Details of the Drug Combination

General Information of Drug Combination (ID: DC2HNQ5)

• Drug Combination Name: dioscin + Ruxolitinib
• Indication: Hodgkin lymphoma; Status: Investigative [1]
• Component Drugs:
  dioscin (DM5H2W9): Small molecular drug
  Ruxolitinib (DM7Q98D): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: L-1236
  Zero Interaction Potency (ZIP) Score: 13.546
  Bliss Independence Score: 10.933
  Loewe Additivity Score: 1.986
  LHighest Single Agent (HSA) Score: 4.609

Molecular Interaction Atlas of This Drug Combination

Indication(s) of dioscin

Disease Entry	ICD 11	Status	REF
Hepatic fibrosis	DB93.0	Preclinical	[2]

dioscin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
C-X-C chemokine receptor type 3 (CXCR3)	TT1UCIJ	CXCR3_HUMAN	Antagonist	[10]

dioscin Interacts with 54 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	[9]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Increases Expression	[9]
Serine/threonine-protein kinase Chk2 (CHEK2)	OT8ZPCNS	CHK2_HUMAN	Decreases Expression	[9]
Cyclin-dependent kinase 1 (CDK1)	OTW1SC2N	CDK1_HUMAN	Decreases Expression	[9]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[9]
Cytochrome P450 2C9 (CYP2C9)	OTGLBN29	CP2C9_HUMAN	Increases Expression	[9]
G2/mitotic-specific cyclin-B1 (CCNB1)	OT19S7E5	CCNB1_HUMAN	Decreases Expression	[9]
Ribosomal protein S6 kinase beta-1 (RPS6KB1)	OTAELNGX	KS6B1_HUMAN	Decreases Expression	[9]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Expression	[9]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[9]
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB)	OTO8JQJA	PK3CB_HUMAN	Decreases Expression	[9]
Serine/threonine-protein kinase mTOR (MTOR)	OTHH8KU7	MTOR_HUMAN	Decreases Expression	[9]
Mitogen-activated protein kinase 8 (MAPK8)	OTEREYS5	MK08_HUMAN	Increases Expression	[9]
Mitogen-activated protein kinase 9 (MAPK9)	OTCEVJ9E	MK09_HUMAN	Increases Expression	[9]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Expression	[9]
Tumor necrosis factor receptor type 1-associated DEATH domain protein (TRADD)	OTBOSJHO	TRADD_HUMAN	Increases Expression	[9]
Caspase-10 (CASP10)	OTE6J88E	CASPA_HUMAN	Increases Expression	[9]
Tumor necrosis factor receptor superfamily member 25 (TNFRSF25)	OTVZ7I3A	TNR25_HUMAN	Increases Expression	[9]
Bcl-2-binding component 3, isoforms 3/4 (BBC3)	OTUAXDAY	BBC3B_HUMAN	Increases Expression	[9]
Diablo IAP-binding mitochondrial protein (DIABLO)	OTHJ9MCZ	DBLOH_HUMAN	Increases Expression	[9]
5'-AMP-activated protein kinase subunit beta-1 (PRKAB1)	OT1OG4QZ	AAKB1_HUMAN	Increases Expression	[9]
Apoptotic protease-activating factor 1 (APAF1)	OTJWIVY0	APAF_HUMAN	Decreases Expression	[11]
Serine/threonine-protein kinase Chk1 (CHEK1)	OTTTI622	CHK1_HUMAN	Decreases Expression	[11]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Expression	[12]
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Increases Expression	[13]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[12]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Expression	[14]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Decreases Expression	[11]
Cyclin-dependent kinase 4 (CDK4)	OT7EP05T	CDK4_HUMAN	Decreases Expression	[11]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A)	OT2D9DOV	TNR1A_HUMAN	Increases Expression	[12]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Decreases Expression	[11]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[11]
G1/S-specific cyclin-E1 (CCNE1)	OTLD7UID	CCNE1_HUMAN	Decreases Expression	[11]
Cyclin-dependent kinase 2 (CDK2)	OTB5DYYZ	CDK2_HUMAN	Decreases Expression	[11]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[12]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Decreases Degradation	[14]
Catenin beta-1 (CTNNB1)	OTZ932A3	CTNB1_HUMAN	Increases Expression	[13]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Decreases Expression	[11]
Cyclin-dependent kinase inhibitor 2A (CDKN2A)	OTN0ZWAE	CDN2A_HUMAN	Increases Expression	[11]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Increases Expression	[11]
Tumor necrosis factor ligand superfamily member 6 (FASLG)	OTZARCHH	TNFL6_HUMAN	Increases Expression	[12]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Decreases Expression	[11]
BH3-interacting domain death agonist (BID)	OTOSHSHU	BID_HUMAN	Decreases Expression	[12]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Increases Expression	[11]
Cyclin-dependent kinase 6 (CDK6)	OTR95N0X	CDK6_HUMAN	Decreases Expression	[11]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[11]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[12]
Forkhead box protein O1 (FOXO1)	OTPJRB6D	FOXO1_HUMAN	Increases Expression	[11]
TNF receptor-associated factor 1 (TRAF1)	OTTLM5RU	TRAF1_HUMAN	Increases Expression	[12]
FAS-associated death domain protein (FADD)	OTV7GFHH	FADD_HUMAN	Increases Expression	[12]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Decreases Expression	[11]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Increases Expression	[12]
Estrogen receptor beta (ESR2)	OTXNR2WQ	ESR2_HUMAN	Increases Expression	[13]
Bcl2-associated agonist of cell death (BAD)	OT63ERYM	BAD_HUMAN	Increases Expression	[11]

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	[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	[18]

References

• [1] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [2] Drugs and Targets in Fibrosis. Front Pharmacol. 2017 Nov 23;8:855.
• [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] Molecular mechanism and inhibitory targets of dioscin in HepG2 cells. Food Chem Toxicol. 2018 Oct;120:143-154.
• [10] Discovery of structurally diverse natural product antagonists of chemokine receptor CXCR3. Mol Divers. 2005;9(1-3):123-9.
• [11] Dioscin inhibits human endometrial carcinoma proliferation via G0/G1 cell cycle arrest and mitochondrial-dependent signaling pathway. Food Chem Toxicol. 2021 Feb;148:111941. doi: 10.1016/j.fct.2020.111941. Epub 2020 Dec 24.
• [12] Cytotoxicity of dioscin in human gastric carcinoma cells through death receptor and mitochondrial pathways. J Appl Toxicol. 2013 Aug;33(8):712-22. doi: 10.1002/jat.2715. Epub 2012 Feb 14.
• [13] Dioscin promotes osteoblastic proliferation and differentiation via Lrp5 and ER pathway in mouse and human osteoblast-like cell lines. J Biomed Sci. 2014 Apr 17;21(1):30. doi: 10.1186/1423-0127-21-30.
• [14] Dioscin enhances methotrexate absorption by down-regulating MDR1 in vitro and in vivo. Toxicol Appl Pharmacol. 2014 Jun 1;277(2):146-54. doi: 10.1016/j.taap.2014.03.013. Epub 2014 Mar 26.
• [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.
• [18] 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.