| Identification | Back Directory | [Name]
5H-Pyrazolo[4,3-c]pyridine-5-carboxamide, 3-[7-(difluoromethyl)-3,4-dihydro-6-(1-methyl-1H-pyrazol-4-yl)-1(2H)-quinolinyl]-1-[1-[15-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-5-yl]amino]-1-oxo-4,7,10,13-tetraoxapentadec-1-yl]-4-piperidinyl]-1,4,6,7-tetrahydro-N-methyl- | [CAS]
2484739-25-3 | [Synonyms]
dCBP-1
3-(7-(Difluoromethyl)-6-(1-methyl-1H-pyrazol-4-yl)-3,4-dihydroquinolin-1(2H)-yl)-1-(1-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)-3,6,9,12-tetraoxapentadecan-15-oyl)piperidin-4-yl)-N-methyl-1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxamide
5H-Pyrazolo[4,3-c]pyridine-5-carboxamide, 3-[7-(difluoromethyl)-3,4-dihydro-6-(1-methyl-1H-pyrazol-4-yl)-1(2H)-quinolinyl]-1-[1-[15-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-5-yl]amino]-1-oxo-4,7,10,13-tetraoxapentadec-1-yl]-4-piperidinyl]-1,4,6,7-tetrahydro-N-methyl- | [Molecular Formula]
C51H63F2N11O10 | [MDL Number]
MFCD34471098 | [MOL File]
2484739-25-3.mol | [Molecular Weight]
1028.11 |
| Chemical Properties | Back Directory | [density ]
1.47±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C, sealed storage, away from moisture and light | [solubility ]
DMSO : 50 mg/mL (48.63 mM; ultrasonic and warming and heat to 80°C) | [form ]
Solid | [pka]
10.80±0.40(Predicted) | [color ]
Light yellow to yellow | [InChIKey]
ILVRLRGBSSFKIE-UHFFFAOYSA-N | [SMILES]
C1N(C(NC)=O)CCC2N(C3CCN(C(=O)CCOCCOCCOCCOCCNC4C=CC5=C(C=4)C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)N=C(N3C4=C(C=C(C5=CN(C)N=C5)C(C(F)F)=C4)CCC3)C1=2 |
| Hazard Information | Back Directory | [Uses]
dCBP-1 is exceptionally potent at killing multiple myeloma cells and can abolish the enhancer that drives MYC oncogene expression. As an efficient degrader of this unique class of acetyltransferases, dCBP-1 is a useful tool alongside domain inhibitors for dissecting the mechanism by which these factors coordinate enhancer activity in normal and diseased cells.
| [Biological Activity]
dCBP-1 is a potent and selective heterobifunctional degrader of p300/CBP based on PROTAC. dCBP-1 is exceptionally potent at killing multiple myeloma cells and ablates oncogenic enhancer activity driving MYC expression[1].
dCBP-1 (10-1000 nM; 6 hours) treatment shows near-complete degradation of p300/CBP in MM1S cells. dCBP-1 is also able to induce near-complete p300/CBP degradation across other multiple myeloma cell lines tested, including MM1R, KMS-12-BM, and KMS34[1].Treatment of the human haploid cell line HAP1 for 6 h with dCBP-1 reveals almost complete loss of both CBP and p300 between 10 and 1000 nM doses. A time course analysis with 250 nM dCBP-1 revealed almost complete degradation of p300/CBP within an hour of treatment[1]. | [Synthesis]
3-(7-(difluoromethyl)-6-(1-methyl-1H-pyrazol-4-yl)-3,4-dihydroquinolin-1(2H)-yl)-1-(1-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)-3,6,9,12-tetraoxapentadecan-15-oyl)piperidin-4-yl)-N-methyl-1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxamide dCBP-1: The compound tert-butyl 3-(7-(difluoromethyl)-6-(1-methyl-1H-pyrazol-4-yl)-3,4-dihydroquinolin-1(2H)-yl)-1-(1-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)-3,6,9,12-tetraoxapentadecan-15-oyl)piperidin-4-yl)-1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxylate S18 (0.010 g, 0.01 mmol) was dissolved in 1:1 DCM: TFA (1 mL) and stirred for 30 min. The solvents were evaporated under reduced pressure, and the crude reaction mixture was dissolved in DCM (1 mL), TEA (0.1 mL), and N-methyl-1H-imidazole-1-carboximide (3.5 mg, 0.03 mmol) was added at RT and stirred overnight. Volatiles were evaporated, and the crude reaction mixture was purified by ISCO using C18 (14g) column, 0-100% MeOH/water to yield dCBP-1 (0.008 g, 80%) as a yellow oil. | [IC 50]
p300/CBP; Cereblon | [storage]
Store at -20°C, sealed storage, away from moisture and light | [References]
[1]. Raghu Vannam, et al. Targeted degradation of the enhancer lysine acetyltransferases CBP and p300. Cell Chem Biol. 2020 Dec 31;S2451-9456(20)30513-4. |
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