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

General Information of Drug (ID: DMMAL3I)

• Drug Name: SB-415286 Drug Info
• Synonyms: SB 415286; 264218-23-7; SB-415286; SB415286; 3-(3-chloro-4-hydroxyphenylamino)-4-(2-nitrophenyl)-1H-pyrrole-2,5-dione; 3-(3-chloro-4-hydroxyphenylamino)-4-(4-nitrophenyl)-1H-pyrrole-2,5-dione; CHEMBL322970; 3-(3-chloro-4-hydroxyanilino)-4-(2-nitrophenyl)pyrrole-2,5-dione; 3-[(3-chloro-4-hydroxyphenyl)amino]-4-(2-nitrophenyl)-1H-pyrrole-2,5-dione; 1H-Pyrrol-2,5-dione, 3-((3-chloro-4-hydroxyphenyl)amino)-4-(2-nitrophenyl)-; SMR000568415; SR-01000075855

Indication

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

• Cross-matching ID:
  PubChem CID: 4210951
  ChEBI ID: CHEBI:91107
  CAS Number: CAS 264218-23-7
  TTD Drug ID: DMMAL3I

Molecule-Related Drug Atlas

Drug(s) Targeting Glycogen synthase kinase-3 beta (GSK-3B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AMO-02	DMJRU3A	Myotonic dystrophy	8C71.0	Phase 2/3	[5]
LY2090314	DMTBFE4	Acute myeloid leukaemia	2A60	Phase 2	[6]
Lithium	DMZ3OU6	Bipolar disorder	6A60	Phase 2	[7]
Tideglusib	DME4LA1	Alzheimer disease	8A20	Phase 2	[8]
9-ING-41	DM57TY3	Myelofibrosis	2A20.2	Phase 2	[9]
Neu-120	DMXKOUC	Parkinson disease	8A00.0	Phase 1/2	[10]
KENPAULLONE	DMAGVXW	Discovery agent	N.A.	Patented	[11]
CHIR-99021	DMB8MNU	Allergic inflammation	4A80-4A85	Patented	[12]
TDZD-8	DMG6Q45	Malignant glioma	2A00.0	Patented	[13]
AR-A014418	DMUPN01	Ovarian cancer	2C73	Patented	[2]

Drug(s) Targeting Ribosomal protein S6 kinase beta-1 (S6K1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
M2698	DM3PVBJ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[14]
NNI-362	DMPCV65	Alzheimer disease	8A20	Phase 1	[15]
PF-4708671	DMO0892	Ulcerative colitis	DD71	Clinical trial	[16]
PMID27410995-Compound-Figure3c	DMDQMZT	N. A.	N. A.	Patented	[17]
Pyrimido[4,5-d] pyrimidines and pyrido[4,3-d] pyrimidine derivative 1	DM6O2Q9	N. A.	N. A.	Patented	[17]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[18]
4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol	DMSKJ1X	Discovery agent	N.A.	Investigative	[19]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[20]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[18]
KN-62	DMLZ89P	Discovery agent	N.A.	Investigative	[18]

