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

General Information of Drug (ID: DMFPOUC)

• Drug Name: CGP-57380 Drug Info
• Synonyms: CGP 57380; 522629-08-9; CGP-57380; MNK1 Inhibitor; N3-(4-fluorophenyl)-1h-pyrazolo[3,4-d]pyrimidine-3,4-diamine; CGP57380; CHEMBL1240885; C11H9FN6; 4-Amino-5-(4-fluoroanilino)-pyrazolo[3,4-d]pyrimidine; SCHEMBL987991; GTPL6010; CHEMBL576817; SCHEMBL16714452; CHEBI:92749; DTXSID50469941; MolPort-006-725-822; HMS3653G22; HMS3269P13; HMS3263L14; HMS3229K20; HMS3648M14; Tox21_501256; BDBM50130693; 2314AH; NSC741567; MFCD03861062; ZINC13816313; s7421; IN1236; BDBM50298223; AKOS024457265; CCG-206868; NSC-741567; LP01256; NCGC00162380-06

Indication

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

• Cross-matching ID:
  PubChem CID: 11644425
  ChEBI ID: CHEBI:92749
  CAS Number: CAS 522629-08-9
  TTD Drug ID: DMFPOUC

Molecule-Related Drug Atlas

Drug(s) Targeting LCK tyrosine protein kinase (LCK)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dasatinib	DMJV2EK	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[5]
VX-680	DM93YKJ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[5]
JNJ-26483327	DMSQ3AZ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[6]
ISIS-CRP	DMQDUG4	Cardiovascular disease	BA00-BE2Z	Phase 1	[2]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[7]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[7]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[8]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[7]
AMP-PNP	DMTOK1D	Discovery agent	N.A.	Investigative	[9]
BMS-536924	DMXJB4N	Discovery agent	N.A.	Investigative	[10]

Drug(s) Targeting Serine/threonine-protein kinase Sgk1 (SGK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[7]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[7]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[8]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[7]
KN-62	DMLZ89P	Discovery agent	N.A.	Investigative	[7]
GSK-650394	DMNRP2L	Prostate cancer	2C82.0	Investigative	[11]

Drug(s) Targeting Aurora B messenger RNA (AURKB mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PHA-739358	DMGYBZI	Prostate cancer	2C82.0	Phase 2	[12]
Indirubin-3'-monoxime	DMLRQH0	Discovery agent	N.A.	Investigative	[13]
SU 6656	DMF1P6W	Discovery agent	N.A.	Investigative	[2]
6-bromoindirubin-3-oxime	DM12WYV	Discovery agent	N.A.	Investigative	[13]
7-fluoroindirubin-3-oxime	DMQD34N	Discovery agent	N.A.	Investigative	[13]
PMID21742770C1	DME3JMH	Discovery agent	N.A.	Investigative	[14]
Indirubin-3-acetoxime	DM3UR1E	Discovery agent	N.A.	Investigative	[13]
PMID20855207C25	DMNEB6J	Discovery agent	N.A.	Investigative	[15]
Indirubin-3-methoxime	DMZ5ODC	Discovery agent	N.A.	Investigative	[13]
4-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine	DM9MPHF	Discovery agent	N.A.	Investigative	[16]

Drug(s) Affected By Eukaryotic translation initiation factor 4E (EIF4E)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ribavirin	DMEYLH9	Hepatitis C virus infection	1E51.1	Approved	[17]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[18]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[19]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[20]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[21]
Ibuprofen	DM8VCBE	Dysmenorrhea	GA34.3	Approved	[22]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[23]
Momelotinib	DMF98Q0	Myelofibrosis	2A20.2	Approved	[24]
Flurbiprofen	DMGN4BY	Osteoarthritis	FA00-FA05	Approved	[22]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[25]

Drug(s) Affected By MAP kinase-interacting serine/threonine-protein kinase 1 (MKNK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[26]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[27]
Sorbitol	DMAN0DE	Constipation	DD91.1	Approved	[26]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[28]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[29]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[25]
Decitabine	DMQL8XJ	Acute myelogenous leukaemia	2A41	Approved	[30]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[30]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[31]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[32]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Aurora B messenger RNA (AURKB mRNA)	TT9RTBL	AURKB_HUMAN	Inhibitor	[2]
LCK tyrosine protein kinase (LCK)	TT860QF	LCK_HUMAN	Inhibitor	[2]
Serine/threonine-protein kinase Sgk1 (SGK1)	TTTV8EJ	SGK1_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Eukaryotic translation initiation factor 4E (EIF4E)	OTDAWNLA	IF4E_HUMAN	Post-Translational Modifications	[3]
MAP kinase-interacting serine/threonine-protein kinase 1 (MKNK1)	OTGBRJDQ	MKNK1_HUMAN	Gene/Protein Processing	[4]

