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

General Information of Drug (ID: DMWSLTB)

• Drug Name: 5,11-Dimethyl-6H-pyrido[4,3-b]carbazol-9-ol Drug Info
• Synonyms: 9-Hydroxyellipticine; 9-Hydroxyellipticin; 51131-85-2; 5,11-dimethyl-6H-pyrido[4,3-b]carbazol-9-ol; Hydroxyellipticine; ELLIPTICINE, 9-HYDROXY-; UNII-9G4A3ET6XG; IGIG 929; Hydroxy-9 ellipticine [French]; EINECS 257-000-0; NSC 237070; NSC 210717; 9G4A3ET6XG; CHEMBL26559; CHEBI:88297; C17H14N2O; 5,11-Dimethyl-6H-pyrido(4,3-b)carbazol-9-ol; 6H-Pyrido(4,3-b)carbazol-9-ol, 5,11-dimethyl-; 6H-Pyrido[4,3-b]carbazol-9-ol, 5,11-dimethyl-; 9-hydroxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazole; Hydroxy-9 ellipticine

Indication

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

• Cross-matching ID:
  PubChem CID: 91643
  ChEBI ID: CHEBI:88297
  CAS Number: CAS 51131-85-2
  TTD Drug ID: DMWSLTB

Molecule-Related Drug Atlas

Drug(s) Targeting Platelet-derived growth factor receptor alpha (PDGFRA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[3]
Ripretinib	DM958QB	Gastrointestinal stromal tumour	2B5B	Approved	[4]
Olaratumab	DMNYOIX	Soft tissue sarcoma	2B57	Approved	[5]
Avapritinib	DMK2GZX	Gastrointestinal stromal tumour	2B5B	Approved	[6]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[7]
CP-868596	DMZIM37	Gastrointestinal cancer	2C11	Phase 3	[8]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[9]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[10]
MP470	DMELUAK	Solid tumour/cancer	2A00-2F9Z	Phase 2	[11]
MEDI-575	DMI9WVM	Glioblastoma multiforme	2A00.0	Phase 2	[12]

Drug(s) Targeting Tyrosine-protein kinase Kit (KIT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[13]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[14]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[15]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[16]
Ponatinib	DMYGJQO	Acute lymphoblastic leukaemia	2A85	Approved	[16]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[17]
Pexidartinib	DMS2J0Z	Tenosynovial giant cell tumour	2F7B	Approved	[18]
Ripretinib	DM958QB	Gastrointestinal stromal tumour	2B5B	Approved	[4]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[9]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[10]

Drug(s) Targeting Fibroblast growth factor receptor 3 (FGFR3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pemigatinib	DM819JF	Cholangiocarcinoma	2C12.10	Approved	[19]
Trapidil	DMY67U8	Acute coronary syndrome	BA41	Phase 4	[20]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[7]
TKI258	DMYLT67	Renal cell carcinoma	2C90	Phase 3	[13]
BMS-582664	DMDAN8H	Hepatocellular carcinoma	2C12.02	Phase 3	[13]
Debio 1347	DMZW50O	Solid tumour/cancer	2A00-2F9Z	Phase 2	[21]
B-701	DMOMDA4	Bladder cancer	2C94	Phase 2	[22]
Recifercept	DML8N3Y	Achondroplasia	LD24.00	Phase 2	[23]
MK-2461	DM21WBH	Alzheimer disease	8A20	Phase 1/2	[24]
AEE-788	DMEOS5K	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[13]

Drug(s) Affected By DNA topoisomerase 2-alpha (TOP2A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[25]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[26]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[27]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[28]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[29]
Lapatinib	DM3BH1Y	Breast cancer	2C60-2C65	Approved	[30]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[31]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[32]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[33]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[34]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Fibroblast growth factor receptor 3 (FGFR3)	TTST7KB	FGFR3_HUMAN	Inhibitor	[1]
Platelet-derived growth factor receptor alpha (PDGFRA)	TT8FYO9	PGFRA_HUMAN	Inhibitor	[1]
Tyrosine-protein kinase Kit (KIT)	TTX41N9	KIT_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
DNA topoisomerase 2-alpha (TOP2A)	OT6LPS08	TOP2A_HUMAN	Drug Response	[2]

