| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
BETd-246 targets BET family proteins, including BRD2, BRD3, and BRD4. It is a PROTAC that recruits an E3 ubiquitin ligase (Cereblon) to BET proteins, inducing their ubiquitination and subsequent proteasomal degradation. By depleting BET proteins, BETd-246 suppresses BET-mediated transcriptional regulation and tumor-associated signaling pathways. The compound completely and selectively depletes BRD2.
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|---|---|
| ln Vitro |
In test TNBC cell lines, BETd-246 treatment (0-100 nM, 1-3 hours) causes dose-dependent BRD2, BRD3, and BRD4 depletion (30-100 nM for 1 hour or 10-30 nM for 3 hours of incubation). In the MDA-MB-468 cell line, BETd-246 (100 nM, 24/48 hours) has potent growth inhibitory and apoptosis-inducing properties. In every TNBC cell line tested, BETd-246 causes the MCL1 protein to be rapidly and time-dependently downregulated. More apoptosis was triggered by BETd-246 than by BETi-211. In TNBC cell lines, BETd-246 (100 nM, 24 h) significantly promotes cell cycle arrest and apoptosis [1].
In vitro, BETd-246 demonstrates potent antiproliferative activity against human Burkitt's lymphoma cells with a GI50 of 0.4 μM. It shows an IC50 of <10 nM against MDA-MB-468 cells. BETd-246 targets Merkel cell carcinoma (MCC) significantly more sensitively than BET inhibitor treatment, resulting in a loss of "MCC signature" genes. It exhibits superior selectivity and potency compared to other BET degraders. |
| ln Vivo |
The administration of BETd-246 (5 mg/kg, intravenous injection, three times per week for three weeks) substantially reduced the growth of WHIM24 tumors, exhibiting anti-tumor efficacy comparable to that of BETi-211 at higher doses and more frequent administration. Partial tumor regression was induced after therapy at a dose of 10 mg/kg without any apparent side effects. BETd-246 drug exposure in xenograft tumor tissue was very low in the MDA-M-231 and MDA-MB-468 models [1].
Specific in vivo activity data for BETd-246 are not detailed in the available sources. As a second-generation BET degrader with superior potency and antitumor activity in vitro, the compound is expected to have significant in vivo efficacy in various cancer models. BET degraders have shown promising anti-tumor activity in preclinical models of hematological malignancies and solid tumors. |
| Enzyme Assay |
The BET binding and degradation assay for BETd-246 involves measuring the compound's ability to bind to BET bromodomains and induce BET protein degradation. Binding affinity is assessed using a fluorescence polarization or TR-FRET assay with recombinant BET bromodomains. Degradation is evaluated by treating cells with BETd-246 and measuring BRD2, BRD3, and BRD4 protein levels by Western blot. The DC50 for degradation is calculated from dose-response curves.
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| Cell Assay |
Cell proliferation analysis [1]
Cell Types: MDA-MB-468 Cell Tested Concentrations: 100 nM Incubation Duration: 24 or 48 hrs (hours) Experimental Results: demonstrated strong growth inhibition and apoptosis-inducing activity in TNBC cell lines. Cell cycle analysis[1] Cell Types: Human TNBC Cell Tested Concentrations: 100 nM Incubation Duration: 24 hrs (hours) Experimental Results: Induced significant cell cycle arrest and apoptosis in TNBC cell line. Western Blot Analysis[1] Cell Types: Human TNBC Cell Tested Concentrations: 0-100 nM Incubation Duration: 1-3 hrs (hours) Experimental Results: Caused dose-dependent depletion of BRD2, BRD3 and BRD4. To evaluate the cellular activity of BETd-246, cancer cell lines (such as Burkitt's lymphoma or triple-negative breast cancer cells) are seeded in 96-well plates and treated with varying concentrations of BETd-246. Cell proliferation is measured using MTT or CellTiter-Glo assays after 72 hours of treatment. GI50 and IC50 values are calculated from dose-response curves. BET protein levels are assessed by Western blot to confirm degradation. Target gene expression (such as MYC) is measured by quantitative RT-PCR. |
| Animal Protocol |
Animal/Disease Models: The “Washington Human Mouse (WHIM)” (PDX) model was developed from patients with refractory breast cancer (ESRE380Q, PR- and HER2-) [1].
