| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
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| 5mg | |||
| 10mg | |||
| Other Sizes |
| Targets |
Cereblon
CBP (CREB-binding protein) and p300 (histone acetyltransferases/transcriptional coactivators). |
|---|---|
| ln Vitro |
LNCaP prostate cancer cell viability was inhibited by PROTAC CBP/P300 Degrader-1 (IC50=0.4 nM). P300 degradation (≥ 80%) is induced by PROTAC CBP/P300 Degrader-1 (10 nM) [1]. HHEL, NOMO-1, MOLM-13, HL-60, MEG-01, MM.IS, MM.1R, NCL-H929, RPM-8226, AMO -1, WSU-DLCL2, Karpas-422, Pfeiffer, SU-DHL-1, LNCap clone FGC, VCap; 22RV1, NCI-H520, NCI-H703, LK-2, MCE-7, and SK-BR-3 cells. The IC50 range is 0.1-141.4 nM.
PROTAC CBP/P300 Degrader-1 induces robust degradation of p300 with ≥80% depletion at a concentration of 10 nM. It exhibits significant potency in reducing cell viability across various cancer cell lines. In LNCaP prostate cancer cells, the compound potently inhibits cell viability with an IC50 of 0.4 nM. It is a highly effective PROTAC for degrading CBP and p300 proteins. |
| ln Vivo |
In the LNCaP prostate cancer xenograft mouse model, PROTAC CBP/P300 Degrader-1 (administered intraperitoneally (IP) at 5 mg/kg, once daily for 14 days) demonstrated potent anti-tumor efficacy. Treated animals showed significant tumor growth inhibition (TGI) with partial regressions observed. The compound is designed to modulate the activity of key transcription coactivators in vivo, facilitating investigations into oncogenic pathways and potential treatment strategies.
|
| Enzyme Assay |
Assay: In vitro ternary complex formation assay. Protocol: Biotinylated CBP or p300 protein is incubated with recombinant cereblon (CRBN), varying concentrations of PROTAC CBP/P300 Degrader-1 (0.1-1000 nM), and streptavidin-coated donor beads and nickel-chelate acceptor beads in AlphaLISA buffer. The formation of the PROTAC-mediated ternary complex brings donor and acceptor beads into proximity, generating a luminescent signal measured at 615 nm.
|
| Cell Assay |
Cells: Various cancer cell lines (e.g., LNCaP, HEK293T, and solid tumor lines). Protocol: For degradation assays, cells are treated with PROTAC CBP/P300 Degrader-1 (0.1-1000 nM) for 16-24 hours. Cell lysates are analyzed by Western blot for CBP, p300, and loading controls (e.g., GAPDH, tubulin). For viability assays, cells are treated with 0.01-10000 nM for 72-96 hours, and viability is measured using CellTiter-Glo or MTT assays. DC50 and IC50 are calculated.
|
| Animal Protocol |
Animal Model: LNCaP prostate cancer xenograft model in mice. Protocol: Female BALB/c nude mice bearing subcutaneous LNCaP tumors are treated with PROTAC CBP/P300 Degrader-1 via intraperitoneal (IP) injection at doses of 3 or 5 mg/kg once daily for 14 days. Tumor volume and body weight are measured every 2-3 days. At study endpoint, tumors are excised and analyzed for CBP and p300 degradation by Western blot, and for proliferation (Ki67) and apoptosis (TUNEL) by immunohistochemistry.
|
| ADME/Pharmacokinetics |
No specific PK data; as a PROTAC with a high molecular weight (893.98 g/mol), PROTAC CBP/P300 Degrader-1 is unlikely to have good oral bioavailability. In preclinical studies, it is typically administered via intraperitoneal (IP) injection. Its distribution, metabolism, and excretion are characteristic of PROTAC molecules: short plasma half-life (1-4 hours), high clearance, and extensive tissue distribution due to high lipophilicity.
|
| Toxicity/Toxicokinetics |
No specific toxicity data; in animal studies at efficacious doses (3-5 mg/kg IP), PROTAC CBP/P300 Degrader-1 was generally well-tolerated. However, given the critical role of CBP and p300 in gene regulation, hematopoiesis, and cell growth, on-target degradation in healthy tissues could lead to dose-limiting toxicities such as myelosuppression or gastrointestinal toxicity. Comprehensive toxicological studies are not yet published.
|
| References | |
| Additional Infomation |
PROTAC CBP/P300 Degrader-1 was developed as a chemical probe to study the role of CBP and p300 in cancer. It is a CRBN-based PROTAC. Unlike small-molecule inhibitors that only block the catalytic activity of CBP/p300, this degrader eliminates the entire protein, thereby disrupting both catalytic and non-catalytic (scaffolding) functions. It is not approved for human use and is strictly a research tool for oncology and epigenetics.
|
| Molecular Formula |
C46H53F2N11O6
|
|---|---|
| Molecular Weight |
893.98
|
| Exact Mass |
893.414
|
| CAS # |
2484739-48-0
|
| PubChem CID |
162642580
|
| Appearance |
Light yellow to green yellow solid powder
|
| LogP |
3.8
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
12
|
| Rotatable Bond Count |
12
|
| Heavy Atom Count |
65
|
| Complexity |
1790
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1N(C(NC)=O)CCC2N(C3CCN(C(=O)CCCCCNC4=CC=CC5=C4C(=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
|
| InChi Key |
KOXRGDZBEAJAKE-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C46H53F2N11O6/c1-49-46(65)56-21-16-35-33(26-56)42(57-18-7-8-27-22-31(28-24-51-54(2)25-28)32(41(47)48)23-37(27)57)53-59(35)29-14-19-55(20-15-29)39(61)11-4-3-5-17-50-34-10-6-9-30-40(34)45(64)58(44(30)63)36-12-13-38(60)52-43(36)62/h6,9-10,22-25,29,36,41,50H,3-5,7-8,11-21,26H2,1-2H3,(H,49,65)(H,52,60,62)
|
| Chemical Name |
3-[7-(difluoromethyl)-6-(1-methylpyrazol-4-yl)-3,4-dihydro-2H-quinolin-1-yl]-1-[1-[6-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]hexanoyl]piperidin-4-yl]-N-methyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carboxamide
|
| HS Tariff Code |
2934.99.9001
|
| 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 and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : 173.33 mg/mL (193.89 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 6.5 mg/mL (7.27 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 65.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1186 mL | 5.5930 mL | 11.1859 mL | |
| 5 mM | 0.2237 mL | 1.1186 mL | 2.2372 mL | |
| 10 mM | 0.1119 mL | 0.5593 mL | 1.1186 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.
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