WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406442
Description: SGC-CBP30 is a potent and selective inhibitor of CREBBP (CBP) and EP300; which are general transcriptional co-activators. CREBBP has also been associated with Amyotrophic Lateral Sclerosis (ALS) or Lou GehrigÂ’s disease, a neurodegenerative disease with progressive degeneration of motor neurons in the brain and spinal cord, Alzheimer's disease and poly glutamine repeat diseases such as Spinal and Bulbar Muscular Atrophy and HuntingtonÂ’s disease. (http://www.thesgc.org/chemical-probes/SGC-CBP30).
MedKoo Cat#: 406442
Chemical Formula: C28H33ClN4O3
Exact Mass: 508.22412
Molecular Weight: 509.03962
Elemental Analysis: C, 66.07; H, 6.53; Cl, 6.96; N, 11.01; O, 9.43
Synonym: SGC-CBP30; SGC-CBP 30; SGC-CBP-30.
IUPAC/Chemical Name: (S)-4-(1-(2-(3-chloro-4-methoxyphenethyl)-5-(3,5-dimethylisoxazol-4-yl)-1H-benzo[d]imidazol-1-yl)propan-2-yl)morpholine
InChi Key: GEPYBHCJBORHCE-SFHVURJKSA-N
InChi Code: InChI=1S/C28H33ClN4O3/c1-18(32-11-13-35-14-12-32)17-33-25-8-7-22(28-19(2)31-36-20(28)3)16-24(25)30-27(33)10-6-21-5-9-26(34-4)23(29)15-21/h5,7-9,15-16,18H,6,10-14,17H2,1-4H3/t18-/m0/s1
SMILES Code: C[C@H](N1CCOCC1)CN2C(CCC3=CC=C(OC)C(Cl)=C3)=NC4=CC(C5=C(C)ON=C5C)=CC=C24
Appearance: white to off-white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
|Biological target:||SGC-CBP30 is a potent and highly selective CBP/p300 bromodomain (Kds of 21 nM and 32 nM for CBP and p300, respectively) inhibitor, displaying 40-fold selectivity over the first bromodomain of BRD4 [BRD4(1)] bound.|
|In vitro activity:||In order to know whether SGC-CBP30 treatment has an effect on IL6 autocrine secretion in XG1LenRes cells, we measured IL6 in the culture media of XG1LenRes in the absence and presence of drug treatment. As shown in Fig,6c, SGC-CBP30 treatment reduced IL6 autocrine production from XG1LenRes in either the absence or presence of lenalidomide. Accordingly, STAT3 activation was inhibited by SGC-CBP30 treatment (Fig.6b). Finally, we demonstrated that SGC-CBP30 also increased the sensitivity to lenalidomide in three IMiD-sensitive HMCLs (supplementary Figure 9D–F). SGC-CBP30 treatment could change the chromatin structure in the IRF4 and MYC regulatory regions or regulate other genes in IMiDs-mediated activity, therefore inducing increased sensitivity to IMiD-induced signals (such as downregulation of IKZF1/IKZF3). Reference: Blood Cancer J. 2019 Feb; 9(2): 19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6370766/|
|In vivo activity:||Lung injury in septic mice was characterized by alveolar septal thickening, extensive edema, massive infiltration of inflammatory cells, and alveolar congestion/collapse. In lungs from the SGC-CBP30-8 h therapy group, LPS- or CLP-induced histopathological damage and accumulation of inflammatory cells were attenuated (Figures 2A, B, first-line). Semi-quantitative assessment of lung histology revealed that administration of SGC-CBP30 at 8 h following LPS or CLP significantly decreased tissue injury in the lung, similar to the positive control DEX-0.5 h. In the SGC-CBP30-8 h treatment group, infiltrated inflammatory cells were significantly reduced and liver architecture was significantly improved (Figures 2A, B, third-line). As shown in Semi-quantitative statistics, administration of SGC-CBP30 at 8 h or DEX at 0.5 h after septic modeling markedly reduced liver injury scores. It is clear that the delayed SGC-CBP30 administration at 8 h significantly attenuated the histopathological deterioration and inflammatory cell infiltration in renal tissues. Together, these results demonstrate that selective CBP bromodomain inhibitors such as SGC-CBP30 may be effective not only to suppress inflammatory response in organs, but also to ameliorate organ injury caused by LPS-induced endotoxemia and CLP-induced sepsis. Reference: Front Immunol. 