) was reconstituted RPMI at 0. Drug Formulation: This drug may be formulated in DMSO. View and buy high purity iBET-BD1 | GSK778 from AOBIOUS, the leading supplier of life science reagents. GSK778 Hydrochloride. Safety Information. 511. On the basis of sequence homology, BCPs are classified into eight different subgroups (families). Applications Products Services Documents Support. 1. Comparison of the binding modes of CDD-956 with BD1, CDD-1302 with BRDT-BD2 , and iBET-BD1 (GSK778) with BRD4-BD1 (Fig. 09-Sep-2023. Applications Products Services Documents Support. Storage Class Code. You can also browse global suppliers,vendor,prices,Price,manufacturers of GSK484(1652591-81-5). 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. SML3234. Europe PMC is an archive of life sciences journal literature. Copy Link. 65 ABBV-744 shows potent anti-proliferative effects against. R (moc. iBET-BD1 phenocopies the effects of pan-BET inhibitors in cancer models, whereas iBET-BD2 is predominantly effective in. Copy Link. Membranes were blocked with 5% milk in Tris-buffered saline (TBS) with 0. Applications Products Services Documents Support. selective (GSK778) or BD2-selective (GSK046 and ABBV-744) BETis showed signicant IC 50 value dierences between BD1 and BD2 2,9,22,23. Description: GSK778, also known as iBET-BD1, is a potent and selective inhibitor of bromodomain (BRD) BD1, with IC50s of 75 nM (BRD2 BD1). GSK778 (iBET-BD1) is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. orgGSK778 Hydrochloride is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. S1F, and table S1). WGK. GSK778 Hydrochloride. GB EN. 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 was found as a BD1 selective inhibitor with 130 times higher affinity for BD1 than BD2 5. T9703 CAS 2451862-42-1. KR EN. WGK 3. GSK778 phenocopies the effects of pan-BET inhibitors in cancer models [1]. The authors report the development of GSK046 (iBET-BD2), a potent BD2-selective inhibitor with >1000-fold selectivity over BD1. Drugs that inhibit both bromodomains equally have shown efficacy in certain malignant and inflammatory conditions. Their affinities for the individual bromodomains of the BET family were initially determined by TR-FRET (Fig. GSK778 Hydrochloride. 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. Federal government websites often end in . 0; BRD4 (BD2) pKd = 5. Copy Link. The imidazoquinolinone 8-position of iBET151 was identified as orienting towards the. Cell lysates were separated by SDS-PAGE on [email protected] μg/mL, which we determined was the equivalent of 1000 units/mL (U/mL) via in-house. DC42300: GSK620:manuscript, GSK778 and GSK046 are termed iBETBD1 and - iBET-BD2 respectively. nM, SPR BRD4 (BD1): pKd= 8. BD1-selective tool (GSK778) BD2-selective tool (GSK046) BRD4 BD1 IC 50: >50000 nM BRD4 BD2 IC 50: 50 nM BRD4 BD1 IC50: 40 nM BRD4 BD2 IC50: 6300 nM Reduced off-target binding Ph. Open in a separate window. 1iBET-BD1 (GSK778) Following the initial report of the biological activity of iBET-BD1 and iBET-BD2, 19 Wellaway et al. MH EN. All Photos (1) Documents. Not for human use. 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. Preis und Verfügbarkeit anzeigen. Hazard Description: Toxic. ( B ) Compound binding to the. Primary Citation of Related Structures: 6SWN, 6SWO, 6SWP, 6SWQ. 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. 4. 999. Storage Class Code. TW EN. D5782. All Photos (1) Documents. Molecular Weight: 511. 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. Copy Link. EG EN. 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. 3; Cell. COO/ COA. Email. ABBV-744 is highly selective for BD2 of BRD2, BRD3 and BRD4, 64 exhibiting several hundred-fold higher affinity for the BD2 over BD1. 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) Documents. GSK778 phenocopied the effects of pan-BET inhibitors in cancer models. ≥98% (HPLC)GSK778 Hydrochloride is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. GSK778 (iBET-BD1) potently inhibits numerous cancer cells proliferation, inducing cell cycle arrest and apoptosis. Of these, only ABBV-744 and two molecules described within the article, GSK778 (iBET-BD1) and GSK046 (iBET-BD2) showed appreciable selectivity. 1A). 5 mg/dL, except in individuals with Gilbert's syndrome. The two tandem bromodomains of the BET. GSK778 Hydrochloride is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. 