Details of the Drug Combination

General Information of Drug Combination (ID: DC7AEVA)

• Drug Combination Name: NVP-LAQ824 + Ruxolitinib
• Indication: Hodgkin lymphoma; Status: Investigative [1]
• Component Drugs:
  NVP-LAQ824 (DM8JWNA): Small molecular drug
  Ruxolitinib (DM7Q98D): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: L-1236
  Zero Interaction Potency (ZIP) Score: 3.347
  Bliss Independence Score: 4.252
  Loewe Additivity Score: 2.087
  LHighest Single Agent (HSA) Score: 4.062

Molecular Interaction Atlas of This Drug Combination

Indication(s) of NVP-LAQ824

Disease Entry	ICD 11	Status	REF
Mood disorder	6A60-6E23	Phase 3	[2]
leukaemia	2A60-2B33	Discontinued in Phase 1/2	[2]
Multiple myeloma	2A83	Investigative	[3]

NVP-LAQ824 Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Histone deacetylase (HDAC)	TTBH0VX	NOUNIPROTAC	Inhibitor	[3]
Histone deacetylase 1 (HDAC1)	TT6R7JZ	HDAC1_HUMAN	Inhibitor	[11]

NVP-LAQ824 Interacts with 10 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[12]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[10]
Retinoic acid receptor beta (RARB)	OT367U3E	RARB_HUMAN	Increases Acetylation	[13]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[10]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[13]
Transgelin (TAGLN)	OTAEZ0KP	TAGL_HUMAN	Increases Expression	[13]
DNA repair protein RAD50 (RAD50)	OTYMU9G1	RAD50_HUMAN	Decreases Expression	[10]
Histone H1.2 (H1-2)	OT0AVI4M	H12_HUMAN	Affects Response To Substance	[10]
p21 protein (HRAS)	OTFYE6AJ	P78460_HUMAN	Increases ADR	[14]
Heat shock protein HSP 90-alpha (HSP90AA1)	OTLG1WPK	HS90A_HUMAN	Increases ADR	[14]

Indication(s) of Ruxolitinib

Disease Entry	ICD 11	Status	REF
Essential thrombocythemia	3B63.1Z	Approved	[4]
High-risk myelofibrosis	2A20.2	Approved	[5]
Myelofibrosis	2A22	Approved	[6]
Myeloproliferative neoplasm	2A20	Approved	[7]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[8]
Pancreatic cancer	2C10	Phase 3	[5]
Atopic dermatitis	EA80	Phase 1/2	[9]
Vitiligo	ED63.0	Phase 1/2	[9]

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	[15]
Janus kinase 1 (JAK-1)	TT6DM01	JAK1_HUMAN	Modulator	[15]
Urokinase plasminogen activator surface receptor (PLAUR)	TTPRL03	UPAR_HUMAN	Inhibitor	[16]
HUMAN janus kinase 1 (JAK-1)	TTWKB01	JAK1_HUMAN	Inhibitor	[17]
HUMAN janus kinase 2 (JAK-2)	TT0F5HE	JAK2_HUMAN	Inhibitor	[17]

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] Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92.
• [3] Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] 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).
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [7] Ruxolitinib FDA Label
• [8] Incyte begins Phase III trial of ruxolitinib to treat Covid-19. 20.April.2020.
• [9] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [10] Role of histone deacetylase inhibitor-induced reactive oxygen species and DNA damage in LAQ-824/fludarabine antileukemic interactions. Mol Cancer Ther. 2008 Oct;7(10):3285-97. doi: 10.1158/1535-7163.MCT-08-0385.
• [11] NVP-LAQ824 is a potent novel histone deacetylase inhibitor with significant activity against multiple myeloma. Blood. 2003 Oct 1;102(7):2615-22.
• [12] The multikinase inhibitor sorafenib potentiates TRAIL lethality in human leukemia cells in association with Mcl-1 and cFLIPL down-regulation. Cancer Res. 2007 Oct 1;67(19):9490-500. doi: 10.1158/0008-5472.CAN-07-0598.
• [13] Antitumor effect of the histone deacetylase inhibitor LAQ824 in combination with 13-cis-retinoic acid in human malignant melanoma. Mol Cancer Ther. 2007 Jan;6(1):70-81. doi: 10.1158/1535-7163.MCT-06-0125.
• [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.
• [15] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [16] Urokinase-type plasminogen activator receptor signaling is critical in nasopharyngeal carcinoma cell growth and metastasis.Cell Cycle. 2014;13(12):1958-69.
• [17] 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.