PRN1371 - Moligand™, 10mM in DMSO , 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, CAS No.1802929-43-6, 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

CAS: 1802929-43-6 Cat. No.: P422209 Fórmula: C₂₆H₃₀Cl₂N₆O₄ Peso molecular: 561.46 PubChem CID: 118295624

GRADE & PURITY Moligand™, 10mM in DMSO

Synonyms

CCG-270053 | C92492 | NSC801089 | NSC-801089 | s8578 | AC-35543 | GTPL9788 | HY-101768 | EX-A2927 | PRN 1371 [WHO-DD] | 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 | BDBM28698

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Descripción general

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 

Specifications

Sinónimos

CCG-270053 | C92492 | NSC801089 | NSC-801089 | s8578 | AC-35543 | GTPL9788 | HY-101768 | EX-A2927 | PRN 1371 [WHO-DD] | 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 | BDBM28698

Especificaciones y pureza

Moligand™, 10mM in DMSO

Mecanismos bioquímicos y fisiológicos

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.

Condiciones de almacenamiento de almacenamiento

Store at -80°C

Enviado en

Dry ice packs + Cold packs

Este producto requiere envío en cadena de frío. Los servicios terrestres y otros servicios económicos no están disponibles.

Grado

Moligand™

Tipo de acción

INHIBITOR

Mecanismo de acción

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

Propiedades del producto

• ALogP: 3.438
• Recuento HBD: 1
• Enlace rotable: 9

Nombres e identificadores

• Pubchem Sid: 528766694
• Sonrisas canónicas: CNC1=NC=C2C=C(C(=O)N(C2=N1)CCCN3CCN(CC3)C(=O)C=C)C4=C(C(=CC(=C4Cl)OC)OC)Cl
• 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
• InChIKey: PUIXMSRTTHLNKI-UHFFFAOYSA-N
• 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)
• Isómeros 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
• Peso molecular: 561.46

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Clase Pyridines and derivatives
      • Subclass Phenylpyridines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Clase: Pyridines and derivatives
• Subclass: Phenylpyridines
• Intermediate Tree Nodes: Not available
• Direct Parent: Phenylpyridines
• Alternative Parents: Pyrido[2,3-d]pyrimidines Dimethoxybenzenes Phenoxy compounds Dichlorobenzenes Anisoles Secondary alkylarylamines Pyridinones N-alkylpiperazines Aminopyrimidines and derivatives Alkyl aryl ethers Aryl chlorides Tertiary carboxylic acid amides Heteroaromatic compounds Acrylic acids and derivatives Trialkylamines Lactams Amino acids and derivatives Azacyclic compounds Organopnictogen compounds Organochlorides Organic oxides Hydrocarbon derivatives Carbonyl compounds
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: 3-phenylpyridine - Pyrido[2,3-d]pyrimidine - M-dimethoxybenzene - Dimethoxybenzene - Pyridopyrimidine - Phenoxy compound - Methoxybenzene - Phenol ether - 1,3-dichlorobenzene - Anisole - N-alkylpiperazine - Secondary aliphatic/aromatic amine - Pyridinone - Halobenzene - Chlorobenzene - Aminopyrimidine - Alkyl aryl ether - Benzenoid - Pyrimidine - Piperazine - 1,4-diazinane - Monocyclic benzene moiety - Aryl halide - Aryl chloride - Acrylic acid or derivatives - Heteroaromatic compound - Tertiary carboxylic acid amide - Tertiary aliphatic amine - Tertiary amine - Lactam - Carboxamide group - Amino acid or derivatives - Azacycle - Secondary amine - Ether - Carboxylic acid derivative - Organic nitrogen compound - Organic oxygen compound - Organopnictogen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Organonitrogen compound - Organochloride - Organohalogen compound - Carbonyl group - Amine - Aromatic heteropolycyclic compound
• Descripción: This compound belongs to the class of organic compounds known as phenylpyridines. These are polycyclic aromatic compounds containing a benzene ring linked to a pyridine ring through a CC or CN bond.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Objetivos asociados (humanos)

CSF1R Tclin Macrophage colony-stimulating factor 1 receptor (1 Activities)

Discover Target: CSF1R

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

FGFR1 Tclin Fibroblast growth factor receptor 1 (5 Activities)

Discover Target: FGFR1

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

FGFR2 Tclin Fibroblast growth factor receptor 2 (3 Activities)

Discover Target: FGFR2

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

FGFR4 Tclin Fibroblast growth factor receptor 4 (2 Activities)

Discover Target: FGFR4

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

FGFR3 Tclin Fibroblast growth factor receptor 3 (3 Activities)

Discover Target: FGFR3

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

KCNH2 Tclin HERG (29587 Activities)

Discover Target: KCNH2

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

FGFR2 Tclin Fibroblast growth factor receptor 2 (3405 Activities)

Discover Target: FGFR2

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

FGFR1 Tclin Fibroblast growth factor receptor 1 (9149 Activities)

Discover Target: FGFR1

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

JAK3 Tclin Tyrosine-protein kinase JAK3 (8349 Activities)

Discover Target: JAK3

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

KDR Tclin Vascular endothelial growth factor receptor 2 (20924 Activities)

Discover Target: KDR

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

BLK Tchem Tyrosine-protein kinase BLK (2498 Activities)

Discover Target: BLK

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

FLT4 Tclin Vascular endothelial growth factor receptor 3 (3216 Activities)

Discover Target: FLT4

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

LYN Tclin Tyrosine-protein kinase Lyn (4251 Activities)

Discover Target: LYN

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

CSF1R Tclin Macrophage colony stimulating factor receptor (5179 Activities)

Discover Target: CSF1R

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

BMX Tchem Tyrosine-protein kinase BMX (1995 Activities)

Discover Target: BMX

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Homo sapiens (32628 Activities)

Explore this target

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

SNU-16 (476 Activities)

Explore this target

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

HepG2 (196354 Activities)

Explore this target

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Liver (3974 Activities)

Explore this target

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

EIF2AK3 Tchem Eukaryotic translation initiation factor 2-alpha kinase 3 (635 Activities)

Discover Target: EIF2AK3

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

TAOK2 Tchem Serine/threonine-protein kinase TAO2 (964 Activities)

Discover Target: TAOK2

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Objetivos asociados (no humanos)

Fgfr4 Fibroblast growth factor receptor 4 (138 Activities)

Discover Target: Fgfr4

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Fgfr3 Fibroblast growth factor receptor 3 (21 Activities)

Discover Target: Fgfr3

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Canis familiaris (36305 Activities)

Explore this target

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Mus musculus (284745 Activities)

Explore this target

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Rattus norvegicus (775804 Activities)

Explore this target

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Cynomolgus monkey (4946 Activities)

Explore this target

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

rep Replicase polyprotein 1ab (378 Activities)

Discover Target: rep

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Blood (6 Activities)

Explore this target

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Plasma (328 Activities)

Explore this target

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Mecanismos de acción

Propiedades químicas y físicas

• DMSO (mg/ml) Solubilidad máxima: 100
• DMSO (mM) Solubilidad máxima: 178.107078
• Agua (mg/ml) Solubilidad máxima: ＜1
• Peso molecular: 561.500 g/mol
• XLogP3: 3.500
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 9
• Exact Mass: 560.171 Da
• Monoisotopic Mass: 560.171 Da
• Topological Polar Surface Area: 100.000 Ų
• Heavy Atom Count: 38
• Formal Charge: 0
• Complexity: 870.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1