00. Another report showed that BD2-selective BET family inhibitors exhibited good efficacies in treating prostate cancer 22. They are useful assets for example, in phenotypic assays, or as a starting point for medicinal chemistry campaigns. 2h 04m. MS40229, and GSK77830. GSK778 Hydrochloride is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. Download scientific diagram | Inhibition of CDK6 confers drug sensitivity to AKTi. GSK778 Hydrochloride. We do not sell to patients. 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. All products from TargetMol are for Research Use. Developing BDII selective compounds was far more challenging, and only a handful of BDII selective inhibitors have been developed to date (Figure 1). GSK778 (iBET-BD1) [GSK reference 1, 5] is an analogue of I-BET151 [68] with good potency against BET BD1s (IC 50 s ≈ 40–75 nM) and similar selectivity to LT052 between the BDs of BRD4 (110-fold -to 140-fold depending on assay format), but this selectivity is slightly lower for BRD2 and BRD3 (30–65-fold). COO/ COA. 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. Fig. We do not sell to patients. ≥98% (HPLC)We would like to show you a description here but the site won’t allow us. GSK778 Hydrochloride. 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. 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. Applications Products Services Documents Support. A320. Hazard Description: Toxic. All Photos (1) Documents. Available to order from Sigma-Aldrich. To date, 61 bromodomains have been identified in 46 diverse proteins in human cells (Filippakopoulos et al. S9683 Synonyms: iBET-BD1. The oldest compound, RVX-208 based on a quinazolinone chemical core, exhibited a selectivity of 20-fold with K D values of 4100 nMComprar GSK778 hydrochloride na CymitQuimica a partir de 187,0 €I-BET151 (GSK1210151A), iBET-BD1 (GSK778) and iBET-BD2 (GSK046) were provided by GlaxoSmithKline plc (GSK, London, UK). 00. BD1 selective inhibitors, such as GSK778, MS-436, Olinone, and BI-2536, as well as the BD2 selective inhibitors RVX-208, RVX-297, GSK046, and ABBV-744 have been produced. GSK778 Hydrochloride is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. WGK 3. Forodesine hydrochloride ≥98% (HPLC); Synonyms: 7-[(2S,3S,4R,5R)-3,4-Dihydroxy-5-(hydroxymethyl)-2-pyrrolidinyl]-3,5-dihydro-4H-pyrrolo[3,2-d]pyrimidin-4-one, hydrochloride salt,BCX-1777 HCl,ImmH HCl,Immucillin-H HCl; find Sigma-Aldrich-SML3378 MSDS, related peer-reviewed papers, technical documents, similar products & more at Sigma. Handling should only be performed by personnel trained and familiar with handling of potent active pharmaceutical ingredients. SML3234. Buy Epigenetic Reader Domain inhibitor GSK778 (iBET-BD1) from AbMole BioScience. Miransertib is a highly selective, orally active, pan-Akt inhibitor. Coordinates and structure factors have been deposited in the Protein Data Bank (PDB) with identification code 6SWN, 6SWO, 6SWP and 6SWQ. ≥98% (HPLC)Herein, GSK778 and GSK046 are referred to as iBET-BD1 and iBET-BD2, respectively. Email. All Photos (1) Documents. 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 (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 phenocopies the. RVX-297 is a 4-quinazolinone derivative related to RVX-208 with an alkylpyrrolidine side chain off the di-methyl substituted phenyl ring (Fig. GSK778 Hydrochloride. 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. Applications Products Services Documents Support. P (moc. ([email protected]) and I. Les inhibiteurs spécifiques du. 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. +86-21-51987688Crystal structure of GSK778 complexed with BRD4-BD1 (Fig. COO/ COA. All Photos (1) SML3234. COO/ COA. 9. Nevertheless, it was more efficacious in a broad range of cancers and inflammatory pathologies [25]. 2451862-42-1: Formula: C 30 H 33 N 5 O 3: Formula Wt. JP EN. Louis Gilman July 17, 2023. But, how does GSK778 work on the target? Let’s discuss it in detail. GSK778 Hydrochloride is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. 2451862-42-1. 2451862-42-1. ≥98% (HPLC)They also report the development of GSK620, an orally bioavailable BD2-selective inhibitor, and GSK778 (iBET-BD1), a BD1-selective inhibitor (see the figure). Available to order from Sigma-Aldrich. 