Introduction：Basic information about CAS 1276553-09-3|PF-4989216, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
| Common Name | PF-4989216 |
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| CAS Number | 1276553-09-3 | Molecular Weight | 380.39900 |
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| Density | 1.5±0.1 g/cm3 | Boiling Point | 693.7±65.0 °C at 760 mmHg |
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| Molecular Formula | C18H13FN6OS | Melting Point | / |
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| MSDS | / | Flash Point | 373.4±34.3 °C |
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Names
| Name | 4-(4-Cyano-2-fluorophenyl)-2-(4-morpholinyl)-5-(1H-1,2,4-triazol-3-yl)-3-thiophenecarbonitrile |
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| Synonym | More Synonyms |
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PF-4989216 BiologicalActivity
| Description | PF-4989216 is a potent and selective PI3Kα inhibitor with a Ki of 0.6 nM. |
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| Related Catalog | Research Areas >>Cancer |
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| Target | PI3Kα:0.6 nM (Ki) mTOR:1440 nM (Ki) |
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| 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]. |
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| 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]. |
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| Cell Assay | MTT and CCK-8 assays are performed to determine the general sensitivities of cells to the tested drugs. The human colon carcinoma S1 cell line and ABCG2-overexpressing subline S1-M1-80 are treated with PF-4989216 (0.1, 1 and 10 μM). The human breast carcinoma MCF-7 and ABCG2-overexpressing sublines MCF7-FLV1000 and MCF7-AdVp3000 are treated with PF-4989216 (0.1, 1, 10 and 100 μM).The parental HEK293 and ABCG2-tranfected R482-HEK293 cells are treated with PF-4989216 (0.01, 0.1, 1 and 10 μM). For the reversal of cytotoxicity assays, PF-4989216 or Ko143 or Lapatinib at a nontoxic concentration is added into the cytotoxicity assay, and the extent of reversal is then calculated[2]. |
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| Animal Admin | Mice[1] For animal studies, 6-8 week old nu/nu athymic female mice are used. Tumors are established by injecting 2×106 cells suspended 1:1 (v/v) with reconstituted basement membrane. For tumor growth inhibition studies, mice with established tumors of ~150 mm3 are randomized. PF-4989216 (Compound 10) is dosed orally (25, 50, 100 and 200 mg/kg) in a mouse PI3K driven NCI-H1975 xenograft tumor model. Tumor dimensions are measured with vernier calipers, and tumor volumes are calculated. Tumor growth inhibition percentage (TGI %) is calculated. |
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| References | [1]. Liu KK, et al. Highly Selective and Potent Thiophenes as PI3K Inhibitors with Oral Antitumor Activity. ACS Med Chem Lett. 2011 Sep 19;2(11):809-813. |
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Chemical & Physical Properties
| Density | 1.5±0.1 g/cm3 |
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| Boiling Point | 693.7±65.0 °C at 760 mmHg |
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| Molecular Formula | C18H13FN6OS |
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| Molecular Weight | 380.39900 |
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| Flash Point | 373.4±34.3 °C |
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| Exact Mass | 380.08600 |
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| PSA | 129.86000 |
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| LogP | 0.48 |
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| Vapour Pressure | 0.0±2.2 mmHg at 25°C |
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| Index of Refraction | 1.696 |
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| InChIKey | MUENOTXSRZEFJV-UHFFFAOYSA-N |
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| SMILES | N#Cc1ccc(-c2c(-c3ncn[nH]3)sc(N3CCOCC3)c2C#N)c(F)c1 |
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| Storage condition | -20℃ |
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Synonyms
| 3-Thiophenecarbonitrile, 4-(4-cyano-2-fluorophenyl)-2-(4-morpholinyl)-5-(1H-1,2,4-triazol-5-yl)- |
| 4-(4-Cyano-2-fluorophenyl)-2-(4-morpholinyl)-5-(1H-1,2,4-triazol-3-yl)-3-thiophenecarbonitrile |
| PF-4989216 |
