Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMNAFG1)

• Drug Name: Olomoucine Drug Info
• Synonyms: olomoucine; 101622-51-9; 4erk; UNII-6A839B2HYS; 2-(2-Hydroxyethylamino)-6-benzylamino-9-methylpurine; 6A839B2HYS; CHEMBL280074; 2-{[6-(benzylamino)-9-methyl-9h-purin-2-yl]amino}ethanol; 6-Benzylamino-2-(2-hydroxyethylamino)-9-methylpurine; 6-(Benzylamino)-2-(2-hydroxyethylamino)-9-methylpurine; Ethanol,2-[[9-methyl-6-[(phenylmethyl)amino]-9H-purin-2-yl]amino]-; OLO; 2-(Hydroxyethylamino)-6-benzylamino-9-methylpurine; 6-Benylamino-2-(2-hydroxyethylamino)-9-methylpurine
• Cross-matching ID:
  PubChem CID: 4592
  ChEBI ID: CHEBI:44661
  CAS Number: CAS 101622-51-9
  TTD Drug ID: DMNAFG1

Molecule-Related Drug Atlas

Drug(s) Targeting Cyclin-dependent kinase 5 (CDK5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
KENPAULLONE	DMAGVXW	Discovery agent	N.A.	Patented	[4]
Roscovitine derivative 1	DMD1G3Z	N. A.	N. A.	Patented	[5]
Tricyclic benzimidazole derivative 1	DM5SD9E	N. A.	N. A.	Patented	[5]
4-(thiazol-5-yl)-pyrimidine derivative 2	DMMQFCN	N. A.	N. A.	Patented	[5]
Pyrazolo[1,5-a]-1,3,5-triazine derivative 1	DMOK7CW	N. A.	N. A.	Patented	[5]
Naphthyridine and isoquinoline derivative 1	DMTGIP7	N. A.	N. A.	Patented	[5]
PMID26161698-Compound-18	DM6JVR5	N. A.	N. A.	Patented	[5]
Flavonoid derivative 7	DM6A9UR	N. A.	N. A.	Patented	[5]
L-751250	DMOERXK	Obesity	5B81	Preclinical	[2]
aloisine A	DM5U1LN	Discovery agent	N.A.	Investigative	[6]

Drug(s) Targeting Cyclin-dependent kinase 1 (CDK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
R-roscovitine	DMSH108	Non-small-cell lung cancer	2C25.Y	Phase 2	[7]
Ro 31-7453	DM83QCL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[8]
P276-00	DM9DJL2	Mantle cell lymphoma	2A85.5	Phase 2	[7]
P-276	DMMJUHD	Breast cancer	2C60-2C65	Phase 2	[9]
RGB-286638	DMEGOQP	Haematological malignancy	2B33.Y	Phase 1	[10]
AG-024322	DMY4WVK	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
PHA-793887	DM2Y4FG	Solid tumour/cancer	2A00-2F9Z	Phase 1	[11]
Oxazolyl methylthiothiazole derivative 1	DMZM6FW	N. A.	N. A.	Patented	[5]
PMID25991433-Compound-A1	DM89LF0	N. A.	N. A.	Patented	[12]
KENPAULLONE	DMAGVXW	Discovery agent	N.A.	Patented	[13]

Drug(s) Targeting Cyclin-dependent kinase 2 (CDK2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
R-roscovitine	DMSH108	Non-small-cell lung cancer	2C25.Y	Phase 2	[7]
Ro 31-7453	DM83QCL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[8]
PHA848125	DMS2Q9G	Thymic cancer	2C27	Phase 2	[14]
TG02	DMZFIGQ	Anaplastic astrocytoma	2A00.0	Phase 1/2	[15]
NUV-422	DMQJQNT	Malignant glioma	2A00.0	Phase 1/2	[16]
RGB-286638	DMEGOQP	Haematological malignancy	2B33.Y	Phase 1	[10]
FN-1501	DM7BMD6	Solid tumour/cancer	2A00-2F9Z	Phase 1	[17]
AG-024322	DMY4WVK	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
PHA-793887	DM2Y4FG	Solid tumour/cancer	2A00-2F9Z	Phase 1	[11]
SNS-032	DMEITAS	Solid tumour/cancer	2A00-2F9Z	Phase 1	[18]