References

• [1] Molecular modeling of wild-type and D816V c-Kit inhibition based on ATP-competitive binding of ellipticine derivatives to tyrosine kinases. J Med Chem. 2005 Oct 6;48(20):6194-201.
• [2] Old drug, new target: ellipticines selectively inhibit RNA polymerase I transcription. J Biol Chem. 2013 Feb 15;288(7):4567-82. doi: 10.1074/jbc.M112.411611. Epub 2013 Jan 4.
• [3] Discovery of 5-[5-fluoro-2-oxo-1,2- dihydroindol-(3Z)-ylidenemethyl]-2,4- dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, a novel... J Med Chem. 2003 Mar 27;46(7):1116-9.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [5] A phase I study of olaratumab, an anti-platelet-derived growth factor receptor alpha (PDGFRalpha) monoclonal antibody, in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2014 Mar;73(3):595-604.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [7] E-3810 is a potent dual inhibitor of VEGFR and FGFR that exerts antitumor activity in multiple preclinical models. Cancer Res. 2011 Feb 15;71(4):1396-405.
• [8] The FLT3 and PDGFR inhibitor crenolanib is a substrate of the multidrug resistance protein ABCB1 but does not inhibit transport function at pharmacologically relevant concentrations.Invest New Drugs.2015 Apr;33(2):300-9.
• [9] Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
• [10] National Cancer Institute Drug Dictionary (drug id 452042).
• [11] Phase 1B study of amuvatinib in combination with five standard cancer therapies in adults with advanced solid tumors. Cancer Chemother Pharmacol. 2014 Jul;74(1):195-204.
• [12] Clinical pipeline report, company report or official report of MedImmune (2011).
• [13] 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.
• [14] Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling.Mol Cancer Ther.2008 Oct;7(10):3129-40.
• [15] New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven a... J Med Chem. 2000 Jun 15;43(12):2310-23.
• [16] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [17] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [18] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [19] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [20] Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
• [21] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [22] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [23] In vitro and in vivo characterization of Recifercept, a soluble fibroblast growth factor receptor 3, as treatment for achondroplasia. PLoS One. 2020 Dec 28;15(12):e0244368.
• [24] MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.
• [25] Incidence of mutation and deletion in topoisomerase II alpha mRNA of etoposide and mAMSA-resistant cell lines. Jpn J Cancer Res. 2001 Oct;92(10):1133-7. doi: 10.1111/j.1349-7006.2001.tb01069.x.
• [26] HU-331 and Oxidized Cannabidiol Act as Inhibitors of Human Topoisomerase II and . Chem Res Toxicol. 2018 Feb 19;31(2):137-144. doi: 10.1021/acs.chemrestox.7b00302. Epub 2018 Jan 8.
• [27] Gene expression profiles with activation of the estrogen receptor alpha-selective estrogen receptor modulator complex in breast cancer cells expressing wild-type estrogen receptor. Cancer Res. 2002 Aug 1;62(15):4419-26.
• [28] Interactions between the etoposide derivative F14512 and human type II topoisomerases: implications for the C4 spermine moiety in promoting enzyme-mediated DNA cleavage. Biochemistry. 2011 Apr 19;50(15):3240-9. doi: 10.1021/bi200094z. Epub 2011 Mar 28.
• [29] Methotrexate modulates folate phenotype and inflammatory profile in EA.hy 926 cells. Eur J Pharmacol. 2014 Jun 5;732:60-7.
• [30] The involvement of hepatic cytochrome P450s in the cytotoxicity of lapatinib. Toxicol Sci. 2023 Dec 21;197(1):69-78. doi: 10.1093/toxsci/kfad099.
• [31] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [32] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [33] 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.
• [34] Arsenic trioxide exposure to ovarian carcinoma cells leads to decreased level of topoisomerase II and cytotoxicity. Int J Gynecol Cancer. 2006 Jul-Aug;16(4):1552-6. doi: 10.1111/j.1525-1438.2006.00626.x.