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

General Information of Drug (ID: DM8LUYM)

• Drug Name: 9-Nitropaullone Drug Info
• Synonyms: Alsterpaullone; alsterpaullone; 237430-03-4; NSC 705701; NSC-705701; CHEMBL50894; MLS002702475; 9-Nitro-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one; 9-nitro-7,12-dihydro-5H-indolo[3,2-d][1]benzazepin-6-one; 9-Nitro-7,12-dihydroindolo-[3,2-d][1]benzazepin-6(5)-one; 9-NITRO-5,12-DIHYDRO-7H-BENZO[2,3]AZEPINO[4,5-B]INDOL-6-ONE; Paullone Analog 1; AC1NMCUD; Kinome_3754; 1q3w; Alsterpaullone derivative, 2; Lopac0_000057; CBiol_001723; GTPL5925; BDBM7262; SCHEMBL2170104; CTK8F0374; ZINC23894; BDBM84528; DTXSID50407444

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 5005498
  ChEBI ID: CHEMBL50894
  CAS Number: CAS 237430-03-4
  TTD Drug ID: DM8LUYM

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	[5]
Roscovitine derivative 1	DMD1G3Z	N. A.	N. A.	Patented	[6]
Tricyclic benzimidazole derivative 1	DM5SD9E	N. A.	N. A.	Patented	[6]
4-(thiazol-5-yl)-pyrimidine derivative 2	DMMQFCN	N. A.	N. A.	Patented	[6]
Pyrazolo[1,5-a]-1,3,5-triazine derivative 1	DMOK7CW	N. A.	N. A.	Patented	[6]
Naphthyridine and isoquinoline derivative 1	DMTGIP7	N. A.	N. A.	Patented	[6]
PMID26161698-Compound-18	DM6JVR5	N. A.	N. A.	Patented	[6]
Flavonoid derivative 7	DM6A9UR	N. A.	N. A.	Patented	[6]
L-751250	DMOERXK	Obesity	5B81	Preclinical	[3]
Olomoucine	DMNAFG1	N. A.	N. A.	Terminated	[3]

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	[6]
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 Tyrosine-protein kinase Lck (LCK)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[19]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[20]
Crizotinib	DM4F29C	Non-small-cell lung cancer	2C25.Y	Approved	[21]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[22]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[23]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[24]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[25]
Enzalutamide	DMGL19D	Prostate cancer	2C82.0	Approved	[26]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[27]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[28]

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	[2]
Cyclin-dependent kinase 2 (CDK2)	TT7HF4W	CDK2_HUMAN	Inhibitor	[3]
Cyclin-dependent kinase 5 (CDK5)	TTL4Q97	CDK5_HUMAN	Inhibitor	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Tyrosine-protein kinase Lck (LCK)	OT883FG9	LCK_HUMAN	Gene/Protein Processing	[4]

References

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• [2] Down-regulation of survivin in nitric oxide-induced cell growth inhibition and apoptosis of the human lung carcinoma cells. J Biol Chem. 2004 May 7;279(19):20267-76.
• [3] Pharmacological inhibitors of cyclin-dependent kinases. Trends Pharmacol Sci. 2002 Sep;23(9):417-25.
• [4] The specificities of protein kinase inhibitors: an update. Biochem J. 2003 Apr 1;371(Pt 1):199-204. doi: 10.1042/BJ20021535.
• [5] 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta. Bioorg Med Chem Lett. 2004 Jan 19;14(2):413-6.
• [6] Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.
• [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] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [20] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [21] Structure based drug design of crizotinib (PF-02341066), a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK). J Med Chem. 2011 Sep 22;54(18):6342-63. doi: 10.1021/jm2007613. Epub 2011 Aug 18.
• [22] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [23] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [24] Imatinib mesylate inhibits T-cell proliferation in vitro and delayed-type hypersensitivity in vivo. Blood. 2004 Aug 15;104(4):1094-9. doi: 10.1182/blood-2003-12-4266. Epub 2004 Apr 20.
• [25] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [26] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [27] Sorafenib induces cell death in chronic lymphocytic leukemia by translational downregulation of Mcl-1. Leukemia. 2011 May;25(5):838-47. doi: 10.1038/leu.2011.2. Epub 2011 Feb 4.
• [28] Molecular mechanism of action of bisphenol and bisphenol A mediated by oestrogen receptor alpha in growth and apoptosis of breast cancer cells. Br J Pharmacol. 2013 May;169(1):167-78.