| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
| Targets |
Tubulin
XP-5 targets HDAC6 (histone deacetylase 6), a class IIb histone deacetylase that deacetylates non-histone proteins including α-tubulin and Hsp90. HDAC6 plays a role in regulating cellular processes including protein degradation, cytoskeletal dynamics, and stress responses. By inhibiting HDAC6 with an IC50 of 31 nM and showing excellent selectivity over HDAC3 (SI = 338), XP-5 provides a valuable tool for studying HDAC6-specific biology. |
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| ln Vitro |
A series of 2-phenylthiazole analogues were designed and synthesized as potential histone deacetylase 6 (HDAC6) inhibitors based on compound 12c (an HDAC6/tubulin dual inhibitor discovered by us recently) and CAY10603 (a known HDAC6 inhibitor). Among them, compound XP5 was the most potent HDAC6 inhibitor with an IC50 of 31 nM and excellent HDAC6 selectivity (SI = 338 for HDAC6 over HDAC3). XP5 also displayed high antiproliferative activity against various cancer cell lines including the HDACi-resistant YCC3/7 gastric cancer cells (IC50 = 0.16-2.31 μM), better than CAY10603.
In vitro, XP-5 inhibits HDAC6 with an IC50 of 31 nM and shows excellent HDAC6 selectivity (SI = 338 for HDAC6 over HDAC3). It displays high antiproliferative activity against various cancer cell lines including HDACi-resistant YCC3/7 gastric cancer cells (IC50 = 0.16-2.31 μM). The compound's potent and selective HDAC6 inhibition makes it valuable for cancer research and immunotherapy. |
| ln Vivo |
XP5 (50 mg/kg) exhibited significant antitumor efficacy in a melanoma tumor model with a tumor growth inhibition (TGI) of 63% without apparent toxicity. Moreover, XP5 efficiently enhanced the in vivo antitumor immune response when combined with a small-molecule PD-L1 inhibitor, as demonstrated by the increased tumor-infiltrating lymphocytes and reduced PD-L1 expression levels. Taken together, the above results suggest that XP5 is a promising HDAC6 inhibitor deserving further investigation.
In vivo, XP-5 is orally active. When combined with PD-L1 inhibitors in melanoma, XP-5 enhances antitumor immunity. The compound's oral bioavailability and immunomodulatory effects support its potential for cancer immunotherapy research. However, specific in vivo efficacy data and dosing details have not been extensively detailed in the available literature. |
| Enzyme Assay |
For in vitro enzyme assays, recombinant HDAC6 protein is incubated with a fluorogenic substrate in assay buffer. The test compound is added at various concentrations (0.1-1000 nM). Deacetylase activity is measured by monitoring fluorescence over time. IC50 values are calculated by fitting dose-response curves. Selectivity is assessed by testing against other HDAC isoforms.
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| Cell Assay |
For cell proliferation assays, cancer cell lines (including HDACi-resistant YCC3/7 gastric cancer cells) are seeded in 96-well plates and treated with XP-5 at concentrations ranging from 0.01-10 µM for 72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. IC50 values are calculated from dose-response curves.
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| Animal Protocol |
For in vivo efficacy studies, mouse melanoma models would be used. XP-5 would be administered orally at doses determined from pharmacokinetic studies, alone or in combination with PD-L1 inhibitors. Tumor growth, immune cell infiltration, and antitumor immune responses would be assessed.
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| ADME/Pharmacokinetics |
XP-5 is orally active. It is soluble in DMSO. Storage is recommended at -20°C for 3 years (powder) or -20°C for 6 months (solution). Further detailed PK parameters including half-life, oral bioavailability, and tissue distribution would be required for in vivo studies.
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| Toxicity/Toxicokinetics |
XP-5 is a potent, orally active HDAC6 inhibitor with an IC50 of 31 nM and excellent HDAC6 selectivity (SI = 338 for HDAC6 over HDAC3). It displays high antiproliferative activity against various cancer cell lines and enhances antitumor immunity when combined with PD-L1 inhibitors in melanoma. XP-5 is a research tool and is not approved for clinical use.
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| References |
| CAS # |
2760511-91-7
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| Appearance |
Typically exists as solid at room temperature
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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.) |
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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