2020; 11: 625542. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884462/|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
The following data is based on the product molecular weight 509.03962 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
|Formulation protocol:||1. Zhu YX, Shi CX, Bruins LA, Wang X, Riggs DL, Porter B, Ahmann JM, de Campos CB, Braggio E, Bergsagel PL, Stewart AK. Identification of lenalidomide resistance pathways in myeloma and targeted resensitization using cereblon replacement, inhibition of STAT3 or targeting of IRF4. Blood Cancer J. 2019 Feb 11;9(2):19. doi: 10.1038/s41408-019-0173-0. PMID: 30741931; PMCID: PMC6370766. 2. Sun J, Zhang W, Tan Z, Zheng C, Tang Y, Ke X, Zhang Y, Liu Y, Li P, Hu Q, Wang H, Mao P, Zheng Z. Zika virus promotes CCN1 expression via the CaMKIIα-CREB pathway in astrocytes. Virulence. 2020 Dec;11(1):113-131. doi: 10.1080/21505594.2020.1715189. PMID: 31957543; PMCID: PMC6984649. 3. Bi X, Jiang B, Zhou J, Fan X, Yan X, Liang J, Luo L, Yin Z. CBP Bromodomain Inhibition Rescues Mice From Lethal Sepsis Through Blocking HMGB1-Mediated Inflammatory Responses. Front Immunol. 2021 Feb 2;11:625542. doi: 10.3389/fimmu.2020.625542. PMID: 33603756; PMCID: PMC7884462.|
|In vitro protocol:||1. Zhu YX, Shi CX, Bruins LA, Wang X, Riggs DL, Porter B, Ahmann JM, de Campos CB, Braggio E, Bergsagel PL, Stewart AK. Identification of lenalidomide resistance pathways in myeloma and targeted resensitization using cereblon replacement, inhibition of STAT3 or targeting of IRF4. Blood Cancer J. 2019 Feb 11;9(2):19. doi: 10.1038/s41408-019-0173-0. PMID: 30741931; PMCID: PMC6370766. 2. Sun J, Zhang W, Tan Z, Zheng C, Tang Y, Ke X, Zhang Y, Liu Y, Li P, Hu Q, Wang H, Mao P, Zheng Z. Zika virus promotes CCN1 expression via the CaMKIIα-CREB pathway in astrocytes. Virulence. 2020 Dec;11(1):113-131. doi: 10.1080/21505594.2020.1715189. PMID: 31957543; PMCID: PMC6984649.|
|In vivo protocol:||1. Bi X, Jiang B, Zhou J, Fan X, Yan X, Liang J, Luo L, Yin Z. CBP Bromodomain Inhibition Rescues Mice From Lethal Sepsis Through Blocking HMGB1-Mediated Inflammatory Responses. Front Immunol. 2021 Feb 2;11:625542. doi: 10.3389/fimmu.2020.625542. PMID: 33603756; PMCID: PMC7884462.|
CREBBP (CBP) and EP300 are involved in many biological processes like maintenance of genomic stability by affecting DNA replication and DNA repair as well as cell growth, transformation and development. They also play and essential role in neuronal plasticity/ memory formation hematopoiesis and energy homeostasis as demonstrated in a variety of mouse models. They possess both acetyl-transferase enzymatic and bromodomain containing regions. Through acetylation of non-histone proteins CREBBP can have a positive or negative effect on transcriptional regulation by affecting protein- protein interactions, protein-DNA interactions, nuclear retention or protein half-life. (http://www.thesgc.org/chemical-probes/SGC-CBP30).