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Activity Type | Activity Value -log(M) | Mechanism of Action | Activity Reference | Publications (PubMed IDs) |
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SKU | Size | Availability | Price | Qty |
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P414069-1mg | 1mg | In stock | $52.90 | |
P414069-5mg | 5mg | Available within 8-12 weeks(?) Production requires sourcing of materials. We appreciate your patience and understanding. | $216.90 | |
P414069-10mg | 10mg | In stock | $385.90 | |
P414069-25mg | 25mg | In stock | $731.90 | |
P414069-50mg | 50mg | In stock | $1,038.90 |
FGFR1 Selective Inhibitors
Synonyms | PRN1371|1802929-43-6|PRN-1371|8-(3-(4-acryloylpiperazin-1-yl)propyl)-6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-(methylamino)pyrido[2,3-d]pyrimidin-7(8H)-one|S3OPE9IA3Q|6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-(methylamino)-8-[3-(4-prop-2-enoylpiperazin-1-yl)pr |
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Specifications & Purity | Moligand™, ≥98% |
Biochemical and Physiological Mechanisms | PRN1371 is an irreversible covalent FGFR1-4 kinase inhibitor, with IC50s of 0.6, 1.3, 4.1, 19.3 and 8.1 nM for FGFR1, 2, 3, 4 and CSF1R, respectively. |
Storage Temp | Store at -20°C |
Shipped In | Ice chest + Ice pads |
Grade | Moligand™ |
Action Type | INHIBITOR |
Mechanism of action | Inhibitor of fibroblast growth factor receptor 1;Inhibitor of fibroblast growth factor receptor 2;Inhibitor of fibroblast growth factor receptor 3;Inhibitor of fibroblast growth factor receptor 4 |
Product Description | Information PRN1371 is an irreversible covalentFGFR1-4kinase inhibitor, withIC50sof 0.6, 1.3, 4.1, 19.3 and 8.1 nM for FGFR1, 2, 3, 4 and CSF1R, respectively. Targets FGFR1 (Cell-free assay); FGFR2 (Cell-free assay); FGFR3 (Cell-free assay); CSF1R (Cell-free assay); FGFR4 (Cell-free assay) 0.6 nM; 1.3 nM; 4.1 nM; 8.1 nM; 19.3 nM In vitro PRN1371 is an irreversible nanomolar inhibitor of FGFR1−4. PRN1371 presents a unique profile of high biochemical and cellular potency (FGFR1 IC50 = 0.6 nM, SNU16 IC50 = 2.6 nM), prolonged target engagement (FGFR1 occupancy 24 h = 96%), <30% hERG inhibition at 1 μM, and good predicted ADME stability with BME reactivity Kd>100 μM. PRN1371 which maintained high FGFR1 occupancy with improved solubility and exceptional oral bioavailability. In vivo A rat iv (2 mg/kg) PK study of compound 34 showed rapid clearance (Cl = 160 ml/min/kg), yet dosing po (20 mg/kg) demonstrated high oral exposure (AUC = 4348 h·ng/mL) and a reasonable half-life (t1/2 = 3.8 h). PK studies of compound 34 in rat, dog, and cynomolgus monkey showed rapid iv clearance in all species; however there were large species differences in oral exposure and bioavailability for monkey compared to rat and dog. In rat, high exposure upon oral dosing (e.g., Cmax = 1785 ng/mL, AUC = 4348 ng·h/mL) and >100% bioavailability (F) suggested good absorption and partial saturation of clearance mechanisms at the 20 mg/kg dose. Unique to the rat, there is a large difference in half-life between the iv (t1/2 = 0.8 h) and po (t1/2 = 3.8 h) routes of administration, also indicative of possible saturation of a clearance mechanism upon oral dosing. In the dogs, the same methylcellulose suspension formulation used for the rat gave low oral absorption and bioavailability (F < 15%). In SNU16 gastric cancer xenograft mouse model, Compound 34 induced a dose-dependent reduction in tumor volume and up to 68% tumor growth inhibition at the highest dose of 10 mg/kg b.i.d. following 27 days of treatment. All doses were well tolerated with no significant body weight loss. Cell Research(from reference) Cell lines:HUVECs Incubation Time:1 h |
ALogP | 3.438 |
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HBD Count | 1 |
Rotatable Bond | 9 |
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IUPAC Name | 6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-(methylamino)-8-[3-(4-prop-2-enoylpiperazin-1-yl)propyl]pyrido[2,3-d]pyrimidin-7-one |
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INCHI | InChI=1S/C26H30Cl2N6O4/c1-5-20(35)33-11-9-32(10-12-33)7-6-8-34-24-16(15-30-26(29-2)31-24)13-17(25(34)36)21-22(27)18(37-3)14-19(38-4)23(21)28/h5,13-15H,1,6-12H2,2-4H3,(H,29,30,31) |
InChi Key | PUIXMSRTTHLNKI-UHFFFAOYSA-N |
Canonical SMILES | CNC1=NC=C2C=C(C(=O)N(C2=N1)CCCN3CCN(CC3)C(=O)C=C)C4=C(C(=CC(=C4Cl)OC)OC)Cl |
Isomeric SMILES | CNC1=NC=C2C=C(C(=O)N(C2=N1)CCCN3CCN(CC3)C(=O)C=C)C4=C(C(=CC(=C4Cl)OC)OC)Cl |
PubChem CID | 118295624 |
Molecular Weight | 561.46 |
PubChem CID | 118295624 |
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CAS Registry No. | 1802929-43-6 |
RCSB PDB Ligand | GX3 |
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Lot Number | Certificate Type | Date | Item |
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G2221092 | Certificate of Analysis | May 21, 2024 | P414069 |
G2221093 | Certificate of Analysis | May 21, 2024 | P414069 |
G2221097 | Certificate of Analysis | May 21, 2024 | P414069 |
G2221166 | Certificate of Analysis | May 21, 2024 | P414069 |
Solubility | Solubility (25°C) In vitro DMSO: 56 mg/mL (99.73 mM); Water: Insoluble; Ethanol: Insoluble; |
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DMSO(mg / mL) Max Solubility | 100 |
DMSO(mM) Max Solubility | 178.107078 |
Water(mg / mL) Max Solubility | <1 |
Pictogram(s) | GHS07 |
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Signal | Warning |
Hazard Statements | H315:Causes skin irritation H319:Causes serious eye irritation H335:May cause respiratory irritation H302:Harmful if swallowed |
Precautionary Statements | P261:Avoid breathing dust/fume/gas/mist/vapors/spray. P305+P351+P338:IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present and easy to do - continue rinsing. |
1. Brameld KA, Owens TD, Verner E, Venetsanakos E, Bradshaw JM, Phan VT, Tam D, Leung K, Shu J, LaStant J et al.. (2017) Discovery of the Irreversible Covalent FGFR Inhibitor 8-(3-(4-Acryloylpiperazin-1-yl)propyl)-6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-(methylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (PRN1371) for the Treatment of Solid Tumors.. J Med Chem, 60 (15): (6516-6527). [PMID:28665128] |