PF-4989216

Alias: PF 4989216; PF-4989216; PF4989216
Cat No.:V0151 Purity: ≥98%
PF-4989216 is a novel, potent, orally bioactive and selective small molecule inhibitor of PI3K (phosphatidylinositol 3-kinase) with potential anticancer activity.
PF-4989216 Chemical Structure CAS No.: 1276553-09-3
Product category: PI3K
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
5mg
10mg
25mg
50mg
100mg
250mg
Other Sizes
Official Supplier of:
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text

 

  • Business Relationship with 5000+ Clients Globally
  • Major Universities, Research Institutions, Biotech & Pharma
  • Citations by Top Journals: Nature, Cell, Science, etc.
Top Publications Citing lnvivochem Products
Purity & Quality Control Documentation

Purity: ≥98%

Product Description

PF-4989216 is a novel, potent, orally bioactive and selective small molecule inhibitor of PI3K (phosphatidylinositol 3-kinase) with potential anticancer activity. It blocks the PI3K isoforms p110α, p110β, p110γ, p110δ, and VPS34 with respective IC50 values of 2 nM, 142 nM, 65 nM, 1 nM, and 110 nM. In SCLCs with a PIK3CA mutation, PF-4989216 reduced PI3K downstream signaling, which induced apoptosis and inhibited cell viability, transformation, and the growth of xenograft tumors.

Biological Activity I Assay Protocols (From Reference)
Targets
PI3Kα (IC50 = 0.6 nM); mTOR (IC50 = 1440 nM)
ln Vitro
PF-4989216 (Compound 10) has good cellular potency (S473 IC50=79 nM), good selectivity against mTOR (mTOR Ki=1440 nM), and excellent PI3K Ki (0.6 nM). Both PI3Kα and mTOR Ki are greater than or equal to 1 nM in PF-4989216. Additionally, PF-4989216 has excellent selectivity against 40 additional kinases and exhibits no significant CYP inhibition. CYP enzymes 1A2, 2C9, 2D6, and 3A4 exhibit less than 30% inhibition at 3 μM[1]. The drug PF-4989216 is tested for toxicity in a number of drug-sensitive and MDR cancer cell lines, including cancer cells that overexpress ABCB1 or ABCG2 and HEK293 cells that have been transfected with human ABCB1 or ABCG2. With IC50 values of 1.11 0.09 and 6.79 1.00 uM, respectively, PF-4989216 inhibits the ABCG2-overexpressing subline S1-M1-80 of human colon carcinoma S1 cells. The ABCG2-overexpressing sublines MCF7-FLV1000 and MCF7-AdVp3000 of human breast carcinoma MCF-7 are inhibited by PF-4989216, with IC50 values of 2.300.68, 23.262.94, and 62.575.46 uM, respectively. The inhibitory concentrations (IC50s) of PF-4989216 are 0.440.05, 0.380.06, and 5.050.89 uM, respectively, for pcDNA-HEK293, ABCB1-transfected MDR19-HEK293, and ABCG2-tranfected R482-HEK293 cells[2].
ln Vivo
PF-4989216 (Compound 10) is dosed orally in our in vivo antitumor model, PI3K driven NCI-H1975 xenograft tumors. PF-4989216 demonstrates dose responsive tumor growth inhibitory activity from 25 to 200 mg/kg in QD oral dosing[1].
Cell Assay
MTT and CCK-8 assays are performed to determine the general sensitivities of cells to the tested drugs. PF-4989216 (0.1, 1 and 10 M) is used to treat the human colon carcinoma S1 cell line and ABCG2-overexpressing subline S1-M1-80. PF-4989216 (0.1, 1, 10, and 100 M) is used to treat the human breast cancer subtype MCF-7, which overexpresses ABCG2, and the subtypes MCF7-FLV1000 and MCF7-AdVp3000. PF-4989216 (0.01, 0.1, 1 and 10 M) is used to treat the parental HEK293 and ABCG2-tranfected R482-HEK293 cells. When used to reverse cytotoxicity assays, PF-4989216, Ko143, or Lapatinib is added at a nontoxic concentration to the assay, and the degree of reversal is then calculated[2].
Animal Protocol
Mice: For animal studies, 6-8 week old nu/nu athymic female mice are used. When 2 106 cells suspended in a 1:1 (v/v) suspension of reconstituted basement membrane are injected, tumors are created. Mice with established tumors of less than 150 mm3 are randomly assigned for studies on the inhibition of tumor growth. A mouse PI3K-driven NCI-H1975 xenograft tumor model is treated with oral doses of PF-4989216 (Compound 10) of 25, 50, 100, and 200 mg/kg. Vernier calipers are used to measure the tumor's dimensions while also calculating the tumor's volume. The percentage that prevents tumor growth is calculated (TGI%).
References

[1]. Highly Selective and Potent Thiophenes as PI3K Inhibitors with Oral Antitumor Activity. ACS Med Chem Lett. 2011 Sep 19;2(11):809-813.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C18H13N6OFS
Molecular Weight
380.399
Exact Mass
380.08556
Elemental Analysis
C, 56.83; H, 3.44; F, 4.99; N, 22.09; O, 4.21; S, 8.43
CAS #
1276553-09-3
Appearance
Solid powder
SMILES
N#CC1=C(N2CCOCC2)SC(C3=NC=NN3)=C1C4=CC=C(C#N)C=C4F
InChi Key
MUENOTXSRZEFJV-UHFFFAOYSA-N
InChi Code
InChI=1S/C18H13FN6OS/c19-14-7-11(8-20)1-2-12(14)15-13(9-21)18(25-3-5-26-6-4-25)27-16(15)17-22-10-23-24-17/h1-2,7,10H,3-6H2,(H,22,23,24)
Chemical Name
4-(4-cyano-2-fluorophenyl)-2-morpholino-5-(1H-1,2,4-triazol-5-yl)thiophene-3-carbonitrile
Synonyms
PF 4989216; PF-4989216; PF4989216
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 Data
Solubility (In Vitro)
DMSO: ~76 mg/mL (199.8 mM)
Water: <1 mg/mL
Ethanol: 7 mg/mL warming (18.4 mM)
Solubility (In Vivo)
Suspended in 0.5% methylcellulose: 1mg/mL (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.6288 mL 13.1441 mL 26.2881 mL
5 mM 0.5258 mL 2.6288 mL 5.2576 mL
10 mM 0.2629 mL 1.3144 mL 2.6288 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.

Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

  • Calculate the Mass of a compound required to prepare a solution of known volume and concentration
  • Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
  • Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume
An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
  • Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
  • Enter 25 into the Concentration (End) box and select the correct unit (mM)
  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
  • To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
/

Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

  • Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
  • Click the “Calculate” button
  • The answer appears in the Volume (to add to vial) box
In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
+
+
+

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.

Biological Data
Contact Us