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: 6010).
• [2] The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.
• [3] Phosphorylation of initiation factor 4E is resistant to SB203580 in cells expressing a drug-resistant mutant of stress-activated protein kinase 2a/p38. Cell Signal. 2003 Aug;15(8):741-9. doi: 10.1016/s0898-6568(03)00008-1.
• [4] Regulation of arsenic trioxide-induced cellular responses by Mnk1 and Mnk2. J Biol Chem. 2008 May 2;283(18):12034-42. doi: 10.1074/jbc.M708816200. Epub 2008 Feb 25.
• [5] 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.
• [6] National Cancer Institute Drug Dictionary (drug id 596693).
• [7] Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.
• [8] Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. J Med Chem. 2004 Dec 2;47(25):6239-47.
• [9] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [10] Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitum... J Med Chem. 2005 Sep 8;48(18):5639-43.
• [11] 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: 8040).
• [12] Potent and selective Aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition. J Med Chem. 2005 Apr 21;48(8):3080-4.
• [13] An integrated computational approach to the phenomenon of potent and selective inhibition of aurora kinases B and C by a series of 7-substituted in... J Med Chem. 2007 Aug 23;50(17):4027-37.
• [14] A Potent and Selective Quinoxalinone-Based STK33 Inhibitor Does Not Show Synthetic Lethality in KRAS-Dependent Cells. ACS Med Chem Lett. 2012 Dec 13;3(12):1034-1038.
• [15] Discovery of orally bioavailable imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors. Bioorg Med Chem Lett. 2010 Nov 15;20(22):6739-43.
• [16] Discovery of a new series of Aurora inhibitors through truncation of GSK1070916. Bioorg Med Chem Lett. 2010 Apr 15;20(8):2552-5.
• [17] Ribavirin inhibits the growth and ascites formation of hepatocellular carcinoma through downregulation of type I CARM1 and type II PRMT5. Toxicol Appl Pharmacol. 2022 Jan 15;435:115829. doi: 10.1016/j.taap.2021.115829. Epub 2021 Dec 14.
• [18] Benzodithiophenes potentiate differentiation of acute promyelocytic leukemia cells by lowering the threshold for ligand-mediated corepressor/coactivator exchange with retinoic acid receptor alpha and enhancing changes in all-trans-retinoic acid-regulated gene expression. Cancer Res. 2005 Sep 1;65(17):7856-65. doi: 10.1158/0008-5472.CAN-05-1056.
• [19] 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.
• [20] Differential Response of Glioma Stem Cells to Arsenic Trioxide Therapy Is Regulated by MNK1 and mRNA Translation. Mol Cancer Res. 2018 Jan;16(1):32-46. doi: 10.1158/1541-7786.MCR-17-0397. Epub 2017 Oct 17.
• [21] A systems biology understanding of the synergistic effects of arsenic sulfide and Imatinib in BCR/ABL-associated leukemia. Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3378-83.
• [22] The p38 MAPK pathway mediates aryl propionic acid induced messenger rna stability of p75 NTR in prostate cancer cells. Cancer Res. 2007 Dec 1;67(23):11402-10. doi: 10.1158/0008-5472.CAN-07-1792.
• [23] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [24] The effect of quercetin nanoparticle on cervical cancer progression by inducing apoptosis, autophagy and anti-proliferation via JAK2 suppression. Biomed Pharmacother. 2016 Aug;82:595-605. doi: 10.1016/j.biopha.2016.05.029. Epub 2016 Jun 9.
• [25] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [26] The phosphorylation of eukaryotic initiation factor eIF4E in response to phorbol esters, cell stresses, and cytokines is mediated by distinct MAP kinase pathways. J Biol Chem. 1998 Apr 17;273(16):9373-7. doi: 10.1074/jbc.273.16.9373.
• [27] Aberrantly expressed genes in HaCaT keratinocytes chronically exposed to arsenic trioxide. Biomark Insights. 2011 Feb 8;6:7-16.
• [28] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [29] 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.
• [30] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [31] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [32] Estrogen Regulates MAPK-Related Genes through Genomic and Nongenomic Interactions between IGF-I Receptor Tyrosine Kinase and Estrogen Receptor-Alpha Signaling Pathways in Human Uterine Leiomyoma Cells. J Signal Transduct. 2012;2012:204236. doi: 10.1155/2012/204236. Epub 2012 Oct 9.