| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
The primary target of XL177A is the deubiquitinating enzyme Ubiquitin-Specific Protease 7 (USP7). USP7 is also known as Herpesvirus-associated ubiquitin-specific protease (HAUSP). By irreversibly inhibiting USP7, the compound prevents the deubiquitination of its substrates, including p53. As a result, p53 levels are stabilized, leading to the activation of p53-dependent cell cycle arrest and apoptosis.
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| ln Vitro |
XL177A, the parent compound of (Rac)-XL177A, is a highly potent and selective irreversible inhibitor of USP7, with an IC50 value of 0.34 nM. It is a strong conjugator of USP7, which stabilizes p53 in cells. The primary mechanism by which XL177A reduces insulin growth is through p53 oscillation. In the human proteome and DUBome, it demonstrates remarkable selectivity for USP7 over other deubiquitinases.
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| ln Vivo |
In vivo, XL177A, the parent compound, elicits cancer cell-killing effects through a p53-dependent mechanism. While specific in vivo protocols are not detailed in the provided summaries, the compound's design as a potent and selective inhibitor suggests its utility in mouse xenograft models of p53 wild-type cancers. By administering (Rac)-XL177A, researchers can evaluate the antitumor efficacy of USP7 inhibition and study the resulting activation of the p53 pathway.
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| Enzyme Assay |
No specific USP7 enzyme assay protocol is described. A typical USP7 inhibition assay: The reaction buffer contains 50 mM Tris-HCl (pH 8.0), 0.5 mM EDTA, 5 mM DTT, 0.01% (v/v) Igepal CA-630, and 0.1 mg/mL BSA. Recombinant USP7 enzyme (0.5-1 nM) is incubated with varying concentrations of the test compound (0.001-1000 nM) for 30 minutes at room temperature. The reaction is initiated by adding the fluorogenic Ubiquitin-Rhodamine 110 substrate (100 nM). Fluorescence (Ex 485 nm, Em 535 nm) is monitored for 60 minutes. The IC50 is calculated from the reaction progress curves.
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| Cell Assay |
A standard cell viability protocol for USP7 inhibitors: p53 wild-type cancer cells (e.g., HCT116 colon cancer cells) are seeded in 96-well plates in McCoy's 5A medium + 10% FBS. The following day, cells are treated with (Rac)-XL177A at concentrations ranging from 0.0001 to 10 uM for 72 hours. Cell viability is measured using the CellTiter-Glo luminescent assay. Apoptosis can be assessed by Western blot for cleaved PARP and cleaved caspase-3. p53 levels are measured by Western blot to confirm target engagement.
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| Animal Protocol |
No in vivo animal protocol was found for (Rac)-XL177A. A general protocol for evaluating USP7 inhibitors in vivo involves establishing subcutaneous xenografts of p53 wild-type cancer cells (e.g., 5×10⁶ HCT116 cells) in the flanks of nude mice. When tumors reach an average volume of 150-200 mm3, mice are randomized (n=8-10 per group) to receive (Rac)-XL177A (e.g., 30 mg/kg, oral or IP) or vehicle daily for 21 days. Tumor volume is measured twice weekly using calipers. Tumor growth inhibition (TGI) is calculated.
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| ADME/Pharmacokinetics |
No PK data was found for (Rac)-XL177A. As a racemic mixture, its PK may differ from the pure enantiomer. For the parent compound XL177A, which is an irreversible covalent inhibitor, the PK is characterized by a short half-life in circulation but prolonged target engagement (due to the covalent bond). It is likely metabolized by liver enzymes and eliminated.
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| Toxicity/Toxicokinetics |
No toxicity data was found for (Rac)-XL177A. Given that it is a potent USP7 inhibitor, its toxicity would likely be related to its on-target activity: stabilization of p53 leading to cell cycle arrest and apoptosis. This could result in significant toxicities to rapidly dividing tissues (e.g., bone marrow, gastrointestinal tract) and potential teratogenic effects.
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| References | |
| Additional Infomation |
(Rac)-XL177A is a research-grade chemical for laboratory use only. Its CAS number is 2417089-73-5, molecular formula is C48H57ClN8O5, and molecular weight is 861.47. It is the racemic isomer of the highly specific USP7 inhibitor XL177A. The compound is intended for non-clinical research in cancer biology and is not for human use. Purity is reported as 98% by HPLC. Each product in one row, fields tab-separated.
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| Molecular Formula |
C48H57CLN8O5
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|---|---|
| Molecular Weight |
861.47
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| Exact Mass |
860.414
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| CAS # |
2417089-73-5
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| Related CAS # |
XL177A;2417089-74-6
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| PubChem CID |
152089451
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| Appearance |
Solid powder
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| Hydrogen Bond Donor Count |
3
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
62
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| Complexity |
1560
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN1CCN(CC1)CCC(=O)NC2=CC3=C(C=C2)C(=O)N(C=N3)CC4(CCN(CC4)C(=O)C(CCCNC(=O)C5=CC6=C(C=C5)C(=C7CCCCC7=N6)Cl)CC8=CC=CC=C8)O
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| InChi Key |
UYJWYMWIVMCGQZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C48H57ClN8O5/c1-54-24-26-55(27-25-54)21-17-43(58)52-36-14-16-39-41(30-36)51-32-57(47(39)61)31-48(62)18-22-56(23-19-48)46(60)35(28-33-8-3-2-4-9-33)10-7-20-50-45(59)34-13-15-38-42(29-34)53-40-12-6-5-11-37(40)44(38)49/h2-4,8-9,13-16,29-30,32,35,62H,5-7,10-12,17-28,31H2,1H3,(H,50,59)(H,52,58)
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| Chemical Name |
N-[4-benzyl-5-[4-hydroxy-4-[[7-[3-(4-methylpiperazin-1-yl)propanoylamino]-4-oxoquinazolin-3-yl]methyl]piperidin-1-yl]-5-oxopentyl]-9-chloro-5,6,7,8-tetrahydroacridine-3-carboxamide
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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 : ~70 mg/mL (~81.26 mM; with ultrasonication)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1608 mL | 5.8040 mL | 11.6081 mL | |
| 5 mM | 0.2322 mL | 1.1608 mL | 2.3216 mL | |
| 10 mM | 0.1161 mL | 0.5804 mL | 1.1608 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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