PF-4989216Selective oral PI3K inhibitor CAS# 1276553-09-3 |
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Quality Control & MSDS
3D structure
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Number of papers citing our products
| Cas No. | 1276553-09-3 | SDF | Download SDF |
| PubChem ID | 51033720 | Appearance | Powder |
| Formula | C18H13FN6OS | M.Wt | 380.4 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : ≥ 29 mg/mL (76.24 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | 4-(4-cyano-2-fluorophenyl)-2-morpholin-4-yl-5-(1H-1,2,4-triazol-5-yl)thiophene-3-carbonitrile | ||
| SMILES | C1COCCN1C2=C(C(=C(S2)C3=NC=NN3)C4=C(C=C(C=C4)C#N)F)C#N | ||
| Standard InChIKey | MUENOTXSRZEFJV-UHFFFAOYSA-N | ||
| Standard InChI | 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) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | PF-4989216 is a potent and selective PI3Kα inhibitor with a Ki of 0.6 nM.In Vitro:PF-4989216 (Compound 10) has excellent PI3Kα Ki (0.6 nM), good cellular potency (S473 IC50=79 nM), and good selectivity against mTOR (mTOR Ki=1440 nM). PF-4989216 has PI3Kα Ki less than 1 nM and mTOR Ki more than 1 μM. PF-4989216 also has excellent selectivity over 40 other kinases, and no major CYP inhibitions are observed. Less than 30% inhibition is observed in 1A2, 2C9, 2D6, and 3A4 CYP enzymes at 3 μM[1]. The toxicity of PF-4989216 in several drug-sensitive and MDR cancer cell lines, including cells overexpressing ABCB1 or ABCG2, and in HEK293 cells transfected with human ABCB1 or ABCG2 is determined. PF-4989216 inhibits human colon carcinoma S1 cell line and ABCG2-overexpressing subline S1-M1-80 with IC50s of 1.11±0.09 and 6.79±1.00 uM, respectively. PF-4989216 inhibits human breast carcinoma MCF-7 and ABCG2-overexpressing sublines MCF7-FLV1000 and MCF7-AdVp3000 IC50s of 2.30±0.68, 23.26±2.94 and 62.57±5.46 uM, respectively. PF-4989216 inhibits pcDNA-HEK293, ABCB1-transected MDR19-HEK293, ABCG2-tranfected R482-HEK293 cells with IC50s of 0.44±0.05, 0.38±0.06 and 5.05±0.89 uM, respectively[2].In 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]. References: | |||||
PF-4989216 Dilution Calculator
PF-4989216 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.6288 mL | 13.1441 mL | 26.2881 mL | 52.5762 mL | 65.7203 mL |
| 5 mM | 0.5258 mL | 2.6288 mL | 5.2576 mL | 10.5152 mL | 13.1441 mL |
| 10 mM | 0.2629 mL | 1.3144 mL | 2.6288 mL | 5.2576 mL | 6.572 mL |
| 50 mM | 0.0526 mL | 0.2629 mL | 0.5258 mL | 1.0515 mL | 1.3144 mL |
| 100 mM | 0.0263 mL | 0.1314 mL | 0.2629 mL | 0.5258 mL | 0.6572 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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Description:
IC50: 2 nM, 142 nM, 65 nM, 1 nM, and 110 nM for p110α, p110β, p110γ, p110δ, and VPS34, respectively.
The constitutive activation of phosphoinositide 3-kinase (PI3K) occurs frequently in many human tumors through either gene mutation in the p110a catalytic subunit of PI3K or functional loss of tumor suppressor PTEN. Patients with small-cell lung cancer have very poor prognosis and survival rates such that an effective targeted therapy is in strong demand for these patients. PF-4989216 is a selective oral PI3K inhibitor.
In vitro: PF-4989216 inhibited PI3K downstream signaling and led to apoptosis induction, and inhibition in cell viability, transformation, and xenograft tumor growth in small-cell lung cancer (SCLC) harboring PIK3CA mutation. In SCLC with PTEN loss, PF-4989216 also inhibited PI3K signaling but did not induce BCL2-interacting mediator-mediated apoptosis nor was there any effect on cell viability or transformation [1].
In vivo: The mouse in vivo results indicate a good correlation between in vitro and in vivo efficacy, and further confirm that PF-4989216 is an effective drug candidate capable of inducing antitumor activity in mice bearing human SCLC tumors with PIK3CA mutation [1].
Clinical trial: Up to now, PF-4989216 is still in the preclinical development stage.
Reference:
[1] Walls M, Baxi SM, Mehta PP, Liu KK, Zhu J, Estrella H, Li C, Zientek M, Zong Q, Smeal T, Yin MJ. Targeting small cell lung cancer harboring PIK3CA mutation with a selective oral PI3K inhibitor PF-4989216. Clin Cancer Res. 2014 Feb 1;20(3):631-43.
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Targeting small cell lung cancer harboring PIK3CA mutation with a selective oral PI3K inhibitor PF-4989216.[Pubmed:24240111]
Clin Cancer Res. 2014 Feb 1;20(3):631-43.
PURPOSE: Constitutive activation of phosphoinositide 3-kinase (PI3K) occurs frequently in many human tumors via either gene mutation in the p110alpha catalytic subunit of PI3K or functional loss of tumor suppressor PTEN. Patients with small-cell lung cancer (SCLC) have very poor prognosis and survival rates such that an effective targeted therapy is in strong demand for these patients. In this study, we characterized the highly selective oral PI3K inhibitor, PF-4989216, in preclinical SCLC models to investigate whether targeting the PI3K pathway is an effective targeted therapy option for SCLCs that harbor a PIK3CA mutation. EXPERIMENTAL DESIGN: A panel of SCLC cell lines with PIK3CA mutation or PTEN loss were treated with PF-4989216 in several in vitro assays, including PI3K pathway signaling, cell viability, apoptosis, cell-cycle progression, and cell transformation. SCLC cell lines that were sensitive in vitro to PF-4989216 were further evaluated by in vivo animal studies to determine the pharmacokinetic/pharmacodynamic relationship and tumor growth inhibition (TGI) by PF-4989216 treatment. RESULTS: PF-4989216 inhibited PI3K downstream signaling and subsequently led to apoptosis induction, and inhibition in cell viability, transformation, and xenograft tumor growth in SCLCs harboring PIK3CA mutation. In SCLCs with PTEN loss, PF-4989216 also inhibited PI3K signaling but did not induce BCL2-interacting mediator (BIM)-mediated apoptosis nor was there any effect on cell viability or transformation. These results implicate differential tumorigenesis and apoptosis mechanisms in SCLCs harboring PIK3CA mutation versus PTEN loss. CONCLUSIONS: Our results suggest that PF-4989216 is a potential cancer drug candidate for patients with SCLC with PIK3CA mutation but not PTEN loss.
