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

General Information of Drug (ID: DMYJV4I)

• Drug Name: SL-327 Drug Info
• Synonyms: SL327

Indication

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

• Cross-matching ID:
  PubChem CID: 9549284
  ChEBI ID: CHEBI:92211
  CAS Number: CAS 305350-87-2
  TTD Drug ID: DMYJV4I

Molecule-Related Drug Atlas

Drug(s) Targeting MAPK/ERK kinase kinase (MAP3K)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ARRY-162	DM1P6FR	Melanoma	2C30	Approved	[4]
Trametinib	DM2JGQ3	Melanoma	2C30	Approved	[5]
BAY 86-9766	DMPW5SB	Solid tumour/cancer	2A00-2F9Z	Phase 3	[6]
Selumetinib	DMC7W6R	Neurofibromatosis type 1	LD2D.10	Phase 3	[7]
MSC1936369B	DMH1DYU	Colorectal cancer	2B91.Z	Phase 2	[8]
RO-5126766	DM3U9BY	Non-small-cell lung cancer	2C25	Phase 2	[9]
E6201	DMOSL9P	Psoriasis vulgaris	EA90	Phase 2	[10]
PD-0325901	DM27D4J	Breast cancer	2C60-2C65	Phase 2	[4]
WX-554	DMRABOS	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[4]
RG7304	DMGFAVQ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[11]

Drug(s) Affected By Aryl hydrocarbon receptor (AHR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[12]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[13]
Citalopram	DM2G9AE	Acute coronary syndrome	BA41	Approved	[14]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[15]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[16]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[17]
Omeprazole	DM471KJ	Cystic fibrosis	CA25	Approved	[18]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[19]
Rifampicin	DM5DSFZ	Non-insulin dependent diabetes	5A11	Approved	[20]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[21]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
MAPK/ERK kinase kinase (MAP3K)	TTROQ37	NOUNIPROTAC	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Aryl hydrocarbon receptor (AHR)	OTFE4EYE	AHR_HUMAN	Gene/Protein Processing	[3]

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: 6008).
• [2] A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8.
• [3] ERK kinase inhibition stabilizes the aryl hydrocarbon receptor: implications for transcriptional activation and protein degradation. J Biol Chem. 2005 Feb 11;280(6):4350-9.
• [4] MEK and the inhibitors: from bench to bedside. J Hematol Oncol. 2013; 6: 27.
• [5] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [6] RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancer.Cancer Res.2009 Sep 1;69(17):6839-47.
• [7] Intrinsic resistance to selumetinib, a selective inhibitor of MEK1/2, by cAMP-dependent protein kinase A activation in human lung and colorectal cancer cells.Br J Cancer.2012 May 8;106(10):1648-59.
• [8] Antitumor activity of pimasertib, a selective MEK 1/2 inhibitor, in combination with PI3K/mTOR inhibitors or with multi-targeted kinase inhibitors in pimasertib-resistant human lung and colorectal cancer cells. Int J Cancer. 2013 Nov;133(9):2089-101.
• [9] The dual RAF/MEK inhibitor CH5126766/RO5126766 may be a potential therapy for RAS-mutated tumor cells.PLoS One.2014 Nov 25;9(11):e113217.
• [10] E6201, a novel kinase inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-1 and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase-1: in vivo effects on cutaneous inflammatory responses by topical administration. J Pharmacol Exp Ther. 2010 Oct;335(1):23-31.
• [11] Clinical pipeline report, company report or official report of Roche.
• [12] Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
• [13] Oxidative stress modulates expression of immune checkpoint genes via activation of AhR signaling. Toxicol Appl Pharmacol. 2022 Dec 15;457:116314. doi: 10.1016/j.taap.2022.116314. Epub 2022 Nov 9.
• [14] Profiling of enantiopure drugs towards aryl hydrocarbon (AhR), glucocorticoid (GR) and pregnane X (PXR) receptors in human reporter cell lines. Chem Biol Interact. 2014 Feb 5;208:64-76. doi: 10.1016/j.cbi.2013.11.018. Epub 2013 Dec 6.
• [15] Involvement of cytoskeleton in AhR-dependent CYP1A1 expression. Curr Drug Metab. 2006 Apr;7(3):301-13. doi: 10.2174/138920006776359310.
• [16] Sulindac and its metabolites induce carcinogen metabolizing enzymes in human colon cancer cells. Int J Cancer. 2008 Mar 1;122(5):990-8.
• [17] Quercetin, quercetin glycosides and taxifolin differ in their ability to induce AhR activation and CYP1A1 expression in HepG2 cells. Phytother Res. 2012 Nov;26(11):1746-52.
• [18] Omeprazole inhibits pancreatic cancer cell invasion through a nongenomic aryl hydrocarbon receptor pathway. Chem Res Toxicol. 2015 May 18;28(5):907-18.
• [19] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [20] Expression and inducibility of cytochrome P450s (CYP1A1, 2B6, 2E1, 3A4) in human cord blood CD34(+) stem cell-derived differentiating neuronal cells. Toxicol Sci. 2012 Oct;129(2):392-410.
• [21] Induction of paraoxonase 1 and apolipoprotein A-I gene expression by aspirin. J Lipid Res. 2008 Oct;49(10):2142-8.