PF-3758309
Modify Date: 2024-01-14 00:41:41
PF-3758309 structure
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Common Name | PF-3758309 | ||
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| CAS Number | 898044-15-0 | Molecular Weight | 490.624 | |
| Density | 1.3±0.1 g/cm3 | Boiling Point | 647.9±55.0 °C at 760 mmHg | |
| Molecular Formula | C25H30N8OS | Melting Point | N/A | |
| MSDS | N/A | Flash Point | 345.6±31.5 °C | |
Use of PF-3758309PF-3758309 is an inhbitor of PAK with IC50 of 1.3 nM for PAK4. |
| Name | N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methylthieno[3,2-d]pyrimidin-4-yl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide |
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| Synonym | More Synonyms |
| Description | PF-3758309 is an inhbitor of PAK with IC50 of 1.3 nM for PAK4. |
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| Related Catalog | |
| Target |
PAK4:18.7 nM (Ki) PAK1:13.7 nM (Ki) PAK5:18.1 nM (Ki) PAK6:17.1 nM (Ki) |
| In Vitro | F-3758309 binds directly to PAK4 with an in vitro potency of 2.7-4.5 nM. PF-3758309 has similar enzymatic potency against the kinase domains of the other group B PAKs (PAK5, Ki=18.1±5.1 nM; PAK6, Ki=17.1±5.3 nM) and group A PAK1 (Ki=13.7±1.8 nM), but is less active against the other two group A PAKs (PAK2, IC50=190 nM; PAK3, IC50=99 nM). PAK4 phosphorylates GEF-H1 on a previously characterized serine residue 810 and is inhibited by PF-3758309 (IC50=1.3±0.5 nM). PF-3758309 also inhibits endogenous pGEF-H1 accumulation in HCT116 cells[1]. PF-3758309 is profiled for its growth-inhibitory activity in a panel of 92 tumor cell lines, half of which exhibits IC50 values of less than 10 nM[2]. The proliferation of A549 cells is affected at the treatment with lower dosage (1 μM) of PF-3758309[3]. |
| In Vivo | PF-3758309 (7.5-30 mg/kg BID, p.o.) results in statistically significant tumor growth inhibition (TGI) in five models including HCT116 and A549 models. PF-3758309 (15 mg/kg BID, p.o.) is found to inhibit [3H]FLT uptake 32.5% in the HCT116 tumor xenografts by day 6. PF-3758309 treatment shows a significant increase in the apoptotic marker activated caspase 3 in HCT116 tumors[1]. PF-3758309 (25 mg/kg, p.o.) exhibits antiproliferative effects on cell line xenografts[4]. |
| Cell Assay | CCK-8 assay is performed to determine cell viability. Cells are seeded at a density of 104 cells per well into 96-well plates with 10 % fetal bovine serum and incubated for 24 h. Then, cells are treated with PF-3758309 at various concentrations (0, 0.01, 0.03, 0.1, 0.3, 1, 3, 10, and 30 μM) for 3 days. After the exposure period, the medium is changed and incubated with CCK-8 solution (10 % of the total volume)/well for 30 min. The medium is measured spectrophotometrically at 450 nm and the percentage of viable cells is estimated by comparison with the 0.3 % DMSO control cells. |
| Animal Admin | Five- to six-week-old female athymic nude mice are used. Mice are caged in five groups and kept on a 12-h light/dark cycle and provided with sterilized food and water ad libitum. Animals are allowed to acclimate for at least 7 days before any handling. All CRC cells are harvested in exponential phase growth and resuspended in a 1:1 mixture of serum-free RPMI 1640 and Matrigel. Five to ten million cells per mouse are injected s.c. into the flank using a 23-gage needle. Mice are monitored daily for signs of toxicity and are weighed twice weekly. Tumor size is evaluated twice per week by caliper measurements using the following formula: tumor volume=length×width2×0.52. When tumors reached 150-300 mm3 mice are randomized into two groups with at least 10 tumors per group. Mice are then treated for 14 days with either vehicle control (0.5% methylcellulose), or PF-3758309 (25 mg/kg) twice daily by oral gavage. |
| References |
[2]. Zhao ZS, et al. Do PAKs make good drug targets? F1000 Biol Rep. 2010 Sep 23;2:70. |
| Density | 1.3±0.1 g/cm3 |
|---|---|
| Boiling Point | 647.9±55.0 °C at 760 mmHg |
| Molecular Formula | C25H30N8OS |
| Molecular Weight | 490.624 |
| Flash Point | 345.6±31.5 °C |
| Exact Mass | 490.226318 |
| PSA | 137.03000 |
| LogP | 3.28 |
| Vapour Pressure | 0.0±1.9 mmHg at 25°C |
| Index of Refraction | 1.685 |
| Storage condition | -20℃ |
| cs-0773 |
| Pyrrolo[3,4-c]pyrazole-5(1H)-carboxamide, N-[(1S)-2-(dimethylamino)-1-phenylethyl]-4,6-dihydro-6,6-dimethyl-3-[(2-methylthieno[3,2-d]pyrimidin-4-yl)amino]- |
| N-[(1S)-2-(Dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methylthieno[3,2-d]pyrimidin-4-yl)amino]-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxamide |
| x4z |
| PF-3758309 |