1613695-14-9 Usage
Description
SGC-CBP30 is a potent CBP/p300 bromodomain (BRD) inhibitor, characterized by its high affinity for the bromodomain of CREBBP/EP300 proteins. With dissociation constant (Kd) values of 21 and 32 nM for CBP and p300 BRDs respectively, SGC-CBP30 demonstrates a significant level of selectivity, being 40-fold and 250-fold selective for CBP over the first BRD of BRD4 (BRD4(1)) and BRD4(2), respectively. Additionally, it has been shown to accelerate FRAP recovery in cells at a concentration of 1 μM.
Uses
Used in Pharmaceutical Industry:
SGC-CBP30 is used as a potent CREBBP/EP300 inhibitor for the development of novel therapeutic strategies targeting the bromodomain and extraterminal (BET) proteins. Its high selectivity and potency make it a valuable compound in the research and development of drugs aimed at modulating the activity of these proteins, which are involved in various cellular processes, including gene transcription, cell cycle regulation, and inflammation.
Used in Research Applications:
In the field of academic and industrial research, SGC-CBP30 is utilized as a valuable tool compound for studying the role of CBP/p300 bromodomain proteins in various biological processes and disease pathways. Its ability to selectively inhibit these proteins can help researchers gain a better understanding of their functions and potential therapeutic applications.
Used in Drug Discovery and Development:
SGC-CBP30 is employed as a lead compound in the drug discovery and development process, particularly for the identification and optimization of novel inhibitors targeting the bromodomain and extraterminal (BET) protein family. Its high potency and selectivity make it an attractive starting point for the design and synthesis of new molecules with improved pharmacological properties and therapeutic potential.
Used in Epigenetic Regulation Studies:
In the field of epigenetics, SGC-CBP30 is used as a research tool to investigate the role of bromodomain-containing proteins in the regulation of gene expression. By inhibiting the bromodomain of CBP/p300, researchers can study the effects of this inhibition on chromatin structure, transcriptional regulation, and cellular processes influenced by these epigenetic regulators.
Used in Cancer Research:
In cancer research, SGC-CBP30 is utilized as a potential therapeutic agent for the treatment of various types of cancer. The bromodomain and extraterminal (BET) proteins, which are targeted by SGC-CBP30, have been implicated in the regulation of oncogenes and the promotion of cancer cell survival and proliferation. By inhibiting these proteins, SGC-CBP30 may offer a novel approach to disrupt cancer-related pathways and inhibit tumor growth.
Used in Inflammation and Immunology Research:
In the fields of inflammation and immunology, SGC-CBP30 is employed as a research tool to study the role of bromodomain-containing proteins in the regulation of inflammatory responses and immune cell function. The inhibition of CBP/p300 bromodomain proteins by SGC-CBP30 can provide insights into the molecular mechanisms underlying inflammation and immune regulation, potentially leading to the development of new therapeutic strategies for inflammatory and autoimmune diseases.
Biochem/physiol Actions
SGC-CBP30 is a selective inhibitor of the bromodomain-containing transcription factors CREBBP (CBP) and EP300 (IC50 = 0.021 and 0.038 μM, respectively). SGC-CBP30 has little activity against other bromodomains at concentrations up to 1 mM. For full characterization details, please visit the SGC-CBP30 probe summary on the Structural Genomics Consortium (SGC) website.To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc
Check Digit Verification of cas no
The CAS Registry Mumber 1613695-14-9 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,6,1,3,6,9 and 5 respectively; the second part has 2 digits, 1 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 1613695-14:
(9*1)+(8*6)+(7*1)+(6*3)+(5*6)+(4*9)+(3*5)+(2*1)+(1*4)=169
169 % 10 = 9
So 1613695-14-9 is a valid CAS Registry Number.
1613695-14-9Relevant articles and documents
Discovery and optimization of small-molecule ligands for the CBP/p300 bromodomains
Hay, Duncan A.,Fedorov, Oleg,Martin, Sarah,Singleton, Dean C.,Tallant, Cynthia,Wells, Christopher,Picaud, Sarah,Philpott, Martin,Monteiro, Octovia P.,Rogers, Catherine M.,Conway, Stuart J.,Rooney, Timothy P. C.,Tumber, Anthony,Yapp, Clarence,Filippakopoulos, Panagis,Bunnage, Mark E.,Müller, Susanne,Knapp, Stefan,Schofield, Christopher J.,Brennan, Paul E.
, p. 9308 - 9319 (2014/07/21)
Small-molecule inhibitors that target bromodomains outside of the bromodomain and extra-terminal (BET) sub-family are lacking. Here, we describe highly potent and selective ligands for the bromodomain module of the human lysine acetyl transferase CBP/p300, developed from a series of 5-isoxazolyl-benzimidazoles. Our starting point was a fragment hit, which was optimized into a more potent and selective lead using parallel synthesis employing Suzuki couplings, benzimidazole-forming reactions, and reductive aminations. The selectivity of the lead compound against other bromodomain family members was investigated using a thermal stability assay, which revealed some inhibition of the structurally related BET family members. To address the BET selectivity issue, X-ray crystal structures of the lead compound bound to the CREB binding protein (CBP) and the first bromodomain of BRD4 (BRD4(1)) were used to guide the design of more selective compounds. The crystal structures obtained revealed two distinct binding modes. By varying the aryl substitution pattern and developing conformationally constrained analogues, selectivity for CBP over BRD4(1) was increased. The optimized compound is highly potent (K d = 21 nM) and selective, displaying 40-fold selectivity over BRD4(1). Cellular activity was demonstrated using fluorescence recovery after photo-bleaching (FRAP) and a p53 reporter assay. The optimized compounds are cell-active and have nanomolar affinity for CBP/p300; therefore, they should be useful in studies investigating the biological roles of CBP and p300 and to validate the CBP and p300 bromodomains as therapeutic targets.