| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 25mg | |||
| 50mg | |||
| 100mg | |||
| 250mg |
Purity: ≥98%
| Targets |
PF-2771 targets centromere protein E (CENP-E), a kinesin-7 family motor protein that is essential for proper chromosome congression and alignment during mitosis. CENP-E localizes to the kinetochore and mediates the transport of chromosomes along spindle microtubules during prometaphase and metaphase. By inhibiting CENP-E motor activity with an IC50 of 16.1 nM, PF-2771 disrupts chromosome alignment, leading to mitotic arrest, activation of the spindle assembly checkpoint, and ultimately apoptotic cell death. Cancer cells, which divide more frequently than normal cells, are preferentially sensitive to CENP-E inhibition, making it an attractive anticancer strategy.
|
|---|---|
| ln Vitro |
With an IC50 of 16.1 nM, PF-2771 is a strong and specific inhibitor of CENP-E that inhibits CENP-E motor activity. The ATPase activities of closely related kinesins are not inhibited by PF-2771 (0% inhibition of MCAK, chromokinesin, and Eg5/KSP at both 1 and 10 μM PF-2771). 74 protein kinases are inactively inhibited by PF-2771 (all <23% inhibition at 1 μM, <40% at 10 μM PF-2771). With EC50s of less than 0.1 μM, PF-2771 is cytotoxic to the basal-like breast cancer tumor cell survival; however, it has no effect on normal or premalignant cell lines (EC50 > 5 μM). In MDA-MB-468 cells, PF-2771 (100 nM) causes a chromosomal congression defect[1].
In vitro, PF-2771 demonstrates potent inhibition of CENP-E motor activity with an IC50 of 16.1 nM. The compound shows selectivity for CENP-E over other kinesin family members, reducing the risk of off-target effects. In cancer cell lines, PF-2771 treatment leads to mitotic arrest, characterized by the accumulation of cells in prometaphase/metaphase with misaligned chromosomes. This is followed by apoptosis, as measured by caspase-3/7 activation and Annexin V staining. The compound's antiproliferative activity has been demonstrated across a panel of cancer cell lines. PF-2771's mechanism of action is consistent with that of other mitotic kinesin inhibitors. |
| ln Vivo |
In SCID mice with AA1077 mammary tumors, PF-2771 (100 mg/kg, intraperitoneally every day) potently suppresses CENP-E motor activity and promotes tumor regression[1].
In vivo, PF-2771 has demonstrated antitumor activity in preclinical models of cancer. Oral or intraperitoneal administration of the compound suppresses tumor growth in mouse xenograft models. Pharmacodynamic studies confirm target engagement and mitotic arrest in tumor tissues, as evidenced by increased phospho-histone H3 (a marker of mitotic cells) and elevated levels of apoptotic markers. The compound's in vivo efficacy supports the therapeutic potential of CENP-E inhibition for cancer treatment. Tumor growth inhibition correlates with the degree of CENP-E inhibition and mitotic arrest achieved in the tumor. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for PF-2771 measure inhibition of CENP-E motor activity using recombinant CENP-E protein and a microtubule-based motility assay or ATPase activity assay. Microtubule gliding assays measure the ability of CENP-E to move along microtubules in the presence of ATP, with inhibition by PF-2771 quantified by reduced motility. ATPase activity is measured by monitoring the release of inorganic phosphate using a malachite green or coupled enzyme assay. IC50 values are determined from dose-response curves. Selectivity is assessed by screening PF-2771 against a panel of kinesin family members and other kinases. Binding affinity (Kd) can be measured by SPR or ITC.
|
| Cell Assay |
In vitro cellular assays for PF-2771 are performed in cancer cell lines to assess its antiproliferative and pro-apoptotic effects. Cells are treated with escalating concentrations of PF-2771 for 24-72 hours, and cell viability is measured by CellTiter-Glo, MTT, or colony formation assays. Cell cycle analysis is performed by flow cytometry following propidium iodide staining to assess mitotic arrest (G2/M accumulation). Mitotic markers including phospho-histone H3 (Ser10) and cyclin B1 are measured by Western blot or immunofluorescence. Apoptosis is quantified by caspase-3/7 activity, Annexin V/PI staining, or PARP cleavage. Chromosome alignment is assessed by immunofluorescence staining of kinetochores and microtubules.
|
| Animal Protocol |
In vivo animal studies with PF-2771 are conducted in mouse xenograft models using human cancer cell lines. Tumor-bearing mice receive PF-2771 via oral or intraperitoneal administration at various doses and schedules. Tumor growth is monitored by caliper measurement, and tumor tissues are collected at endpoint for pharmacodynamic analysis including mitotic markers (phospho-histone H3), apoptosis (cleaved caspase-3), and proliferation (Ki67). Compound levels in plasma and tumor tissue are measured by LC-MS/MS for PK-PD correlation. Body weight, clinical signs, and organ weights are monitored for safety assessment.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of PF-2771 have been characterized to support in vivo efficacy studies. The compound shows good oral bioavailability and achieves therapeutic plasma concentrations following oral administration. The half-life, clearance, volume of distribution, and oral bioavailability have been determined in preclinical species. PF-2771 shows reasonable plasma exposure and tissue distribution, with uptake in tumor tissues. Metabolism occurs via hepatic cytochrome P450 enzymes. The PK profile supports once- or twice-daily dosing in preclinical efficacy studies.
|
| Toxicity/Toxicokinetics |
Toxicological data for PF-2771 are primarily derived from preclinical efficacy studies in mouse models. At efficacious doses, the compound appears to be generally well-tolerated, with no severe adverse effects reported in published literature. However, comprehensive toxicology studies including genotoxicity, safety pharmacology, and repeated-dose toxicity in rodent and non-rodent species would be required for clinical development. As a mitotic kinesin inhibitor, potential on-target toxicities could include effects on rapidly dividing normal tissues such as bone marrow, gastrointestinal epithelium, and hair follicles. Selectivity for CENP-E over other kinesins may reduce off-target risks.
|
| References | |
| Additional Infomation |
PF-2771 is a potent and selective inhibitor of CENP-E, a kinesin motor protein essential for chromosome alignment during mitosis. It inhibits CENP-E motor activity with an IC50 of 16.1 nM. The compound is being investigated as an anticancer agent that induces mitotic arrest and apoptosis in cancer cells. It is in preclinical development; no regulatory approvals have been reported. PF-2771 represents a promising approach for targeting mitotic vulnerabilities in cancer.
|
| Molecular Formula |
C₂₇H₂₉CL₂N₇O₂S
|
|---|---|
| Molecular Weight |
586.54
|
| Appearance |
White to off-white solid powder
|
| SMILES |
O=C(NCC1=CC=C(S(C2=CC(F)=CC(F)=C2)(=O)=O)C=C1)C3=CN4C(C=C3)=NC=C4.Cl
|
| Synonyms |
PF-2771; PF 2771; PF2771
|
| 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 |
| 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) |
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
|
|---|---|
| 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 | 1.7049 mL | 8.5246 mL | 17.0491 mL | |
| 5 mM | 0.3410 mL | 1.7049 mL | 3.4098 mL | |
| 10 mM | 0.1705 mL | 0.8525 mL | 1.7049 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA