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

General Information of Drug (ID: DMCKPG4)

• Drug Name: ABC294640 Drug Info
• Synonyms: ABC294640; 915385-81-8; Opaganib; ABC-294640; CHEMBL2158685; ABC 294640; UNII-DRG21OQ517; DRG21OQ517; Yeliva; SCHEMBL1548333; GTPL6624; CHEBI:124965; MolPort-044-560-286; HMS3402P05; BCP08959; EX-A1962; BDBM50393642; 3-(4-chlorophenyl)-N-(pyridin-4-ylmethyl)adamantane-1-carboxamide; AKOS027327311; CS-0877; SB17167; DB12764; API0017247; HY-16015; S7174; BRD-A70814879-003-01-8; ABC294640; 915385-81-8; ABC-294640

Indication

Disease Entry	ICD 11	Status	REF
Advanced solid tumour	2A00-2F9Z	Phase 3	[1]
Cholangiocarcinoma	2C12.10	Phase 2	[2]
Hepatocellular carcinoma	2C12.02	Phase 2	[2]
Multiple myeloma	2A83	Phase 1/2	[2]

• Cross-matching ID:
  PubChem CID: 15604015
  ChEBI ID: CHEBI:124965
  CAS Number: CAS 915385-81-8
  TTD Drug ID: DMCKPG4

Molecule-Related Drug Atlas

Drug(s) Targeting Sphingosine kinase 2 (SPHK2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(R)-2-amino-4-hydroxy-N-(4-octylphenyl)butanamide	DMA1EFL	Discovery agent	N.A.	Investigative	[5]
(S)-2-amino-6-hydroxy-N-(4-octylphenyl)hexanamide	DMG0CSZ	Discovery agent	N.A.	Investigative	[5]
(R)-2-amino-3-(4-octylphenylamino)propan-1-ol	DMZXT34	Discovery agent	N.A.	Investigative	[5]
ROMe	DMAROW1	Discovery agent	N.A.	Investigative	[6]
DIMETHYLSPINGOSINE	DM1OKN0	N. A.	N. A.	Investigative	[7]
(S)-2-amino-4-hydroxy-N-(4-octylphenyl)butanamide	DM8A1HG	Discovery agent	N.A.	Investigative	[5]

Drug(s) Affected By Estrogen receptor (ESR1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[8]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[9]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[10]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[11]
Lapatinib	DM3BH1Y	Breast cancer	2C60-2C65	Approved	[12]
Liraglutide	DM3FXPS	Non-insulin dependent diabetes	5A11	Approved	[13]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[14]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[15]
Procaine	DM4LSNE	Anaesthesia	9A78.6	Approved	[11]
Estrone	DM5T6US	Acne vulgaris	ED80	Approved	[16]

Drug(s) Affected By RAC-alpha serine/threonine-protein kinase (AKT1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Capivasertib	DM9SKW8	Breast cancer	2C60-2C65	Approved	[17]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[18]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[19]
Beta-carotene	DM0RXBT	Vitamin deficiency	5B55-5B71	Approved	[20]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[21]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[22]
Imiquimod	DM1TMA3	Alopecia areata	ED70.2	Approved	[23]
Selenium	DM25CGV	N. A.	N. A.	Approved	[24]
Methimazole	DM25FL8	Hyperthyroidism	5A02	Approved	[25]
Ribavirin	DMEYLH9	Hepatitis C virus infection	1E51.1	Approved	[26]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Sphingosine kinase 2 (SPHK2)	TTCN0M9	SPHK2_HUMAN	Modulator	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Gene/Protein Processing	[4]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_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: 6624).
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond. Nat Rev Drug Discov. 2013 Sep;12(9):688-702.
• [4] Antiestrogenic effects of the novel sphingosine kinase-2 inhibitor ABC294640. Endocrinology. 2010 Nov;151(11):5124-35. doi: 10.1210/en.2010-0420. Epub 2010 Sep 22.
• [5] Discovery of novel sphingosine kinase 1 inhibitors. Bioorg Med Chem Lett. 2009 Nov 1;19(21):6119-21.
• [6] (R)-FTY720 methyl ether is a specific sphingosine kinase 2 inhibitor: Effect on sphingosine kinase 2 expression in HEK 293 cells and actin rearrangement and survival of MCF-7 breast cancer cells. Cell Signal. 2011 Oct;23(10):1590-5.
• [7] Synthesis and evaluation of sphingosine analogues as inhibitors of sphingosine kinases. J Med Chem. 2009 Jun 25;52(12):3618-26.
• [8] Estrogen-like activity of metals in MCF-7 breast cancer cells. Endocrinology. 2003 Jun;144(6):2425-36. doi: 10.1210/en.2002-221054.
• [9] Cross-talk between non-genomic and genomic signalling pathways--distinct effect profiles of environmental estrogens. Toxicol Appl Pharmacol. 2010 Jun 1;245(2):160-70. doi: 10.1016/j.taap.2010.02.015. Epub 2010 Mar 4.
• [10] Bidirectional cross talk between ERalpha and EGFR signalling pathways regulates tamoxifen-resistant growth. Breast Cancer Res Treat. 2006 Mar;96(2):131-46. doi: 10.1007/s10549-005-9070-2. Epub 2005 Oct 27.
• [11] Sensitivity of human dental pulp cells to eighteen chemical agents used for endodontic treatments in dentistry. Odontology. 2013 Jan;101(1):43-51.
• [12] The dual ErbB1/ErbB2 inhibitor, lapatinib (GW572016), cooperates with tamoxifen to inhibit both cell proliferation- and estrogen-dependent gene expression in antiestrogen-resistant breast cancer. Cancer Res. 2005 Jan 1;65(1):18-25.
• [13] Antitumoral activity of liraglutide, a new DNMT inhibitor in breast cancer cells in vitro and in vivo. Chem Biol Interact. 2021 Nov 1;349:109641. doi: 10.1016/j.cbi.2021.109641. Epub 2021 Sep 14.
• [14] Estrogen receptor alpha mediates the proliferative but not the cytotoxic dose-dependent effects of two major phytoestrogens on human breast cancer cells. Mol Pharmacol. 2001 Sep;60(3):595-602.
• [15] Novel retinoic acid metabolism blocking agents have potent inhibitory activities on human breast cancer cells and tumour growth. Br J Cancer. 2007 Apr 23;96(8):1204-15. doi: 10.1038/sj.bjc.6603705. Epub 2007 Mar 27.
• [16] Prediction of the combined effects of multiple estrogenic chemicals on MCF-7 human breast cancer cells and a preliminary molecular exploration of the estrogenic proliferative effects and related gene expression. Ecotoxicol Environ Saf. 2018 Sep 30;160:1-9. doi: 10.1016/j.ecoenv.2018.05.025. Epub 2018 May 21.
• [17] Inhibition of cholesterol metabolism underlies synergy between mTOR pathway inhibition and chloroquine in bladder cancer cells. Oncogene. 2016 Aug 25;35(34):4518-28. doi: 10.1038/onc.2015.511. Epub 2016 Feb 8.
• [18] Nicotine-induced survival signaling in lung cancer cells is dependent on their p53 status while its down-regulation by curcumin is independent. Mol Cancer. 2010 Aug 20;9:220.
• [19] Role of miRNA in the regulation of cannabidiol-mediated apoptosis in neuroblastoma cells. Oncotarget. 2019 Jan 1;10(1):45-59. doi: 10.18632/oncotarget.26534. eCollection 2019 Jan 1.
• [20] -Carotene Induces Apoptosis in Human Esophageal Squamous Cell Carcinoma Cell Lines via the Cav-1/AKT/NF-B Signaling Pathway. J Biochem Mol Toxicol. 2016 Mar;30(3):148-57. doi: 10.1002/jbt.21773. Epub 2016 Jan 6.
• [21] Dihydromyricetin suppresses tumor growth via downregulation of the EGFR/Akt/survivin signaling pathway. J Biochem Mol Toxicol. 2023 Jun;37(6):e23328. doi: 10.1002/jbt.23328. Epub 2023 Feb 19.
• [22] Oxidative stress induces parallel autophagy and mitochondria dysfunction in human glioma U251 cells. Toxicol Sci. 2009 Aug;110(2):376-88. doi: 10.1093/toxsci/kfp101. Epub 2009 May 18.
• [23] Effect of toll-like receptor 7 and 9 targeted therapy to prevent the development of hepatocellular carcinoma. Liver Int. 2015 Mar;35(3):1063-76. doi: 10.1111/liv.12626. Epub 2014 Jul 30.
• [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] Low-expressional IGF1 mediated methimazole-induced liver developmental toxicity in fetal mice. Toxicology. 2018 Sep 1;408:70-79. doi: 10.1016/j.tox.2018.07.004. Epub 2018 Jul 7.
• [26] Ribavirin augments doxorubicin's efficacy in human hepatocellular carcinoma through inhibiting doxorubicin-induced eIF4E activation. J Biochem Mol Toxicol. 2018 Jan;32(1). doi: 10.1002/jbt.22007. Epub 2017 Nov 7.