PF-03715455

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Search structure


Synonyms	Pf-03715455
Status
Molecule Category	UNKNOWN
UNII	0TJ631J0KP
EPA CompTox	DTXSID70147214


Active Pharmaceutical Ingredients Bioactive chemicals	Exact Similarity SubStructure	Threshold (%) >= 70

Structure


InChI Key	VGEXRDWWPSGZDH-UHFFFAOYSA-N
Smiles	CC(C)(C)c1cc(NC(=O)NCc2ccccc2Sc2ccc3nnc(-c4ccccc4SCCO)n3c2)n(-c2ccc(O)c(Cl)c2)n1
InChI	InChI=1S/C35H34ClN7O3S2/c1-35(2,3)30-19-32(43(41-30)23-12-14-27(45)26(36)18-23)38-34(46)37-20-22-8-4-6-10-28(22)48-24-13-15-31-39-40-33(42(31)21-24)25-9-5-7-11-29(25)47-17-16-44/h4-15,18-19,21,44-45H,16-17,20H2,1-3H3,(H2,37,38,46)

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C35H34ClN7O3S2
Molecular Weight	700.29
AlogP	7.8
Hydrogen Bond Acceptor	10.0
Hydrogen Bond Donor	4.0
Number of Rotational Bond	10.0
Polar Surface Area	129.6
Molecular species	NEUTRAL
Aromatic Rings	6.0
Heavy Atoms	48.0

Bioactivity

Mechanism of Action	Action	Reference
MAP kinase p38 alpha inhibitor	INHIBITOR	PubMed Other


Protein: MAP kinase p38 alpha Description: Mitogen-activated protein kinase 14 Organism : Homo sapiens Q16539 ENSG00000112062

Targets	EC50(nM)	IC50(nM)	Kd(nM)	Ki(nM)	Inhibition(%)
Enzyme Kinase Protein Kinase CMGC protein kinase group CMGC protein kinase MAPK family CMGC protein kinase p38 subfamily	-	23	0	-	-
Enzyme Kinase Protein Kinase STE protein kinase group STE protein kinase STE20 family STE protein kinase MSN subfamily	-	6	-	-	-
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase VEGFR family	-	890	-	-	-
Ion channel Voltage-gated ion channel Potassium channels Voltage-gated potassium channel	-	-	-	-	46

Assay Description	Organism	Bioactivity	Reference
Antiinflammatory activity in LPS-stimulated human isolated PBMC assessed as inhibition of TNFalpha production preincubated for 1 hr prior to LPS-challenge by ELISA	Homo sapiens	1.7 nM
Antiinflammatory activity in LPS-stimulated human isolated PBMC assessed as inhibition of TNFalpha preincubated for 40 mins prior to LPS-challenge by ELISA in the presence of 5 uM ATP	Homo sapiens	0.88 nM
Binding affinity to human p38alpha MAPK by surface plasmon resonance method	Homo sapiens	0.001 nM
Inhibition of p38beta MAPK	None	23.0 nM
Inhibition of MINK	None	6.0 nM
Antiinflammatory activity in Sprague-Dawley rat assessed as inhibition of LPS-induced neutrophilia in lungs at 100 ug administered 2 hr prior to LPS-challenge	Rattus norvegicus	50.0 %
Inhibition of human VEGFR1	Homo sapiens	890.0 nM
Inhibition of human ERG at 10 uM by patch clamp assay	Homo sapiens	46.0 %

Cross References

Resources	Reference
ChEMBL	CHEMBL1938400
DrugBank	DB12138
FDA SRS	0TJ631J0KP
Guide to Pharmacology	8179
PDB	YIS
PubChem	11714580
SureChEMBL	SCHEMBL981777

CONTENTS

PREMIER has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 875508. The JU receives support from the EU’s Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA). The views reflect only the authors’ perspective and the JU is not responsible for any use that may be made of the information this manuscript contains.

Elements of the website have been developed under projects PREMIER and the Biocenter Finland Drug Discovery and Chemical Biology network. CSC-IT is thanked for providing computational resources. Content of the website is provided without guarantee for correctness. Data has been collected and integrated from multiple public sources, for the largest: FDA, HUGO Gene Nomenclature Committee, ChEMBL, IUPHAR/BPS guide to pharmacology, Reactome, UniProt, and Ensembl. Credit is given to Ensembl for collecting species images (provided under public domain licences such as Wikimedia and NHGRI).