1 Among these, bromodomain and extraterminal (BET) proteins constitute a unique group with four family members, bromodomain-containing protein 4 (BRD4), BRD3, BRD2, and. Email. 2 (LPS-PBMC assay) <10. 3 Details of the supplier of the safety data sheet; Company: Abmole Bioscience Inc. * Please kindly note that our products are not to be used for therapeutic purposes and cannot be sold to patients. 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. ≥98% (HPLC)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. iBET-BD1 dihydrochloride . 1. Copy Link. ≥98% (HPLC) All Photos (1)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. When bound to. Of these, only ABBV-744 and two molecules described within the article, GSK778 (iBET-BD1) and GSK046 (iBET-BD2) showed appreciable selectivity. 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. 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. Email. Available to order from Sigma-Aldrich. Lymphoma Non. amni) under a material transfer agreement with GSK. SML3234. Selectivity profile of I-BET151, iBET-BD1 (GSK778), and iBET-BD2 (GSK046). Email. Copy Link. Copy Link. PL EN. Applications Products Services Documents Support. GSK778 Hydrochloride is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. DNA/RNA Synthesis Inhibitor/Blocker. . K. Storage Class Code. CAS Number: 2451862-42-1. MedKoo CAT#: 408120. , 2019). GSK778: 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. Available to order from Sigma-Aldrich. COO/ COA. However, many compounds reported in the literature and routinely studied in biomedical research lack the potency and selectivity. 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. Catalog No. CTB ( Cholera Toxin B subunit ) Catalog No. COO/ COA. GSK778 phenocopies the effects of pan-BET inhibitors in cancer models. The two. HR EN. BD1 selective inhibitors, such as GSK778, MS-436, Olinone, and BI-2536, as well as the BD2 selective inhibitors RVX-208, RVX-297, GSK046, and ABBV-744 have been produced. 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. WGK 3. For research use only. All Photos (1) Documents. Copy Link. GSK778 phenocopies the. ≥98% (HPLC)GSK778 Hydrochloride is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. CA EN. Hazard identification. Herein,. 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]. Guanidine hydrochloride; Useful for denaturing proteins and solubilization of inclusion bodies. M28843 CAS No. COO/ COA. 3. CAS No. 1. In contrast to pan-BET proteins inhibitors, these selective BET proteins inhibitors of BD1 or BD2 are characterizedCas No. Glatiramer acetate generates anti-inflammatory Th2 cells, which produce neurotrophic factors. GSK778 phenocopies the effects of pan-BET inhibitors in cancer models. 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. R. GSK778 Hydrochloride is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. BRD4. Fig. WGK 3. 5 ± 0. Shelf Life: >3 years if stored properly. K. Theoretical Analysis Hodoodo Cat#: H408120 Name: GSK778 CAS#: 2451862-42-1By surface plasmon resonance binding assay, GSK778 is > 130-fold selective for BD1, whereas GSK046 is > 300-fold selective for BD2 [26]. Selectivity profile of I-BET151, iBET-BD1 (GSK778) and iBET-BD2 (GSK046). GSK046 (iBET-BD2) es un inhibidor de bromodominio BD2 potente, selectivo y oralmente activo de las proteÍnas BET, con IC50 de 264 nM (BRD2 BD2), 98 nM (BRD3 BD2), 49 nM (BRD4 BD2) y 214 nM (BRDT BD2), respectivamente. MS EN. Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months). Instead, a unique effect of BD2-selective antagonism was revealed with GSK046 affecting the induction of gene expression more so than the expression of steady-state genes, in contrast to GSK778 . Molecular Weight: 511. 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. SML3234. 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. Where indicated, 1 μm GSK778 or GSK046 or carrier (DMSO) were added at the same time as LPS. , 2016). Compounds GSK778 (5) and GSK046 (6) are recently reported BET BD1-selective and BET BD2-selective small molecule inhibitors with >130-fold and >300-fold selectivity over the other corresponding bromodomains, respectively, as determined by surface plasmon resonance (SPR) assays. Safety Information. GSK778: CAS Registry Number: 2451862-42-1: Molecular Weight: 511. 