Details of the Drug

General Information of Drug (ID: DMFO7RP)

Drug Name
KW-2449
Synonyms Tumor antigen-specific mAb (cancer), Kyowa; Tumor antigen-specific monoclonal antibody (cancer), Kyowa Hakko Kirin; Tumor antigen-specific monoclonal antibody (cancer), Kyowa Hakko Kogyo
Indication
Disease Entry ICD 11 Status REF
Acute myeloid leukaemia 2A60 Phase 1 [1], [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 332.4
Topological Polar Surface Area (xlogp) 2.7
Rotatable Bond Count (rotbonds) 3
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 3
Chemical Identifiers
Formula
C20H20N4O
IUPAC Name
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone
Canonical SMILES
C1CN(CCN1)C(=O)C2=CC=C(C=C2)/C=C/C3=NNC4=CC=CC=C43
InChI
InChI=1S/C20H20N4O/c25-20(24-13-11-21-12-14-24)16-8-5-15(6-9-16)7-10-19-17-3-1-2-4-18(17)22-23-19/h1-10,21H,11-14H2,(H,22,23)/b10-7+
InChIKey
YYLKKYCXAOBSRM-JXMROGBWSA-N
Cross-matching ID
PubChem CID
11427553
ChEBI ID
CHEBI:91441
CAS Number
841258-76-2
TTD ID
D00ABO

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 Not Available [2]
Fms-like tyrosine kinase 3 (FLT-3) TTGJCWZ FLT3_HUMAN Not Available [2]
Tyrosine-protein kinase ABL1 (ABL) TT3PJMV ABL1_HUMAN Not Available [2]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Acute myeloid leukaemia
ICD Disease Classification 2A60
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Fibroblast growth factor receptor 1 (FGFR1) DTT FGFR1 4.79E-02 -0.03 -0.15
Fms-like tyrosine kinase 3 (FLT-3) DTT FLT3 2.11E-01 -0.05 -0.16
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. (Ligand id: 5691).
2 KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation. Blood. 2009 Aug 20;114(8):1607-17.
3 Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
4 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
6 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.
7 Clinical pipeline report, company report or official report of Hutchison Medi Pharma.
8 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.
9 Pharmacological inhibition of fibroblast growth factor (FGF) receptor signaling ameliorates FGF23-mediated hypophosphatemic rickets. J Bone Miner Res. 2013 Apr;28(4):899-911.
10 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).
11 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.
12 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
13 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
14 Synthesis and Src kinase inhibitory activity of a series of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-furyl-3-quinolinecarbonitriles. J Med Chem. 2006 Dec 28;49(26):7868-76.
15 Targeted chronic myeloid leukemia therapy: Seeking a cure. Am J Health Syst Pharm. 2007 Dec 15;64(24 Suppl 15):S9-15.
16 Novel dual Src/Abl inhibitors for hematologic and solid malignancies.Expert Opin Investig Drugs.2010 Aug;19(8):931-45.
17 Flumatinib, a selective inhibitor of BCR-ABL/PDGFR/KIT, effectively overcomes drug resistance of certain KIT mutants. Cancer Sci. 2014 Jan;105(1):117-25.
18 Company report (Deciphera Pharmaceuticals: Tumor-Targeted Programs and Indications)
19 Structure-based optimization of pyrazolo[3,4-d]pyrimidines as Abl inhibitors and antiproliferative agents toward human leukemia cell lines. J Med Chem. 2008 Mar 13;51(5):1252-9.
20 Inhibitors of JAK-family kinases: an update on the patent literature 2013-2015, part 1.Expert Opin Ther Pat. 2017 Feb;27(2):127-143.
21 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: 1807).
22 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
23 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
24 Lestaurtinib (CEP701) is a JAK2 inhibitor that suppresses JAK2/STAT5 signaling and the proliferation of primary erythroid cells from patients with ... Blood. 2008 Jun 15;111(12):5663-71.
25 Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.