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| Targets |
PAFAH1b2 and PAFAH1b3 (platelet-activating factor acetylhydrolases 1b2 and 1b3). P11 is a selective inhibitor of PAFAH1b2 and PAFAH1b3 with IC50 values of approximately 40 nM and 900 nM, respectively. PAFAH1b2 and PAFAH1b3 are catalytic subunits of the PAFAH1b complex, which is a heterotrimeric enzyme composed of two catalytic subunits (α1 and α2, corresponding to PAFAH1b2 and PAFAH1b3) and a regulatory subunit (β). PAFAH1b hydrolyzes the acetyl group at the sn-2 position of platelet-activating factor (PAF) and other oxidized phospholipids, thereby regulating PAF-mediated signaling and inflammation. PAFAH1b also plays a role in brain development and neuronal migration. By inhibiting PAFAH1b2 and PAFAH1b3, P11 blocks PAFAH-mediated hydrolysis of PAF to lyso-PAF, affecting PAF signaling pathways. The compound impairs cancer cell survival, indicating a role for PAFAH1b2/3 in cancer cell biology. P11 is used to study the cellular functions of PAFAH1b2/3 and their roles in cancer cell survival.
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| ln Vitro |
P11 is a selective inhibitor of PAFAH1b2 and PAFAH1b3 with IC50 values of approximately 40 nM and 900 nM, respectively. The compound blocks PAFAH-mediated hydrolysis of PAF to lyso-PAF, affecting PAF signaling pathways. By inhibiting PAFAH1b2 and PAFAH1b3, P11 impairs cancer cell survival. The compound's selectivity for PAFAH1b2 over PAFAH1b3 (approximately 22-fold) makes it a valuable tool for dissecting the specific roles of these two catalytic subunits. P11 is used to study the cellular functions of PAFAH1b2/3 and their roles in cancer cell survival. The compound's inhibitory activity has been characterized in biochemical assays measuring PAFAH enzyme activity. P11 is primarily used in cancer research to study the role of PAFAH1b2/3 in tumorigenesis and to evaluate these enzymes as therapeutic targets.
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| ln Vivo |
P11 has been studied in vivo for its effects on PAFAH activity and cancer cell survival. By inhibiting PAFAH1b2 and PAFAH1b3, P11 impairs cancer cell survival, suggesting potential therapeutic applications in cancer. The compound's effects on tumor growth have been evaluated in preclinical models. Detailed in vivo pharmacokinetic and pharmacodynamic data are limited in publicly available sources. P11 is primarily used as a research tool to study the cellular functions of PAFAH1b2/3 and their roles in cancer cell survival. The compound is for research use only and is not for human therapeutic use.
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| Enzyme Assay |
PAFAH enzyme activity assays are performed using recombinant PAFAH1b2 or PAFAH1b3 enzymes and a substrate such as PAF or a fluorescent PAF analog (e.g., PAF-PC). The enzyme is incubated with the substrate in assay buffer (50 mM Tris-HCl pH 7.4, 150 mM NaCl, 1 mM EDTA) at 37°C for 30-60 minutes. The hydrolysis product (lyso-PAF) is quantified by HPLC, LC-MS, or by using a fluorescent plate reader. P11 is serially diluted in DMSO and added to the reaction mixture to determine IC50 values. The IC50 for PAFAH1b2 is approximately 40 nM, and for PAFAH1b3 is approximately 900 nM. Each concentration is tested in duplicate, and IC50 values are calculated by non-linear regression analysis. Appropriate positive controls (e.g., known PAFAH inhibitors) and vehicle controls are included to validate the assay.
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| Cell Assay |
Cellular PAFAH inhibition is evaluated in various cancer cell lines. Cells are cultured in appropriate media at 37°C with 5% CO₂ and treated with P11 at concentrations ranging from 0.01 to 10 μM for 24-72 hours. PAFAH activity in cell lysates is assessed by measuring hydrolysis of PAF or fluorescent PAF analogs. PAF and lyso-PAF levels are quantified by LC-MS. Cell viability and proliferation are assessed using MTT, CCK-8, or CellTiter-Glo assays. Apoptosis is evaluated by Annexin V/PI staining, caspase-3/7 activity assays, and PARP cleavage Western blotting. Cell cycle analysis is performed by propidium iodide staining and flow cytometry. Each experiment includes vehicle controls (DMSO) and appropriate positive controls (e.g., known PAFAH inhibitors) to validate the assay systems.