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. Preis und Verfügbarkeit anzeigen. We do not sell to patients. PK EN. Email. GSK789 was derived from a series of naphthyridone ATAD2 inhibitors. GSK778 hydrochloride | C30H34ClN5O3 | CID 168013350 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological. Shelf Life: >2 years if stored properly. 65 In turn, pan-BD2 inhibitors (which have higher inhibitory activity for BD2 than BD1 of BET family members) are. 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. Applications Products Services Documents Support. ( A ) Schematic of the BET bromodomain proteins and chemical structures. Selectivity profile of I-BET151, iBET-BD1 (GSK778) and iBET-BD2 (GSK046). Comprar GSK778 hydrochloride na CymitQuimica a partir de 181,0 € Iniciar Sessão Criar uma conta. Available to order from Sigma-Aldrich. 1 μg/mL, which we determined was the equivalent of 1000 units/mL (U/mL) via in-house Griess assay. AU EN. Email. Open in a separate window. GSK778 hydrochloride hydrochloride phenocopies the effects of pan-BET inhibitors in cancer models[1]. GSK778 phenocopies the effects of pan-BET inhibitors in cancer models[1]. GSK778 (iBET-BD1) potently inhibits numerous cancer cells proliferation, inducing cell cycle arrest and apoptosis. 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. They are epigenetic readers of histone acetylation with broad specificity. ≥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. Storage Class Code. IL EN. GSK778 (iBET-BD1) potently inhibits numerous cancer cells proliferation, inducing cell cycle arrest and apoptosis. - Mechanism of Action & Protocol. Here, two unexpected findings are reported: (1) SynGRs bearing pan-BET or BD2-selective ligands license transcription at the FXN locus, whereas those bearing BD1-selective ligands do not, and (2) rather than being neutral or inhibitory, an untethered BD1-selective ligand (GSK778) substantively enhances the activity of all active SynGRs. Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years). from publication: Fast and Accurate. Drugs that inhibit both bromodomains equally have shown efficacy in certain malignant and inflammatory conditions. SML3234. 6swn: n-terminal bromodomain of human brd4 with ibet-bd1 (gsk778)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. $79. GSK778 (iBET-BD1) is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. Instead, a unique effect of BD2-selective antagonism was revealed with GSK046, affecting the induction of gene expression more so than the expression of steady-state genes, in contrast to GSK778 [28]. Applications Products Services Documents Support. 6swo: c-terminal bromodomain of human brd2 with ibet-bd1 (gsk778)BRD3. 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. showed that BD(1)-specific GSK778 phenocopied the effects of pan-BET BRD inhibitors, while GSK046 and its orally bioavailable GSK620 derivative had minimal impact on cell viability while impairing the induction, but not the maintenance, of transcriptional programs [133]. WGK. ≥98% (HPLC)GSK778 Hydrochloride is a potent and highly selective inhibitor of bromodomain BD1 of BRD2, BDR3, BRD4, BRDT. COO/ COA. This was explained by displacement of BET proteins from promoter and enhancer regions that control MYC expression, suggest-ing that BD1 anchors BET. SML3234. Catalog Number: AA01KEG7. , 2020). All Photos (1) Documents. Storage Class Code. 5% gels (100 V, 90 min) and transferred to nitrocellulose membranes (90 V, 90 min). COO/ COA. 2451862-42-1 related products. Copy Link. Their affinities for the individual bromodomains of the BET family were initially determined by TR-FRET (Fig. BRD3 (BD1) pIC. 1A and GSK046/GSK620) [13,14] and a pan-D1 inhibitor, GSK778 were disclosed this year. All Photos (1) Documents. Available to order from Sigma-Aldrich. 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. BD1 selective inhibitors, such as GSK778, MS-436, Olinone, and BI-2536, as well as the BD2 selective inhibitors RVX-208, RVX-297, GSK046, and ABBV-744 have been produced. Catalog No. Email. PubMed Abstract: The two tandem bromodomains of the BET (bromodomain and extraterminal domain) proteins enable chromatin binding to facilitate transcription. Catalog Number: AA01KEG7. 61 bulk manufacturing, sourcing and procurement.