Synonym
I-CBP112; I-CBP-112; I-CBP 112.
IUPAC/Chemical Name
(S)-1-(7-(3,4-dimethoxyphenyl)-9-((1-methylpiperidin-3-yl)methoxy)-2,3-dihydrobenzo[f][1,4]oxazepin-4(5H)-yl)propan-1-one
InChi Key
YKNAKDFZAWQEEO-IBGZPJMESA-N
InChi Code
InChI=1S/C27H36N2O5/c1-5-26(30)29-11-12-33-27-22(17-29)13-21(20-8-9-23(31-3)24(14-20)32-4)15-25(27)34-18-19-7-6-10-28(2)16-19/h8-9,13-15,19H,5-7,10-12,16-18H2,1-4H3/t19-/m0/s1
SMILES Code
CCC(N1CCOC2=C(OC[C@@H]3CN(C)CCC3)C=C(C4=CC=C(OC)C(OC)=C4)C=C2C1)=O
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
More Info
CREBBP (CBP) and EP300 are general transcriptional co-activators, which 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 plays and essential role in neuronal plasticity/ memory formation, hematopoiesis and energy homeostasis as demonstrated in a variety of mouse models. By acetylation of non-histone proteins CREBBP can have a positive or negative effect on transcriptional regulation affecting protein- protein interactions, protein-DNA interactions, nuclear retention or protein half-life.
Mutations of CREBBP and EP300 lead to Rubinstein-Taybi syndrome (RTS), characterised by growth retardation, facial abnormalities, organ abnormalities, mental retardation and proneness to tumors. Chromosomal translocations of CREBBP or EP300 with MOZ, MLL have been observed in acute myeloid leukemia. CREBBP has also been associated with Amyotrophic lateral sclerosis (ALS), Lou Gherig’s disease, a neurodegenerative disease with progressive degeneration of motor neurons in the brain and spinal cord, Alzheimer's disease and polyglutamine diseases such as Spinal and Bulbar Muscular Atrophy and Huntington’s disease
(http://www.thesgc.org/chemical-probes/I-CBP112)
Biological target:
I-CBP112 is a specific and potent acetyl-lysine competitive protein-protein interaction inhibitor, that inhibits the CBP/p300 bromodomains, enhances acetylation by p300.
In vitro activity:
The inhibition of this demethylase in the presence of I-CBP112 prevented the repression of ABCC1 and ABCC10 and, to a considerable extent, cancer cells' sensitization to drugs. In conclusion, the CBP/p300 bromodomain inhibitor I-CBP112 can be considered as a potent anti-multidrug-resistance agent, capable of repressing key ABC transporters responsible for drug efflux in various cancer types.
Reference: Cancers (Basel). 2021 Sep 14;13(18):4614. https://pubmed.ncbi.nlm.nih.gov/34572840/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
63.0 |
134.44 |
| Ethanol |
94.0 |
200.60 |
| Water |
94.0 |
200.60 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
468.59
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. Strachowska M, Gronkowska K, Michlewska S, Robaszkiewicz A. CBP/p300 Bromodomain Inhibitor-I-CBP112 Declines Transcription of the Key ABC Transporters and Sensitizes Cancer Cells to Chemotherapy Drugs. Cancers (Basel). 2021 Sep 14;13(18):4614. doi: 10.3390/cancers13184614. PMID: 34572840; PMCID: PMC8467251.
2. Zucconi BE, Makofske JL, Meyers DJ, Hwang Y, Wu M, Kuroda MI, Cole PA. Combination Targeting of the Bromodomain and Acetyltransferase Active Site of p300/CBP. Biochemistry. 2019 Apr 23;58(16):2133-2143. doi: 10.1021/acs.biochem.9b00160. Epub 2019 Apr 11. PMID: 30924641; PMCID: PMC6948846.
In vitro protocol:
1. Strachowska M, Gronkowska K, Michlewska S, Robaszkiewicz A. CBP/p300 Bromodomain Inhibitor-I-CBP112 Declines Transcription of the Key ABC Transporters and Sensitizes Cancer Cells to Chemotherapy Drugs. Cancers (Basel). 2021 Sep 14;13(18):4614. doi: 10.3390/cancers13184614. PMID: 34572840; PMCID: PMC8467251.
2. Zucconi BE, Makofske JL, Meyers DJ, Hwang Y, Wu M, Kuroda MI, Cole PA. Combination Targeting of the Bromodomain and Acetyltransferase Active Site of p300/CBP. Biochemistry. 2019 Apr 23;58(16):2133-2143. doi: 10.1021/acs.biochem.9b00160. Epub 2019 Apr 11. PMID: 30924641; PMCID: PMC6948846.
1: Picaud S, Fedorov O, Thanasopoulou A, Leonards K, Jones K, Meier J, Olzscha H,
Monteiro O, Martin S, Philpott M, Tumber A, Filippakopoulos P, Yapp C, Wells C,
Che KH, Bannister A, Robson S, Kumar U, Parr N, Lee K, Lugo D, Jeffrey P, Taylor
S, Vecellio ML, Bountra C, Brennan PE, O'Mahony A, Velichko S, Müller S, Hay D,
Daniels DL, Urh M, La Thangue NB, Kouzarides T, Prinjha R, Schwaller J, Knapp S.
Generation of a Selective Small Molecule Inhibitor of the CBP/p300 Bromodomain
for Leukemia Therapy. Cancer Res. 2015 Dec 1;75(23):5106-19. doi:
10.1158/0008-5472.CAN-15-0236. Epub 2015 Nov 9. PubMed PMID: 26552700.