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| Animal Protocol |
In vivo efficacy of P11 is evaluated in mouse xenograft models using human cancer cell lines. Tumor cells are implanted subcutaneously in immunodeficient mice. When tumors reach a predetermined size, mice are randomized into treatment and control groups. P11 is administered orally or intraperitoneally at doses determined by preclinical studies. Tumor growth is monitored by caliper measurements. At study endpoint, tumors are harvested for histopathological analysis, immunohistochemistry (Ki67 for proliferation, cleaved caspase-3 for apoptosis), and biochemical assays (PAFAH activity, PAF/lyso-PAF levels). Body weight and clinical signs are monitored throughout the study to assess tolerability. Sample sizes typically range from 6-10 animals per group.
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| ADME/Pharmacokinetics |
Molecular Weight: 503.65. Formula: C30H33NO4S. CAS No.: 942285-55-4. IUPAC Name: (2S,6S)-6-(4-tert-butylphenyl)-2-(4-methylphenyl)-1-(4-methylphenyl)sulfonyl-3,6-dihydro-2H-pyridine-5-carboxylic acid. Synonyms: PAFAH1b2; P11; PAFAH1b2/1b3 Inhibitor. Appearance: Solid. Purity: Typically ≥98%. Solubility: Soluble in DMSO. Storage: Typically at -20°C. P11 is a selective inhibitor of PAFAH1b2 and PAFAH1b3 with IC50 values of approximately 40 nM and 900 nM, respectively.
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| Toxicity/Toxicokinetics |
No comprehensive toxicology data are publicly available for P11. The compound is intended for research use only and has not undergone full preclinical toxicology evaluation required for clinical development. As a PAFAH inhibitor, potential toxicities may include effects on PAF-mediated signaling and inflammation. Standard toxicity studies would include acute toxicity assessment in rodents, repeated dose toxicity studies (14-day and 28-day), and genotoxicity screening (Ames test, micronucleus assay). The compound is for research use only and not for human therapeutic use.
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| References | |
| Additional Infomation |
P11 is also known as PAFAH1b2/1b3 Inhibitor. Its IUPAC name is (2S,6S)-6-(4-tert-butylphenyl)-2-(4-methylphenyl)-1-(4-methylphenyl)sulfonyl-3,6-dihydro-2H-pyridine-5-carboxylic acid. P11 is a selective inhibitor of platelet-activating factor acetylhydrolases 1b2 and 1b3 with IC50 values of approximately 40 nM and 900 nM, respectively. By inhibiting PAFAH1b2 and PAFAH1b3, P11 blocks PAFAH-mediated hydrolysis of PAF to lyso-PAF, affecting PAF signaling pathways and impairing cancer cell survival. P11 is used to study the cellular functions of PAFAH1b2/3 and their roles in cancer cell survival. No clinical trials have been reported for this compound. P11 is for research use only.
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| Molecular Formula |
C30H33NO4S
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| Molecular Weight |
503.65
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| Exact Mass |
503.213
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| CAS # |
942285-55-4
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| PubChem CID |
16656440
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
667.0±65.0 °C at 760 mmHg
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| Flash Point |
357.2±34.3 °C
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| Vapour Pressure |
0.0±2.1 mmHg at 25°C
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| Index of Refraction |
1.607
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| LogP |
8.19
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
36
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| Complexity |
890
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC1=CC=C(C=C1)[C@@H]2CC=C([C@@H](N2S(=O)(=O)C3=CC=C(C=C3)C)C4=CC=C(C=C4)C(C)(C)C)C(=O)O
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| InChi Key |
KUBDPRSHRVANQQ-NSOVKSMOSA-N
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| InChi Code |
InChI=1S/C30H33NO4S/c1-20-6-10-22(11-7-20)27-19-18-26(29(32)33)28(23-12-14-24(15-13-23)30(3,4)5)31(27)36(34,35)25-16-8-21(2)9-17-25/h6-18,27-28H,19H2,1-5H3,(H,32,33)/t27-,28-/m0/s1
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| Chemical Name |
(2S,6S)-6-(4-tert-butylphenyl)-2-(4-methylphenyl)-1-(4-methylphenyl)sulfonyl-3,6-dihydro-2H-pyridine-5-carboxylic acid
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| Synonyms |
PAFAH 1 b 2; PAFAH-1-b-2; PAFAH1b2
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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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9855 mL | 9.9275 mL | 19.8551 mL | |
| 5 mM | 0.3971 mL | 1.9855 mL | 3.9710 mL | |
| 10 mM | 0.1986 mL | 0.9928 mL | 1.9855 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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