Drug(s) Affected By Retinoblastoma-associated protein (RB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Indomethacin	DMSC4A7	Bursitis		Approved	[19]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[20]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[21]
Talazoparib	DM1KS78	Breast cancer	2C60-2C65	Approved	[22]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[23]
Trametinib	DM2JGQ3	Melanoma	2C30	Approved	[24]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[25]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[26]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[27]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[28]

Drug(s) Affected By Transcription factor Sp1 (SP1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fructose	DM43AN2	Vomiting	MD90	Approved	[29]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[30]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[31]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[32]
Penicillamine	DM40EF6	Cystinuria	5C60.2	Approved	[33]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[34]
Acetic Acid, Glacial	DM4SJ5Y	infection in the ear canal	AA0Y	Approved	[35]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[30]
Thalidomide	DM70BU5	Adult T-cell leukemia/lymphoma		Approved	[36]
Plicamycin	DM7C8YV	Hypercalcaemia	5B91.0	Approved	[37]

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	Binder	[1]
Cyclin-dependent kinase 2 (CDK2)	TT7HF4W	CDK2_HUMAN	Inhibitor	[2]
Cyclin-dependent kinase 5 (CDK5)	TTL4Q97	CDK5_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Gene/Protein Processing	[3]
Transcription factor Sp1 (SP1)	OTISPT4X	SP1_HUMAN	Gene/Protein Processing	[3]