Doses: 5, 10 mg/kg Route of Administration: intravenously (iv) (iv)(iv), 3 times a week for 3 weeks. Experimental Results: Effectively inhibited WHIM24 tumor growth. Specific in vivo animal experiment protocols for BETd-246 are not detailed in the available sources. As a BET degrader, the compound would typically be evaluated in xenograft models using human cancer cell lines implanted subcutaneously into immunodeficient mice. BETd-246 would be administered orally or intraperitoneally, and tumor growth inhibition and BET protein degradation in tumor tissue would be measured. |
| ADME/Pharmacokinetics |
Specific pharmacokinetic data for BETd-246 are not provided in the available sources. The compound has a molecular weight of 946.02 and a molecular formula of C48H55N11O10. It is a second-generation PROTAC-based BET degrader. Standard pharmacokinetic studies would typically involve administering the compound to rodents and measuring plasma and tissue concentrations over time using LC-MS/MS to determine key PK parameters.
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| Toxicity/Toxicokinetics |
Specific toxicity data for BETd-246 are not provided in the available sources. As a research compound, it is intended for laboratory use only and is not approved for human therapeutic applications. The compound is a potent BET degrader, and its toxicity profile would be expected to reflect its mechanism of action. Standard safety precautions should be followed when handling this compound.
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| References | |
| Additional Infomation |
BETd-246 is a second-generation, PROTAC-based BET bromodomain (BRD) degrader that exhibits superior selectivity, potency, and antitumor activity. It completely and selectively depletes BRD2. It targets Merkel cell carcinoma significantly more sensitively than BET inhibitor treatment. The compound has a molecular formula of C48H55N11O10 and a molecular weight of 946.02.
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| Molecular Formula |
C48H55N11O10
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|---|---|
| Molecular Weight |
946.018010377884
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| Exact Mass |
945.413
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| CAS # |
2140289-17-2
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| PubChem CID |
131698640
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.6
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
16
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| Rotatable Bond Count |
23
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| Heavy Atom Count |
69
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| Complexity |
1800
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O(C)C1C(C2C(C)=NOC=2C)=CC2=C(C=1)C1=C(N=C(C(NCCCOCCOCCOCCCNC3=CC=CC4C(N(C(C=43)=O)C3C(NC(CC3)=O)=O)=O)=O)N=C1NC1=CC(C3CC3)=NN1CC)N2
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| InChi Key |
XEJMFVWHCPNMRS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C48H55N11O10/c1-5-58-37(25-33(56-58)28-11-12-28)52-43-41-30-24-36(65-4)31(39-26(2)57-69-27(39)3)23-34(30)51-42(41)54-44(55-43)46(62)50-16-8-18-67-20-22-68-21-19-66-17-7-15-49-32-10-6-9-29-40(32)48(64)59(47(29)63)35-13-14-38(60)53-45(35)61/h6,9-10,23-25,28,35,49H,5,7-8,11-22H2,1-4H3,(H,50,62)(H,53,60,61)(H2,51,52,54,55)
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| Chemical Name |
4-[(5-cyclopropyl-2-ethylpyrazol-3-yl)amino]-7-(3,5-dimethyl-1,2-oxazol-4-yl)-N-[3-[2-[2-[3-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]propoxy]ethoxy]ethoxy]propyl]-6-methoxy-9H-pyrimido[4,5-b]indole-2-carboxamide
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| Synonyms |
BETd-246; BETd246; BETd 246
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~200 mg/mL (~211.41 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (5.29 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.0571 mL | 5.2853 mL | 10.5706 mL | |
| 5 mM | 0.2114 mL | 1.0571 mL | 2.1141 mL | |
| 10 mM | 0.1057 mL | 0.5285 mL | 1.0571 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 BETd-246 is a potent and highly selective degrader of BET proteins.Cancer Res.2017 May 1;77(9):2476-2487. |
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 BETd-246 displays potent antiproliferative and apoptosis induction activities in TNBC cell lines.Cancer Res.2017 May 1;77(9):2476-2487. |
 BET inhibitor and degrader elicit extensive but different transcriptome changes in TNBC cells.Cancer Res.2017 May 1;77(9):2476-2487. |
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