Details of the Drug

General Information of Drug (ID: DMEGOQP)

Drug Name
RGB-286638
Synonyms
GPC-286199; RGB-286199; RGB-344064; Non-selective CDK inhibitors, Agennix; Non-selective CDK inhibitors, GPC Biotech; Non-selective cyclin dependent kinase inhibitors, Agennix; Non-selective cyclin dependent kinase inhibitors, GPC Biotech
Indication
Disease Entry ICD 11 Status REF
Haematological malignancy 2B33.Y Phase 1 [1], [2]
Drug Type
Small molecular drug
Structure
3D MOL is unavailable 2D MOL
#Ro5 Violations (Lipinski):
1		 Molecular Weight 618.6
Topological Polar Surface Area Not Available
Rotatable Bond Count 8
Hydrogen Bond Donor Count 5
Hydrogen Bond Acceptor Count 8
Chemical Identifiers
Formula
C29H37Cl2N7O4
IUPAC Name
1-[3-[4-[[4-(2-methoxyethyl)piperazin-1-yl]methyl]phenyl]-4-oxo-1H-indeno[1,2-c]pyrazol-5-yl]-3-morpholin-4-ylurea;dihydrochloride
Canonical SMILES
COCCN1CCN(CC1)CC2=CC=C(C=C2)C3=NNC4=C3C(=O)C5=C4C=CC=C5NC(=O)NN6CCOCC6.Cl.Cl
InChI
InChI=1S/C29H35N7O4.2ClH/c1-39-16-13-34-9-11-35(12-10-34)19-20-5-7-21(8-6-20)26-25-27(32-31-26)22-3-2-4-23(24(22)28(25)37)30-29(38)33-36-14-17-40-18-15-36;;/h2-8H,9-19H2,1H3,(H,31,32)(H2,30,33,38);2*1H
InChIKey
WJVMGQMXUBAAPL-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
11285001
CAS Number
784210-87-3
TTD ID
D03DKV

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 3 (CDK3) TTMYWL7 CDK3_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 Haematological malignancy
ICD Disease Classification 2B33.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: 7744).
2 ClinicalTrials.gov (NCT01168882) Safety and Tolerability of RGB-286638 in Patients With Selected, Relapsed or Refractory Hematological Malignancies. U.S. National Institutes of Health.
3 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.
4 Liposarcoma: molecular genetics and therapeutics. Sarcoma. 2011;2011:483154.
5 Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.
6 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
7 Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
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 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 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.
13 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.
14 c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.
15 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.
16 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.
17 Preclinical metabolism and pharmacokinetics of SB1317 (TG02), a potent CDK/JAK2/FLT3 inhibitor. Drug Metab Lett. 2012 Mar;6(1):33-42.
18 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.
19 AZD5438, an inhibitor of Cdk1, 2, and 9, enhances the radiosensitivity of non-small cell lung carcinoma cells.Int J Radiat Oncol Biol Phys.2012 Nov 15;84(4):e507-14.
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.