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

General Information of Drug (ID: DM5IA9W)

• Drug Name: droxinostat Drug Info
• Synonyms: NS-41080; NS41080

Indication

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

• Cross-matching ID:
  PubChem CID: 568416
  ChEBI ID: CHEBI:94504
  CAS Number: CAS 99873-43-5
  TTD Drug ID: DM5IA9W

Molecule-Related Drug Atlas

Drug(s) Targeting Histone deacetylase 3 (HDAC3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CHR-3996	DMIXPNG	Lymphoma	2A80-2A86	Phase 1/2	[3]
PMID29671355-Compound-62	DMWRS34	N. A.	N. A.	Patented	[4]
PMID29671355-Compound-43	DMVPMWJ	N. A.	N. A.	Patented	[4]
PMID29671355-Compound-25	DMPV0KZ	N. A.	N. A.	Patented	[4]
PMID29671355-Compound-21	DMPJN0M	N. A.	N. A.	Patented	[4]
PMID29671355-Compound-31	DM3H78D	N. A.	N. A.	Patented	[4]
PMID29671355-Compound-56	DM0VBMI	N. A.	N. A.	Patented	[4]
PMID29671355-Compound-67	DM1RPL4	N. A.	N. A.	Patented	[4]
PMID29671355-Compound-44	DM80A3V	N. A.	N. A.	Patented	[4]
PMID29671355-Compound-61	DMXH1G3	N. A.	N. A.	Patented	[4]

Drug(s) Targeting Histone deacetylase 6 (HDAC6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Citarinostat	DMQLODU	Multiple myeloma	2A83	Phase 1	[5]
KA2507	DMW0H9Y	Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]
PMID29671355-Compound-62	DMWRS34	N. A.	N. A.	Patented	[4]
PMID29671355-Compound-43	DMVPMWJ	N. A.	N. A.	Patented	[4]
PMID29671355-Compound-25	DMPV0KZ	N. A.	N. A.	Patented	[4]
PMID29671355-Compound-21	DMPJN0M	N. A.	N. A.	Patented	[4]
PMID29671355-Compound-31	DM3H78D	N. A.	N. A.	Patented	[4]
PMID29671355-Compound-56	DM0VBMI	N. A.	N. A.	Patented	[4]
PMID29671355-Compound-67	DM1RPL4	N. A.	N. A.	Patented	[4]
PMID29671355-Compound-23	DMUBOEX	N. A.	N. A.	Patented	[4]

Drug(s) Targeting Histone deacetylase 8 (HDAC8)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NBM-BMX	DM5OWXA	Solid tumour/cancer	2A00-2F9Z	Phase 1	[6]
PMID29671355-Compound-62	DMWRS34	N. A.	N. A.	Patented	[4]
PMID29671355-Compound-43	DMVPMWJ	N. A.	N. A.	Patented	[4]
PMID29671355-Compound-25	DMPV0KZ	N. A.	N. A.	Patented	[4]
PMID29671355-Compound-21	DMPJN0M	N. A.	N. A.	Patented	[4]
PMID29671355-Compound-31	DM3H78D	N. A.	N. A.	Patented	[4]
PMID29671355-Compound-56	DM0VBMI	N. A.	N. A.	Patented	[4]
PMID29671355-Compound-67	DM1RPL4	N. A.	N. A.	Patented	[4]
PMID29671355-Compound-23	DMUBOEX	N. A.	N. A.	Patented	[4]
PMID29671355-Compound-44	DM80A3V	N. A.	N. A.	Patented	[4]

Drug(s) Affected By CASP8 and FADD-like apoptosis regulator (CFLAR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Beta-carotene	DM0RXBT	Vitamin deficiency	5B55-5B71	Approved	[7]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[8]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[9]
Dactinomycin	DM2YGNW	Adult kidney Wilms tumor		Approved	[10]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[11]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[12]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[13]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[14]
Rifampicin	DM5DSFZ	Non-insulin dependent diabetes	5A11	Approved	[15]
Ethacrynic acid	DM60QMR	Edema	MG29	Approved	[16]

Drug(s) Affected By Poly polymerase 1 (PARP1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[17]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[18]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[19]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[20]
Citalopram	DM2G9AE	Acute coronary syndrome	BA41	Approved	[21]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[22]
Imipramine	DM2NUH3	Depression	6A70-6A7Z	Approved	[21]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[23]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[24]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[25]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Histone deacetylase 3 (HDAC3)	TT4YWTO	HDAC3_HUMAN	Inhibitor	[1]
Histone deacetylase 6 (HDAC6)	TT5ZKDI	HDAC6_HUMAN	Inhibitor	[1]
Histone deacetylase 8 (HDAC8)	TTT6LFV	HDAC8_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
CASP8 and FADD-like apoptosis regulator (CFLAR)	OTX14BAS	CFLAR_HUMAN	Gene/Protein Processing	[2]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Protein Interaction/Cellular Processes	[2]