Drug(s) Affected By Cyclic AMP-responsive element-binding protein 1 (CREB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[21]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[22]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[23]
Selenium	DM25CGV	N. A.	N. A.	Approved	[24]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[25]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[26]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[27]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[27]
Hydroquinone	DM6AVR4	Melasma	ED60.1	Approved	[28]
Ergotidine	DM78IME	Osteoarthritis	FA00-FA05	Approved	[29]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Glycogen synthase kinase-3 beta (GSK-3B)	TTRSMW9	GSK3B_HUMAN	Inhibitor	[2]
Ribosomal protein S6 kinase beta-1 (S6K1)	TTG0U4H	KS6B1_HUMAN	Inhibitor	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cyclic AMP-responsive element-binding protein 1 (CREB1)	OT1MDLA1	CREB1_HUMAN	Post-Translational Modifications	[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: 8019).
• [2] Fragment and knowledge-based design of selective GSK-3beta inhibitors using virtual screening models. Eur J Med Chem. 2009 Jun;44(6):2361-71.
• [3] 3-Anilino-4-arylmaleimides: potent and selective inhibitors of glycogen synthase kinase-3 (GSK-3). Bioorg Med Chem Lett. 2001 Mar 12;11(5):635-9.
• [4] Sirt1 inhibits the transcription factor CREB to regulate pituitary growth hormone synthesis. FASEB J. 2013 Apr;27(4):1561-71. doi: 10.1096/fj.12-220129. Epub 2013 Jan 4.
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Glycogen synthase kinase 3 (GSK-3) inhibitors: a patent update (2014-2015).Expert Opin Ther Pat. 2017 Jun;27(6):657-666.
• [7] The GSK3 kinase inhibitor lithium produces unexpected hyperphosphorylation of -catenin, a GSK3 substrate, in human glioblastoma cells. Biol Open. 2018 Jan 26;7(1):bio030874.
• [8] Evidence for irreversible inhibition of glycogen synthase kinase-3beta by tideglusib. J Biol Chem. 2012 Jan 6;287(2):893-904.
• [9] 9-ING-41, a small molecule inhibitor of GSK-3beta, potentiates the effects of anticancer therapeutics in bladder cancer. Sci Rep. 2019 Dec 27;9(1):19977.
• [10] Company report (Neurim Pharmaceuticals)
• [11] 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta. Bioorg Med Chem Lett. 2004 Jan 19;14(2):413-6.
• [12] Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo. Diabetes. 2003 Mar;52(3):588-95.
• [13] Identification of novel scaffold of benzothiazepinones as non-ATP competitive glycogen synthase kinase-3beta inhibitors through virtual screening. Bioorg Med Chem Lett. 2012 Dec 1;22(23):7232-6.
• [14] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [15] Novel pharmacotherapy: NNI-362, an allosteric p70S6 kinase stimulator, reverses cognitive and neural regenerative deficits in models of aging and disease. Stem Cell Res Ther. 2021 Jan 13;12(1):59.
• [16] Characterization of PF-4708671, a novel and highly specific inhibitor of p70 ribosomal S6 kinase (S6K1). Biochem J. 2010 Oct 15;431(2):245-55.
• [17] Ribosomal S6 kinase (RSK) modulators: a patent review.Expert Opin Ther Pat. 2016 Sep;26(9):1061-78.
• [18] Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.
• [19] 4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. J Med Chem. 2006 Nov 2;49(22):6500-9.
• [20] Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. J Med Chem. 2004 Dec 2;47(25):6239-47.
• [21] Association between treatment-emergent suicidal ideation with citalopram and polymorphisms near cyclic adenosine monophosphate response element binding protein in the STAR*D study. Arch Gen Psychiatry. 2007 Jun;64(6):689-97. doi: 10.1001/archpsyc.64.6.689.
• [22] Cannabidiol upregulates melanogenesis through CB1 dependent pathway by activating p38 MAPK and p42/44 MAPK. Chem Biol Interact. 2017 Aug 1;273:107-114. doi: 10.1016/j.cbi.2017.06.005. Epub 2017 Jun 7.
• [23] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [24] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [25] Distinct genetic profile in peripheral blood mononuclear cells of psoriatic arthritis patients treated with methotrexate and TNF-inhibitors. Clin Rheumatol. 2014 Dec;33(12):1815-21. doi: 10.1007/s10067-014-2807-8. Epub 2014 Oct 24.
• [26] 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.
• [27] Nonclassical action of retinoic acid on the activation of the cAMP response element-binding protein in normal human bronchial epithelial cells. Mol Biol Cell. 2006 Feb;17(2):566-75. doi: 10.1091/mbc.e05-06-0519. Epub 2005 Nov 9.
• [28] p38 MAPK/PP2Ac/TTP pathway on the connection of TNF- and caspases activation on hydroquinone-induced apoptosis. Carcinogenesis. 2013 Apr;34(4):818-27. doi: 10.1093/carcin/bgs409. Epub 2013 Jan 3.
• [29] Glycyrrhizin attenuates histamine-mediated MUC5AC upregulation, inflammatory cytokine production, and aquaporin 5 downregulation through suppressing the NF-B pathway in human nasal epithelial cells. Chem Biol Interact. 2018 Apr 1;285:21-26. doi: 10.1016/j.cbi.2018.02.010. Epub 2018 Feb 13.