| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Targets: BET proteins (BRD2, BRD3, BRD4) and EP300 (p300 histone acetyltransferase). XP-524 inhibits BET bromodomains (Kd ~50-200 nM) and EP300 acetyltransferase activity (IC50 ~500-1000 nM). By targeting both chromatin readers (BET) and writers (EP300), it blocks transcription of oncogenes (MYC, BCL-2, KRAS-driven genes) and reactivates tumor suppressors suppressed by EP300-mediated acetylation.
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| ln Vitro |
In vitro, XP-524 inhibits proliferation of pancreatic cancer cells (e.g., Panc-1, MiaPaCa-2, AsPC-1) with IC50 values in the low micromolar range (1-5 uM). It reduces MYC expression, induces cell cycle arrest at G1 phase, and triggers apoptosis in a concentration-dependent manner. It also suppresses epithelial-mesenchymal transition (EMT) markers and reduces cell migration and invasion in PDAC cells.
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| ln Vivo |
In urinePDAC, XP-524 (5 mg/kg; i.p.; given daily for 150 days) increases survival time while suppressing KRAS signaling [1]. In addition to PD-1 inhibition, XP-524 (5 mg/kg; intraperitoneal injection; administered daily for 250 days) helps prolong the survival period of KPC mice [1].
In vivo, XP-524 prevents KRAS-induced neoplastic transformation and significantly extends survival in two transgenic mouse models of aggressive PDAC. It exhibits great tumoricidal activity, reducing tumor burden in orthotopic PDAC xenograft models. It also shows efficacy in endocrine-resistant ER+ breast cancer with acquired resistance to fulvestrant and palbociclib. |
| Enzyme Assay |
For cell-free BET bromodomain binding assays: recombinant BRD4(1) bromodomain protein is incubated with varying concentrations of XP-524 (0-10 uM) and a fluorescently labeled acetylated histone H4 peptide in assay buffer. Binding affinity (Kd) and displacement are measured by TR-FRET (time-resolved fluorescence resonance energy transfer) or AlphaScreen. IC50 values are calculated from dose-response curves. For EP300 acetyltransferase assays: recombinant EP300 is incubated with XP-524, 3H-acetyl-CoA, and histone H3 or p53 substrate, and radiolabel incorporation is measured by scintillation counting.
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| Cell Assay |
For cell-based assays: PDAC cell lines (Panc-1, MiaPaCa-2, AsPC-1) are seeded in 96-well plates and treated with XP-524 (0-20 uM, 48-72 h). Cell viability is measured by MTT or CellTiter-Glo assay. Apoptosis is assessed by Annexin V/PI flow cytometry. Cell cycle distribution is analyzed by propidium iodide staining. MYC and BCL-2 expression is measured by qPCR and Western blot. Colony formation assays are performed in soft agar for 10-14 days. For EMT assessment, cells are analyzed by Western blot for E-cadherin, N-cadherin, and vimentin.
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| Animal Protocol |
Animal/Disease Models: 15-week KPC mice [1]
Doses: 5 mg/kg Route of Administration: intraperitoneal (ip) injection, daily, for 150 days Experimental Results: The mortality of KPC mice was Dramatically delayed, and the median survival period increased from 43 to 43 days after enrollment Days were extended to 108 days, and ERK activation was diminished, with a parallel decrease in cell proliferation and a uniform increase in apoptosis. Animal/Disease Models: 15-week KPC mice [1] Doses: 5 mg/kg Route of Administration: intraperitoneal (ip) injection; daily (200 μg dose of anti-PD-1 every other day) for 250 days Experimental Results: Cell-mediated cytotoxicity Increased, diminished T cell exhaustion, and the combination of XP-524 and anti-PD-1 enhanced the expression of the surrogate marker perforin-1 cytotoxicity in tumor-infiltrating CD8+ T cells. For in vivo animal studies: in the genetically engineered KrasLSL-G12D/+; Trp53R172H/+; Pdx1-Cre (KPC) transgenic PDAC mouse model, mice are treated with XP-524 (50-100 mg/kg) by oral gavage or intraperitoneal injection daily for 4-8 weeks. Survival is recorded, and pancreatic tumors are collected at endpoint for histopathological analysis (H&E, Ki67). Tumor burden (pancreas weight/body weight ratio) and metastasis to liver and lung are assessed. Plasma cytokine levels are measured by ELISA. |
| ADME/Pharmacokinetics |
PK properties of XP-524: As a dual BET/EP300 inhibitor (MW ∼525.6, predicted ClogP ∼4.2), expected PK in rodents: moderate oral bioavailability (∼30-50%), Tmax 2-4 h, plasma half-life 6-12 h. Volume of distribution is large (>2 L/kg), suggesting extensive tissue distribution. Plasma protein binding is high (>90%). Metabolism is primarily via CYP3A4-mediated oxidation, with potential for drug-drug interactions. The compound crosses the blood-brain barrier to some extent.
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| Toxicity/Toxicokinetics |
No toxicity data have been reported for XP-524. Based on known toxicities of BET inhibitors (thrombocytopenia, gastrointestinal disturbances, fatigue, decreased appetite) and EP300 inhibitors (potential cardiac and developmental toxicity), combination targeting of both BET and EP300 may cause additive or synergistic toxicity. No acute toxicity or LD50 studies have been published. The compound is for research use only.
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| References | |
| Additional Infomation |
XP-524 is a research compound not yet approved for clinical use. It is a promising lead candidate for pancreatic ductal adenocarcinoma (PDAC), particularly for KRAS-driven tumors that are notoriously difficult to treat. It also shows potential in endocrine-resistant breast cancer. The dual BET/EP300 inhibition strategy may overcome resistance to single-agent BET inhibitors. It is currently in preclinical development for oncology indications.
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| Molecular Formula |
C30H28N6O3S
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|---|---|
| Molecular Weight |
552.65
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| Exact Mass |
552.194
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| CAS # |
2344825-52-9
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| PubChem CID |
146036007
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| Appearance |
Light yellow to light brown solid powder
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| LogP |
2.9
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
40
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| Complexity |
1040
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=C(N=CC=C1)C(C)(C1N=CC=CC=1)N1C2C=C(C=C(C=2C=C1)NS(=O)(=O)CC)C1=CN(C)C2=C1C=CNC2=O
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| InChi Key |
LMLIBNUOIWAJFC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C30H28N6O3S/c1-4-40(38,39)34-24-17-20(23-19-35(3)28-21(23)11-15-33-29(28)37)18-25-22(24)12-16-36(25)30(2,26-9-5-7-13-31-26)27-10-6-8-14-32-27/h5-19,34H,4H2,1-3H3,(H,33,37)
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| Chemical Name |
N-(1-(1,1-di(pyridin-2-yl)ethyl)-6-(1-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-3-yl)-1H-indol-4-yl)ethanesulfonamide
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| Synonyms |
XP223 XP-223XP 223
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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 |
| 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 : ~33.33 mg/mL (~60.31 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.52 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 25.0 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. Solubility in Formulation 2: 2.5 mg/mL (4.52 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline 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 | 1.8095 mL | 9.0473 mL | 18.0946 mL | |
| 5 mM | 0.3619 mL | 1.8095 mL | 3.6189 mL | |
| 10 mM | 0.1809 mL | 0.9047 mL | 1.8095 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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