| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
| Targets |
(S)-PF-06873600 targets cyclin-dependent kinases (CDKs), particularly CDK2, CDK4, and CDK6. These kinases are essential for cell cycle progression, with CDK4 and CDK6 regulating the G1 to S phase transition and CDK2 regulating the S phase progression. By inhibiting these CDKs, (S)-PF-06873600 prevents the phosphorylation of the retinoblastoma protein (Rb) and other substrates, leading to cell cycle arrest and inhibition of cell proliferation. The compound's selectivity for CDKs over other kinases contributes to its anticancer activity.
|
|---|---|
| ln Vitro |
In vitro, (S)-PF-06873600 has been shown to potently inhibit CDK2, CDK4, and CDK6 with IC₅₀ values in the low nanomolar range. The compound inhibits the proliferation of a panel of cancer cell lines, including breast, lung, and colon cancer cells, with IC₅₀ values ranging from 0.1 to 1 µM. (S)-PF-06873600 induces G1 cell cycle arrest and inhibits the phosphorylation of Rb and other CDK substrates. The (S)-enantiomer is significantly more potent than the (R)-enantiomer.
|
| ln Vivo |
In vivo, (S)-PF-06873600 has been shown to inhibit tumor growth in xenograft mouse models. Oral administration of the compound at doses of 10-50 mg/kg resulted in significant tumor growth inhibition in models of breast and lung cancer. The compound was well-tolerated, with no significant body weight loss observed. Biomarker analysis of tumor tissues confirmed the inhibition of Rb phosphorylation and other CDK substrates.
|
| Enzyme Assay |
In vitro enzyme assays for (S)-PF-06873600 involve measuring its inhibition of CDK2, CDK4, and CDK6 kinase activity. The assay is performed using recombinant CDK/cyclin complexes and a peptide substrate in the presence of ATP. The phosphorylation of the substrate is measured using a luminescent or fluorescent readout, and the IC₅₀ value is calculated from the concentration-response curve. Selectivity is assessed by testing the compound against a panel of other kinases.
|
| Cell Assay |
In vitro cellular experiments for (S)-PF-06873600 are performed using cancer cell lines. Cells are treated with varying concentrations of the compound for 48-72 hours, and cell viability is measured using an MTT or CellTiter-Glo assay. The IC₅₀ values are calculated to determine the antiproliferative potency. The effects of (S)-PF-06873600 on the cell cycle and apoptosis are assessed by flow cytometry. The inhibition of Rb phosphorylation and other CDK substrates is assessed by Western blot.
|
| Animal Protocol |
In vivo animal studies for (S)-PF-06873600 are conducted using immunocompromised mice bearing subcutaneous human tumor xenografts. Tumor-bearing mice are randomized into treatment and control groups and administered the compound orally once daily at various doses. Tumor volumes and body weights are measured twice weekly to monitor antitumor efficacy and toxicity. At the end of the study, tumors are collected for histopathological analysis and to measure biomarkers of target engagement.
|
| ADME/Pharmacokinetics |
The pharmacokinetic properties of (S)-PF-06873600 have been characterized in preclinical studies. Following oral administration, the compound is rapidly absorbed, with peak plasma concentrations achieved within 1-2 hours. (S)-PF-06873600 has a moderate half-life of approximately 4-6 hours, allowing for once- or twice-daily dosing. The compound exhibits good oral bioavailability and is extensively metabolized in the liver.
|
| Toxicity/Toxicokinetics |
The toxicity profile of (S)-PF-06873600 has been evaluated in preclinical studies. At therapeutic doses, the compound is generally well-tolerated, with no significant adverse effects observed. The compound does not cause significant body weight loss or clinical signs of toxicity. Hematological and serum biochemical parameters remain within normal ranges. The overall safety profile is considered favorable.
|
| Additional Infomation |
(S)-PF-06873600 is a potent CDK2/4/6 inhibitor with significant antitumor activity. As the (S)-enantiomer, it is the active form of the compound. By inhibiting CDKs, (S)-PF-06873600 induces cell cycle arrest and inhibits the proliferation of cancer cells. Its favorable pharmacokinetic and safety profiles support its further development as an anticancer agent for the treatment of various cancers.
|
| Molecular Formula |
C20H27F2N5O4S
|
|---|---|
| Molecular Weight |
471.521290063858
|
| Exact Mass |
471.175
|
| CAS # |
2185859-59-8
|
| PubChem CID |
134253135
|
| Appearance |
Solid powder
|
| LogP |
1.4
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
32
|
| Complexity |
859
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
S(C)(N1CCC(CC1)NC1=NC=C2C=C(C(F)F)C(N(C2=N1)[C@H]1CCC[C@]1(C)O)=O)(=O)=O
|
| InChi Key |
QIEKHLDZKRQLLN-YWZLYKJASA-N
|
| InChi Code |
InChI=1S/C20H27F2N5O4S/c1-20(29)7-3-4-15(20)27-17-12(10-14(16(21)22)18(27)28)11-23-19(25-17)24-13-5-8-26(9-6-13)32(2,30)31/h10-11,13,15-16,29H,3-9H2,1-2H3,(H,23,24,25)/t15-,20-/m0/s1
|
| Chemical Name |
6-(difluoromethyl)-8-[(1S,2S)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one
|
| Synonyms |
(S) PF06873600 (S) PF 06873600
|
| 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 | 2.1208 mL | 10.6040 mL | 21.2080 mL | |
| 5 mM | 0.4242 mL | 2.1208 mL | 4.2416 mL | |
| 10 mM | 0.2121 mL | 1.0604 mL | 2.1208 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
