[CAS NO. 2093388-62-4] BETd-260
PRODUCTS SPECIFICATIONS [2093388-62-4]
DESCRIPTION [2093388-62-4]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 798.89 |
| Molecular Formula | C43H46N10O6 |
| SMILES | CCN1N=C(C2CC2)C=C1NC3=NC(C(NCCCCCC4=CC=CC5=C4CN(C6C(NC(CC6)=O)=O)C5=O)=O)=NC7=C3C8=CC(OC)=C(C9=C(C)ON=C9C)C=C8N7 |
Summary
IC50 & Target
|
BRD4 <30 pM (IC 50 ) |
BRD2 30-100 pM (IC 50 ) |
BRD3 30-100 pM (IC 50 ) |
In Vitro
BETd-260 (ZBC260; Compound 23) is capable of inducing degradation of BRD2, BRD3, and BRD4 proteins at 30–100 pM in the RS4;11 leukemia cells. BETd-260 shows inhibitory activity against the growth of RS4;11 leukemia cells and MOLM-13 cells with IC
50
s of 51 pM and 2.2 nM, respectively, and induces apoptosis in both RS4;11 and MOLM-13 cell lines at 3-10 nM
[1]
.
BETd-260 reciprocally modulates the expression of several apoptotic genes in HCC cells, i.e., suppressing the expression of anti-apoptotic Mcl-1, Bcl-2, c-Myc, and XIAP, whereas increasing the expression of pro-apoptotic Bad
[2]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
BETd-260 (5 mg/kg, i.v., every other day, thrice a week for 3 weeks) causes rapid tumor regression with a maximum of >90% regression in mice bearing RS4;11 xenograft tumors, and with no body weight loss or other signs of toxicity in mice. BETd-260 (5 mg/kg, i.v.) degrades the BRD2, BRD3, and BRD4 proteins for more than 24 h, with robust cleavage of PARP and caspase-3, and strong down-regulation of c-Myc protein in RS4;11 xenograft mice model [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Solid
Shipping
Shipping with dry ice.
Storage
-80°C, protect from light, stored under nitrogen
Solvent & Solubility
DMSO : 25 mg/mL ( 31.29 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.2517 mL | 6.2587 mL | 12.5174 mL |
| 5 mM | 0.2503 mL | 1.2517 mL | 2.5035 mL |
| 10 mM | 0.1252 mL | 0.6259 mL | 1.2517 mL |
-
1.
-
2.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 0.83 mg/mL (1.04 mM); Clear solution
References
- [1] Zhou B, et al. Discovery of a Small-Molecule Degrader of Bromodomain and Extra-Terminal (BET) Proteins with Picomolar Cellular Potencies and Capable of Achieving Tumor Regression. J Med Chem. 2018 Jan 25;61(2):462-481.
- [2] Zhang H, et al. Targeting BET Proteins With a PROTAC Molecule Elicits Potent Anticancer Activity in HCC Cells. Front Oncol. 2020;9:1471. Published 2020 Jan 14.
