FS-694

ID: ALA2316207

Max Phase: Preclinical

Molecular Formula: C35H33FN4O4

Molecular Weight: 592.67

Molecule Type: Small molecule

Associated Items:

Representations

Canonical SMILES:  O=C(NCCN1CCOCC1)c1ccc2c(c1)C(=O)c1ccc(Nc3ccc(F)c(NC(=O)c4ccccc4)c3)cc1CC2

Standard InChI:  InChI=1S/C35H33FN4O4/c36-31-13-11-28(22-32(31)39-35(43)24-4-2-1-3-5-24)38-27-10-12-29-25(20-27)8-6-23-7-9-26(21-30(23)33(29)41)34(42)37-14-15-40-16-18-44-19-17-40/h1-5,7,9-13,20-22,38H,6,8,14-19H2,(H,37,42)(H,39,43)

Standard InChI Key:  JWZSSEWMVYKYKW-UHFFFAOYSA-N

Associated Targets(Human)

Casein kinase I epsilon 1412 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

MAP kinase p38 beta 2785 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

MAP kinase p38 alpha 12866 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

HEK-293T 167025 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

U2OS 164939 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Fibroblast 163371 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Heat shock protein beta-1 172 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

TNF-alpha 1897 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Tyrosine-protein kinase ABL 18331 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Serine/threonine-protein kinase Aurora-A 10240 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Bromodomain-containing protein 4 13122 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Peregrin 2217 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Cyclin-dependent kinase 2 9050 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Casein kinase I delta 4546 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Fibroblast growth factor receptor 3 7811 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Glycogen synthase kinase-3 beta 11785 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

MAP kinase ERK2 25055 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Transcription intermediary factor 1-alpha 2087 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Serine/threonine-protein kinase Aurora-B 6805 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Casein kinase I isoform gamma-3 2408 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

MAP kinase p38 gamma 2776 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Associated Targets(non-human)

Liver 4264 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Molecule Features

Natural Product: NoOral: NoChemical Probe: YesParenteral: No
Molecule Type: Small moleculeTopical: NoFirst In Class: NoBlack Box: No
Chirality: NoAvailability: NoProdrug: No

Drug Indications

MESH IDMESH Heading EFO IDsEFO TermsMax Phase for IndicationReferences

Mechanisms of Action

Mechanism of ActionAction Typetarget IDTarget NameTarget TypeTarget OrganismBinding Site NameReferences

Properties

Molecular Weight: 592.67Molecular Weight (Monoisotopic): 592.2486AlogP: 5.21#Rotatable Bonds: 8
Polar Surface Area: 99.77Molecular Species: NEUTRALHBA: 6HBD: 3
#RO5 Violations: 2HBA (Lipinski): 8HBD (Lipinski): 3#RO5 Violations (Lipinski): 2
CX Acidic pKa: CX Basic pKa: 5.28CX LogP: 5.54CX LogD: 5.54
Aromatic Rings: 4Heavy Atoms: 44QED Weighted: 0.26Np Likeness Score: -1.39

References

1. Fischer S, Wentsch HK, Mayer-Wrangowski SC, Zimmermann M, Bauer SM, Storch K, Niess R, Koeberle SC, Grütter C, Boeckler FM, Rauh D, Laufer SA..  (2013)  Dibenzosuberones as p38 mitogen-activated protein kinase inhibitors with low ATP competitiveness and outstanding whole blood activity.,  56  (1): [PMID:23270382] [10.1021/jm301539x]
2. Walter NM, Wentsch HK, Bührmann M, Bauer SM, Döring E, Mayer-Wrangowski S, Sievers-Engler A, Willemsen-Seegers N, Zaman G, Buijsman R, Lämmerhofer M, Rauh D, Laufer SA..  (2017)  Design, Synthesis, and Biological Evaluation of Novel Type I1/2 p38α MAP Kinase Inhibitors with Excellent Selectivity, High Potency, and Prolonged Target Residence Time by Interfering with the R-Spine.,  60  (19): [PMID:28834431] [10.1021/acs.jmedchem.7b00745]
3. SGC Frankfurt.  (2021)  Data for DCP probe FS-694,  [10.6019/CHEMBL4507314]
4. Pedreira JGB, Nahidino P, Kudolo M, Pantsar T, Berger BT, Forster M, Knapp S, Laufer S, Barreiro EJ..  (2020)  Bioisosteric Replacement of Arylamide-Linked Spine Residues with N-Acylhydrazones and Selenophenes as a Design Strategy to Novel Dibenzosuberone Derivatives as Type I 1/2 p38α MAP Kinase Inhibitors.,  63  (13): [PMID:32462866] [10.1021/acs.jmedchem.0c00508]
5.  (2021)  EUbOPEN Chemogenomics Library wave 1,  [10.6019/CHEMBL4689842]
6. EUbOPEN.  (2022)  EUbOPEN Chemogenomics Library wave 2 - DSF,  [10.6019/CHEMBL5060014]
7. Carrillo García C, Becker C, Forster M, Lohmann S, Freitag P, Laufer S, Sievers S, Fleischmann BK, Hesse M, Schade D..  (2022)  High-Throughput Screening Platform in Postnatal Heart Cells and Chemical Probe Toolbox to Assess Cardiomyocyte Proliferation.,  65  (2.0): [PMID:34818008] [10.1021/acs.jmedchem.1c01173]
8. EUbOPEN.  (2023)  Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomics Library wave 3,  [10.6019/CHEMBL5209897]
9. EUbOPEN.  (2023)  Affinity On-target Cellular Literature for EUbOPEN Chemogenomics Library wave 3,  [10.6019/CHEMBL5210121]
10. EUbOPEN.  (2023)  Affinity Biochemical Literature for EUbOPEN Chemogenomics Library wave 3,  [10.6019/CHEMBL5210307]
11. EUbOPEN.  (2023)  Selectivity Literature for EUbOPEN Chemogenomics Library wave 3,  [10.6019/CHEMBL5212743]