Details of the Drug

General Information of Drug (ID: DMKTB5U)

Drug Name
PYRAZOLOPYRIDAZINE 1
Synonyms
PYRAZOLOPYRIDAZINE 1; 551920-54-8; GW810576X; n-(3-methoxyphenyl)-4-pyrazolo[1,5-b]pyridazin-3-yl-2-pyrimidinamine; pyrazolo[1,5-b]pyridazine deriv. 19; AC1O6ZIQ; CHEMBL187081; BDBM8128; SCHEMBL4489357; CTK1F7320; DTXSID60424889; HMS3305F24; HMS3303K24; ZINC13582569; NCGC00242229-01; DA-42106; FT-0707969; AB01092291-01; 2-Pyrimidinamine, N-(3-methoxyphenyl)-4-pyrazolo[1,5-b]pyridazin-3-yl-; N-(3-methoxyphenyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine
Indication
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 318.33
Topological Polar Surface Area (xlogp) 2.4
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 6
Chemical Identifiers
Formula
C17H14N6O
IUPAC Name
N-(3-methoxyphenyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine
Canonical SMILES
COC1=CC=CC(=C1)NC2=NC=CC(=N2)C3=C4C=CC=NN4N=C3
InChI
InChI=1S/C17H14N6O/c1-24-13-5-2-4-12(10-13)21-17-18-9-7-15(22-17)14-11-20-23-16(14)6-3-8-19-23/h2-11H,1H3,(H,18,21,22)
InChIKey
GBNWWXHUOVAUHT-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
6539361
CAS Number
551920-54-8
TTD ID
D02DLC

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Cyclin-dependent kinase 2 (CDK2) TT7HF4W CDK2_HUMAN Inhibitor [1]
Cyclin-dependent kinase 4 (CDK4) TT0PG8F CDK4_HUMAN Inhibitor [1]
Glycogen synthase kinase-3 beta (GSK-3B) TTRSMW9 GSK3B_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 Discovery agent
ICD Disease Classification N.A.
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Glycogen synthase kinase-3 beta (GSK-3B) DTT GSK3B 1.26E-01 -0.23 -0.77
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 N-Phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amines as potent and selective inhibitors of glycogen synthase kinase 3 with good cellular effi... J Med Chem. 2004 Sep 9;47(19):4716-30.
2 Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
3 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.
4 Identification of N,1,4,4-tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (PHA-848125), a potent, orally available cyclin dependent kinase inhibitor. J Med Chem. 2009 Aug 27;52(16):5152-63.
5 Preclinical metabolism and pharmacokinetics of SB1317 (TG02), a potent CDK/JAK2/FLT3 inhibitor. Drug Metab Lett. 2012 Mar;6(1):33-42.
6 Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs. Leukemia. 2013 Dec;27(12):2366-75.
7 Discovery of 4-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-N-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-pyrazole-3-carboxamide (FN-1501), an FLT3- and CDK-Kinase Inhibitor with Potentially High Efficiency against Acute Myelocytic Leukemia. J Med Chem. 2018 Feb 22;61(4):1499-1518.
8 A first in man, phase I dose-escalation study of PHA-793887, an inhibitor of multiple cyclin-dependent kinases (CDK2, 1 and 4) reveals unexpected h... Cell Cycle. 2011 Mar 15;10(6):963-70.
9 Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood. 2009 May 7;113(19):4637-45.
10 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
11 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
12 Glycogen synthase kinase 3 (GSK-3) inhibitors: a patent update (2014-2015).Expert Opin Ther Pat. 2017 Jun;27(6):657-666.
13 The GSK3 kinase inhibitor lithium produces unexpected hyperphosphorylation of -catenin, a GSK3 substrate, in human glioblastoma cells. Biol Open. 2018 Jan 26;7(1):bio030874.
14 Evidence for irreversible inhibition of glycogen synthase kinase-3beta by tideglusib. J Biol Chem. 2012 Jan 6;287(2):893-904.
15 9-ING-41, a small molecule inhibitor of GSK-3beta, potentiates the effects of anticancer therapeutics in bladder cancer. Sci Rep. 2019 Dec 27;9(1):19977.
16 Company report (Neurim Pharmaceuticals)
17 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta. Bioorg Med Chem Lett. 2004 Jan 19;14(2):413-6.
18 Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo. Diabetes. 2003 Mar;52(3):588-95.
19 Identification of novel scaffold of benzothiazepinones as non-ATP competitive glycogen synthase kinase-3beta inhibitors through virtual screening. Bioorg Med Chem Lett. 2012 Dec 1;22(23):7232-6.
20 Fragment and knowledge-based design of selective GSK-3beta inhibitors using virtual screening models. Eur J Med Chem. 2009 Jun;44(6):2361-71.
21 Agreement signed with Prostagenics to develop prostate cancer treatment. Innovate Oncology, Inc. 2005.
22 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
23 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2017
24 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
25 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
26 Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res. 2013 Nov 15;19(22):6173-82.
27 Liposarcoma: molecular genetics and therapeutics. Sarcoma. 2011;2011:483154.