General Information of Drug (ID: DMV2DIW)

Drug Name
BAY 10-00394
Synonyms roniciclib; BAY 1000394; BAY 10-00394; KB-145902; 1223498-69-8; Tube010; SCHEMBL875845; GTPL7874
Indication
Disease Entry ICD 11 Status REF
Small-cell lung cancer 2C25.Y Discontinued in Phase 2 [1], [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 430.4
Topological Polar Surface Area (xlogp) 4.5
Rotatable Bond Count (rotbonds) 7
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 10
Chemical Identifiers
Formula
C18H21F3N4O3S
IUPAC Name
(2R,3R)-3-[2-[4-(cyclopropylsulfonimidoyl)anilino]-5-(trifluoromethyl)pyrimidin-4-yl]oxybutan-2-ol
Canonical SMILES
C[C@H]([C@@H](C)OC1=NC(=NC=C1C(F)(F)F)NC2=CC=C(C=C2)S(=N)(=O)C3CC3)O
InChI
InChI=1S/C18H21F3N4O3S/c1-10(26)11(2)28-16-15(18(19,20)21)9-23-17(25-16)24-12-3-5-13(6-4-12)29(22,27)14-7-8-14/h3-6,9-11,14,22,26H,7-8H2,1-2H3,(H,23,24,25)/t10-,11-,29?/m1/s1
InChIKey
UELYDGOOJPRWGF-MFOHZAOFSA-N
Cross-matching ID
PubChem CID
45380979
TTD ID
D0NV9O

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Cyclin-dependent kinase 1 (CDK1) TTH6V3D CDK1_HUMAN Inhibitor [3]
Cyclin-dependent kinase 2 (CDK2) TT7HF4W CDK2_HUMAN Inhibitor [3]
Cyclin-dependent kinase 4 (CDK4) TT0PG8F CDK4_HUMAN Inhibitor [4]
Cyclin-dependent kinase 9 (CDK9) TT1LVF2 CDK9_HUMAN Inhibitor [3]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Small-cell lung cancer
ICD Disease Classification 2C25.Y
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Cyclin-dependent kinase 1 (CDK1) DTT CDK1 5.27E-108 1.97 3.12
Cyclin-dependent kinase 2 (CDK2) DTT CDK2 2.28E-06 0.12 0.19
Cyclin-dependent kinase 9 (CDK9) DTT CDK9 4.38E-01 -0.04 -0.1
Cyclin-dependent kinase 4 (CDK4) DTT CDK4 3.30E-72 0.65 2.39
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: 7874).
2 BAY 1000394, a novel cyclin-dependent kinase inhibitor, with potent antitumor activity in mono- and in combination treatment upon oral application. Mol Cancer Ther. 2012 Oct;11(10):2265-73.
3 National Cancer Institute Drug Dictionary (drug id 770319).
4 Liposarcoma: molecular genetics and therapeutics. Sarcoma. 2011;2011:483154.
5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
6 Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
7 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.
8 Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood. 2009 May 7;113(19):4637-45.
9 Clinical pipeline report, company report or official report of BioTheryX.
10 Clinical pipeline report, company report or official report of Sumitomo Dainippon Pharma.
11 Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.
12 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.
13 P276-00, a novel cyclin-dependent inhibitor induces G1-G2 arrest, shows antitumor activity on cisplatin-resistant cells and significant in vivo efficacy in tumor models. Mol Cancer Ther. 2007 Mar;6(3):926-34.
14 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.
15 c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.
16 Discovery of novel CDK1 inhibitors by combining pharmacophore modeling, QSAR analysis and in silico screening followed by in vitro bioassay. Eur J Med Chem. 2010 Sep;45(9):4316-30.
17 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.
18 Preclinical metabolism and pharmacokinetics of SB1317 (TG02), a potent CDK/JAK2/FLT3 inhibitor. Drug Metab Lett. 2012 Mar;6(1):33-42.
19 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.
20 Agreement signed with Prostagenics to develop prostate cancer treatment. Innovate Oncology, Inc. 2005.
21 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
22 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2017
23 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
24 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
25 Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res. 2013 Nov 15;19(22):6173-82.