Details of the Drug Combination

General Information of Drug Combination (ID: DCZFDS2)

• Drug Combination Name: Tacedinaline + Ruxolitinib
• Indication: Hodgkin lymphoma; Status: Investigative [1]
• Component Drugs:
  Tacedinaline (DM1Z74X): Small molecular drug
  Ruxolitinib (DM7Q98D): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: L-1236
  Zero Interaction Potency (ZIP) Score: 31.52
  Bliss Independence Score: 30.75
  Loewe Additivity Score: 6.43
  LHighest Single Agent (HSA) Score: 15.7

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Tacedinaline

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[2]

Tacedinaline Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Histone deacetylase 1 (HDAC1)	TT6R7JZ	HDAC1_HUMAN	Inhibitor	[10]

Tacedinaline Interacts with 16 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Putative POTE ankyrin domain family member M (POTEM)	OT7L2HGH	POTEM_HUMAN	Increases Expression	[9]
Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1)	OTTO6ZP4	AT1B1_HUMAN	Increases Expression	[9]
Interferon alpha-inducible protein 6 (IFI6)	OTWOOAM4	IFI6_HUMAN	Increases Expression	[9]
Glycine dehydrogenase (GLDC)	OTVVDNW0	GCSP_HUMAN	Increases Expression	[9]
Interleukin-3 receptor subunit alpha (IL3RA)	OTDC3Y8O	IL3RA_HUMAN	Increases Expression	[9]
G-protein coupled receptor 183 (GPR183)	OTRILX7G	GP183_HUMAN	Decreases Expression	[9]
Isopentenyl-diphosphate Delta-isomerase 1 (IDI1)	OTGM06VJ	IDI1_HUMAN	Increases Expression	[9]
Enhancer of filamentation 1 (NEDD9)	OTGCFN4M	CASL_HUMAN	Increases Expression	[9]
Transcriptional protein SWT1 (SWT1)	OTY4AFM1	SWT1_HUMAN	Increases Expression	[9]
Centrosomal protein of 68 kDa (CEP68)	OTZDM4J1	CEP68_HUMAN	Increases Expression	[9]
Sialidase-1 (NEU1)	OTH9BY8Y	NEUR1_HUMAN	Decreases Expression	[9]
PH and SEC7 domain-containing protein 3 (PSD3)	OTTN9B9O	PSD3_HUMAN	Increases Expression	[9]
Ral guanine nucleotide dissociation stimulator-like 1 (RGL1)	OTY6ZHVA	RGL1_HUMAN	Increases Expression	[9]
ERBB receptor feedback inhibitor 1 (ERRFI1)	OT7VZ2IZ	ERRFI_HUMAN	Increases Expression	[9]
Transmembrane and coiled-coil domain protein 3 (TMCC3)	OTAIQ6V6	TMCC3_HUMAN	Increases Expression	[9]
Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1)	OTJQL0I3	HEY1_HUMAN	Increases Expression	[9]

Indication(s) of Ruxolitinib

Disease Entry	ICD 11	Status	REF
Essential thrombocythemia	3B63.1Z	Approved	[3]
High-risk myelofibrosis	2A20.2	Approved	[4]
Myelofibrosis	2A22	Approved	[5]
Myeloproliferative neoplasm	2A20	Approved	[6]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[7]
Pancreatic cancer	2C10	Phase 3	[4]
Atopic dermatitis	EA80	Phase 1/2	[8]
Vitiligo	ED63.0	Phase 1/2	[8]

Ruxolitinib Interacts with 5 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Janus kinase 2 (JAK-2)	TTRMX3V	JAK2_HUMAN	Modulator	[11]
Janus kinase 1 (JAK-1)	TT6DM01	JAK1_HUMAN	Modulator	[11]
Urokinase plasminogen activator surface receptor (PLAUR)	TTPRL03	UPAR_HUMAN	Inhibitor	[12]
HUMAN janus kinase 1 (JAK-1)	TTWKB01	JAK1_HUMAN	Inhibitor	[13]
HUMAN janus kinase 2 (JAK-2)	TT0F5HE	JAK2_HUMAN	Inhibitor	[13]

Ruxolitinib Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Mitogen-activated protein kinase 14 (MAPK14)	OT5TCO3O	MK14_HUMAN	Increases ADR	[14]

References

• [1] Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.
• [2] 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: 8367).
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] 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: 5688).
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [6] Ruxolitinib FDA Label
• [7] Incyte begins Phase III trial of ruxolitinib to treat Covid-19. 20.April.2020.
• [8] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [9] Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells. Arch Toxicol. 2021 May;95(5):1631-1645. doi: 10.1007/s00204-021-03014-2. Epub 2021 Mar 26.
• [10] Histone deacetylase inhibitors in cancer therapy: latest developments, trends and medicinal chemistry perspective. Anticancer Agents Med Chem. 2007 Sep;7(5):576-92.
• [11] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [12] Urokinase-type plasminogen activator receptor signaling is critical in nasopharyngeal carcinoma cell growth and metastasis.Cell Cycle. 2014;13(12):1958-69.
• [13] The Use of Anti-Inflammatory Drugs in the Treatment of People With Severe Coronavirus Disease 2019 (COVID-19): The Perspectives of Clinical Immunologists From China. Clin Immunol. 2020 May;214:108393.
• [14] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.