References

• [1] Antiproliferative activity of olomoucine II, a novel 2,6,9-trisubstituted purine cyclin-dependent kinase inhibitor. Cell Mol Life Sci. 2005 Aug;62(15):1763-71.
• [2] Pharmacological inhibitors of cyclin-dependent kinases. Trends Pharmacol Sci. 2002 Sep;23(9):417-25.
• [3] The expression of retinoblastoma and Sp1 is increased by low concentrations of cyclin-dependent kinase inhibitors. Eur J Biochem. 2003 Dec;270(24):4809-22. doi: 10.1046/j.1432-1033.2003.03874.x.
• [4] 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta. Bioorg Med Chem Lett. 2004 Jan 19;14(2):413-6.
• [5] Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.
• [6] Aloisines, a new family of CDK/GSK-3 inhibitors. SAR study, crystal structure in complex with CDK2, enzyme selectivity, and cellular effects. J Med Chem. 2003 Jan 16;46(2):222-36.
• [7] Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
• [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] 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.
• [10] 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.
• [11] 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.
• [12] c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.
• [13] 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.
• [14] 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.
• [15] Preclinical metabolism and pharmacokinetics of SB1317 (TG02), a potent CDK/JAK2/FLT3 inhibitor. Drug Metab Lett. 2012 Mar;6(1):33-42.
• [16] ClinicalTrials.gov (NCT04541225) Phase 1/2 Dose Escalation, Safety, Pharmacokinetics, and Efficacy Study of NUV-422 in Adults With Recurrent or Refractory High-grade Gliomas and Solid Tumors. U.S.National Institutes of Health.
• [17] 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.
• [18] Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood. 2009 May 7;113(19):4637-45.
• [19] Indomethacin inhibits cell growth of medullary thyroid carcinoma by reducing cell cycle progression into S phase. Exp Biol Med (Maywood). 2008 Nov;233(11):1433-40. doi: 10.3181/0804-RM-127. Epub 2008 Sep 12.
• [20] Therapeutically activating RB: reestablishing cell cycle control in endocrine therapy-resistant breast cancer. Endocr Relat Cancer. 2011 Apr 28;18(3):333-45. doi: 10.1530/ERC-10-0262. Print 2011 Jun.
• [21] Effects and mechanisms of betulinic acid on improving EGFR TKI-resistance of lung cancer cells. Environ Toxicol. 2018 Nov;33(11):1153-1159.
• [22] BMN 673 (talazoparib): A potent PARP inhibitor for triple negative breast cancer with different genetic profile. J Biochem Mol Toxicol. 2019 May;33(5):e22286. doi: 10.1002/jbt.22286. Epub 2019 Jan 23.
• [23] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [24] Combination small molecule MEK and PI3K inhibition enhances uveal melanoma cell death in a mutant GNAQ- and GNA11-dependent manner. Clin Cancer Res. 2012 Aug 15;18(16):4345-55. doi: 10.1158/1078-0432.CCR-11-3227. Epub 2012 Jun 25.
• [25] Sulindac induces specific degradation of the HPV oncoprotein E7 and causes growth arrest and apoptosis in cervical carcinoma cells. Cancer Lett. 2007 Jan 8;245(1-2):103-11. doi: 10.1016/j.canlet.2005.12.034. Epub 2006 Feb 20.
• [26] Melanoma coordinates general and cell-specific mechanisms to promote methotrexate resistance. Exp Cell Res. 2012 Jun 10;318(10):1146-59.
• [27] HMG-CoA reductase inhibitor simvastatin inhibits cell cycle progression at the G1/S checkpoint in immortalized lymphocytes from Alzheimer's disease patients independently of cholesterol-lowering effects. J Pharmacol Exp Ther. 2008 Jan;324(1):352-9. doi: 10.1124/jpet.107.128959. Epub 2007 Oct 10.
• [28] Inhibition of prostate cancer cell colony formation by the flavonoid quercetin correlates with modulation of specific regulatory genes. Clin Diagn Lab Immunol. 2004 Jan;11(1):63-9. doi: 10.1128/cdli.11.1.63-69.2004.
• [29] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [30] Arsenic trioxide downregulates specificity protein (Sp) transcription factors and inhibits bladder cancer cell and tumor growth. Exp Cell Res. 2010 Aug 1;316(13):2174-88. doi: 10.1016/j.yexcr.2010.04.027. Epub 2010 May 8.
• [31] Quercetin augments TRAIL-induced apoptotic death: involvement of the ERK signal transduction pathway. Biochem Pharmacol. 2008 May 15;75(10):1946-58. doi: 10.1016/j.bcp.2008.02.016. Epub 2008 Mar 10.
• [32] Peroxisome proliferator-activated receptor-gamma ligands suppress fibronectin gene expression in human lung carcinoma cells: involvement of both CRE and Sp1. Am J Physiol Lung Cell Mol Physiol. 2005 Sep;289(3):L419-28. doi: 10.1152/ajplung.00002.2005. Epub 2005 May 20.
• [33] Mechanistic basis for overcoming platinum resistance using copper chelating agents. Mol Cancer Ther. 2012 Nov;11(11):2483-94. doi: 10.1158/1535-7163.MCT-12-0580. Epub 2012 Aug 21.
• [34] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [35] Regulation of the high-affinity copper transporter (hCtr1) expression by cisplatin and heavy metals. J Biol Inorg Chem. 2014 Jan;19(1):17-27. doi: 10.1007/s00775-013-1051-z. Epub 2013 Oct 17.
• [36] Thalidomide and a thalidomide analogue inhibit endothelial cell proliferation in vitro. J Neurooncol. 1999 Jun;43(2):109-14. doi: 10.1023/a:1006202700039.
• [37] The activity of a novel mithramycin analog is related to its binding to DNA, cellular accumulation, and inhibition of Sp1-driven gene transcription. Chem Biol Interact. 2014 Aug 5;219:123-32. doi: 10.1016/j.cbi.2014.05.019. Epub 2014 Jun 4.