References

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• [2] 4-(4-Chloro-2-methylphenoxy)-N-hydroxybutanamide (CMH) targets mRNA of the c-FLIP variants and induces apoptosis in MCF-7 human breast cancer cells. Mol Cell Biochem. 2010 Sep;342(1-2):133-142. doi: 10.1007/s11010-010-0477-7. Epub 2010 May 6.
• [3] A phase I pharmacokinetic and pharmacodynamic study of CHR-3996, an oral class I selective histone deacetylase inhibitor in refractory solid tumors. Clin Cancer Res. 2012 May 1;18(9):2687-94.
• [4] HDAC inhibitors: a 2013-2017 patent survey.Expert Opin Ther Pat. 2018 Apr 19:1-17.
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Clinical pipeline report, company report or official report of NatureWise Biotech & Medicals.
• [7] Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human bronchioepithelial cells. Arch Biochem Biophys. 2006 Nov 1;455(1):48-60.
• [8] PGK1 induction by a hydrogen peroxide treatment is suppressed by antioxidants in human colon carcinoma cells. Biosci Biotechnol Biochem. 2008 Jul;72(7):1799-808. doi: 10.1271/bbb.80079. Epub 2008 Jul 7.
• [9] Peripheral blood expression of nuclear factor-kappab-regulated genes is associated with rheumatoid arthritis disease activity and responds differentially to anti-tumor necrosis factor-alpha versus methotrexate. J Rheumatol. 2007 Sep;34(9):1817-22. Epub 2007 Aug 1.
• [10] Combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and actinomycin D induces apoptosis even in TRAIL-resistant human pancreatic cancer cells. Clin Cancer Res. 2001 Feb;7(2):407-14.
• [11] Simvastatin induces apoptosis in human colon cancer cells and in tumor xenografts, and attenuates colitis-associated colon cancer in mice. Int J Cancer. 2008 Aug 15;123(4):951-7. doi: 10.1002/ijc.23593.
• [12] Quercetin potentiates apoptosis by inhibiting nuclear factor-kappaB signaling in H460 lung cancer cells. Biol Pharm Bull. 2013;36(6):944-51. doi: 10.1248/bpb.b12-01004.
• [13] Troglitazone sensitizes tumor cells to TRAIL-induced apoptosis via down-regulation of FLIP and Survivin. Apoptosis. 2006 Sep;11(9):1503-12. doi: 10.1007/s10495-006-8896-3.
• [14] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [15] Rifampicin inhibits CD95-mediated apoptosis of Jurkat T cells via glucocorticoid receptors by modifying the expression of molecules regulating apoptosis. J Clin Immunol. 2002 Jan;22(1):37-47. doi: 10.1023/a:1014256603539.
• [16] Ethacrynic acid and a derivative enhance apoptosis in arsenic trioxide-treated myeloid leukemia and lymphoma cells: the role of glutathione S-transferase p1-1. Clin Cancer Res. 2012 Dec 15;18(24):6690-701. doi: 10.1158/1078-0432.CCR-12-0770. Epub 2012 Oct 18.
• [17] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [18] Evidence of securin-mediated resistance to gefitinib-induced apoptosis in human cancer cells. Chem Biol Interact. 2013 Apr 25;203(2):412-22. doi: 10.1016/j.cbi.2013.03.011. Epub 2013 Mar 22.
• [19] Cigarette smoke and asbestos activate poly-ADP-ribose polymerase in alveolar epithelial cells. J Investig Med. 2001 Jan;49(1):68-76. doi: 10.2310/6650.2001.34092.
• [20] Apoptotic signaling pathways induced by nitric oxide in human lymphoblastoid cells expressing wild-type or mutant p53. Cancer Res. 2004 May 1;64(9):3022-9. doi: 10.1158/0008-5472.can-03-1880.
• [21] The antidepressants imipramine, clomipramine, and citalopram induce apoptosis in human acute myeloid leukemia HL-60 cells via caspase-3 activation. J Biochem Mol Toxicol. 1999;13(6):338-47. doi: 10.1002/(sici)1099-0461(1999)13:6<338::aid-jbt8>3.0.co;2-7.
• [22] Ciprofloxacin mediated cell growth inhibition, S/G2-M cell cycle arrest, and apoptosis in a human transitional cell carcinoma of the bladder cell line. Clin Cancer Res. 2000 Mar;6(3):891-900.
• [23] Investigation of molecular mechanisms underlying the antiproliferative effects of colchicine against PC3 prostate cancer cells. Toxicol In Vitro. 2021 Jun;73:105138. doi: 10.1016/j.tiv.2021.105138. Epub 2021 Mar 6.
• [24] Sulindac enhances adenoviral vector expressing mda-7/IL-24-mediated apoptosis in human lung cancer. Mol Cancer Ther. 2005 Feb;4(2):291-304.
• [25] Methotrexate induces poly(ADP-ribose) polymerase-dependent, caspase 3-independent apoptosis in subsets of proliferating CD4+ T cells. Clin Exp Immunol. 2007 May;148(2):288-95. doi: 10.1111/j.1365-2249.2007.03335.x. Epub 2007 Feb 7.