Details of the Drug

General Information of Drug (ID: DMPHSU8)

Drug Name
ACTB-1003
Synonyms Multi-mode kinase inhibitor (oral, cancer), ACT Biotech; Multi-mode kinase inhibitor (oral, cancer), Bayer
Indication
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Investigative [1]
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 2 Molecular Weight (mw) 591.5
Topological Polar Surface Area (xlogp) 2.5
Rotatable Bond Count (rotbonds) 7
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 12
Chemical Identifiers
Formula
C27H26F5N7O3
IUPAC Name
1-[4-[4-amino-6-(methoxymethyl)-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-fluorophenyl]-3-[2-fluoro-5-(trifluoromethyl)phenyl]urea
Canonical SMILES
COCC1=C(N2C(=C1C3=CC(=C(C=C3)NC(=O)NC4=C(C=CC(=C4)C(F)(F)F)F)F)C(=NC=N2)N)CN5CCOCC5
InChI
InChI=1S/C27H26F5N7O3/c1-41-13-17-22(12-38-6-8-42-9-7-38)39-24(25(33)34-14-35-39)23(17)15-2-5-20(19(29)10-15)36-26(40)37-21-11-16(27(30,31)32)3-4-18(21)28/h2-5,10-11,14H,6-9,12-13H2,1H3,(H2,33,34,35)(H2,36,37,40)
InChIKey
GZPJCJKUZPUFAL-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
23653175
CAS Number
939805-30-8
TTD ID
D0R6OM

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Fibroblast growth factor receptor 1 (FGFR1) TTRLW2X FGFR1_HUMAN Inhibitor [2]
Fibroblast growth factor receptor 2 (FGFR2) TTGJVQM FGFR2_HUMAN Inhibitor [3]
Fibroblast growth factor receptor 3 (FGFR3) TTST7KB FGFR3_HUMAN Inhibitor [4]
Fibroblast growth factor receptor 4 (FGFR4) TT5BR7T FGFR4_HUMAN Inhibitor [5]
Ribosomal protein S6 kinase beta-1 (S6K1) TTG0U4H KS6B1_HUMAN Inhibitor [1]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Solid tumour/cancer
ICD Disease Classification 2A00-2F9Z
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Fibroblast growth factor receptor 3 (FGFR3) DTT FGFR3 5.83E-03 0.08 0.1
Fibroblast growth factor receptor 1 (FGFR1) DTT FGFR1 4.79E-02 -0.03 -0.15
Fibroblast growth factor receptor 2 (FGFR2) DTT FGFR2 4.82E-01 -0.03 -0.2
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1525).
2 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1808).
3 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1809).
4 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1810).
5 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1811).
6 Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
7 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
8 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
9 E-3810 is a potent dual inhibitor of VEGFR and FGFR that exerts antitumor activity in multiple preclinical models. Cancer Res. 2011 Feb 15;71(4):1396-405.
10 Clinical pipeline report, company report or official report of Hutchison Medi Pharma.
11 A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
12 Pharmacological inhibition of fibroblast growth factor (FGF) receptor signaling ameliorates FGF23-mediated hypophosphatemic rickets. J Bone Miner Res. 2013 Apr;28(4):899-911.
13 AZD4547: an orally bioavailable, potent, and selective inhibitor of the fibroblast growth factor receptor tyrosine kinase family. Cancer Res. 2012 Apr 15;72(8):2045-56.
14 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
15 DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.
16 Keratinocyte growth factor. Expert Opin Biol Ther. 2009 Jun;9(6):779-87.
17 Emerging drugs for diabetic foot ulcers. Expert Opin Emerg Drugs. 2006 Nov;11(4):709-24.
18 Company report (Eli Lilly) (drug: LY2874455)
19 MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.
20 National Cancer Institute Drug Dictionary (drug id 751593).
21 Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
22 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
23 In vitro and in vivo characterization of Recifercept, a soluble fibroblast growth factor receptor 3, as treatment for achondroplasia. PLoS One. 2020 Dec 28;15(12):e0244368.
24 Characterization of PF-4708671, a novel and highly specific inhibitor of p70 ribosomal S6 kinase (S6K1). Biochem J. 2010 Oct 15;431(2):245-55.
25 Ribosomal S6 kinase (RSK) modulators: a patent review.Expert Opin Ther Pat. 2016 Sep;26(9):1061-78.
26 Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.
27 4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. J Med Chem. 2006 Nov 2;49(22):6500-9.
28 Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. J Med Chem. 2004 Dec 2;47(25):6239-47.