Details of the Drug Combination

General Information of Drug Combination (ID: DC3A9WO)

• Drug Combination Name: Tanespimycin + Ruxolitinib
• Indication: Hodgkin lymphoma; Status: Investigative [1]
• Component Drugs:
  Tanespimycin (DMNLQHK): Small molecular drug
  Ruxolitinib (DM7Q98D): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: L-1236
  Zero Interaction Potency (ZIP) Score: 17.884
  Bliss Independence Score: 20.926
  Loewe Additivity Score: 8.218
  LHighest Single Agent (HSA) Score: 10.536

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Tanespimycin

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Phase 2	[2]
Multiple myeloma	2A83	Discontinued in Phase 3	[2]

Tanespimycin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Heat shock protein 90 alpha (HSP90A)	TT78R5H	HS90A_HUMAN	Inhibitor	[12]

Tanespimycin Interacts with 52 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Receptor-type tyrosine-protein kinase FLT3 (FLT3)	OTMSRYMK	FLT3_HUMAN	Decreases Expression	[13]
Apoptotic protease-activating factor 1 (APAF1)	OTJWIVY0	APAF_HUMAN	Increases Expression	[14]
Protein MTSS 1 (MTSS1)	OT5DTDO2	MTSS1_HUMAN	Increases Expression	[15]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Expression	[16]
Anterior gradient protein 2 homolog (AGR2)	OTRRZT7W	AGR2_HUMAN	Increases Expression	[11]
RAF proto-oncogene serine/threonine-protein kinase (RAF1)	OT51LSFO	RAF1_HUMAN	Decreases Expression	[17]
Annexin A1 (ANXA1)	OT5OFDJC	ANXA1_HUMAN	Increases Expression	[11]
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Decreases Expression	[16]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Phosphorylation	[18]
ATP synthase subunit beta, mitochondrial (ATP5F1B)	OTLFZUQK	ATPB_HUMAN	Decreases Expression	[11]
Alpha-enolase (ENO1)	OTB1KWJS	ENOA_HUMAN	Increases Expression	[11]
L-lactate dehydrogenase B chain (LDHB)	OT9B1CT3	LDHB_HUMAN	Increases Expression	[11]
Profilin-1 (PFN1)	OTHTGA1H	PROF1_HUMAN	Increases Expression	[11]
Heat shock protein HSP 90-beta (HSP90AB1)	OTR69EG7	HS90B_HUMAN	Affects Binding	[19]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Decreases Expression	[20]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[20]
Mast/stem cell growth factor receptor Kit (KIT)	OTHUY3VZ	KIT_HUMAN	Decreases Expression	[21]
Elongation factor 2 (EEF2)	OTZ7SZ39	EF2_HUMAN	Increases Expression	[11]
Plastin-2 (LCP1)	OTK61F2A	PLSL_HUMAN	Increases Expression	[11]
Intron Large complex component GCFC2 (GCFC2)	OTC7FRXL	GCFC2_HUMAN	Increases Expression	[11]
Moesin (MSN)	OTZJ4J6G	MOES_HUMAN	Increases Expression	[11]
Elongation factor 1-gamma (EEF1G)	OTW7DH2F	EF1G_HUMAN	Decreases Expression	[11]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[22]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[22]
M-phase inducer phosphatase 3 (CDC25C)	OTPQI71S	MPIP3_HUMAN	Decreases Expression	[20]
Serine hydroxymethyltransferase, mitochondrial (SHMT2)	OT5NCAZN	GLYM_HUMAN	Decreases Expression	[11]
Heat shock 70 kDa protein 4 (HSPA4)	OT5HR0AR	HSP74_HUMAN	Increases Expression	[23]
Radixin (RDX)	OTNSYUN6	RADI_HUMAN	Increases Expression	[11]
Metalloproteinase inhibitor 3 (TIMP3)	OTDGQAD1	TIMP3_HUMAN	Increases Expression	[15]
Serpin B5 (SERPINB5)	OTSMXQRJ	SPB5_HUMAN	Increases Expression	[15]
Transcription initiation factor IIA subunit 2 (GTF2A2)	OTE5Q4OS	T2AG_HUMAN	Increases Expression	[11]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Expression	[24]
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Increases Activity	[25]
Echinoderm microtubule-associated protein-like 5 (EML5)	OT0EFCPB	EMAL5_HUMAN	Increases Expression	[11]
Protein CBFA2T1 (RUNX1T1)	OT30DED5	MTG8_HUMAN	Decreases Expression	[26]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[27]
Dehydrogenase/reductase SDR family member 2, mitochondrial (DHRS2)	OTFHWIY8	DHRS2_HUMAN	Increases Expression	[11]
Eukaryotic translation initiation factor 3 subunit I (EIF3I)	OTE07WND	EIF3I_HUMAN	Decreases Expression	[11]
Src substrate cortactin (CTTN)	OTJRG4ES	SRC8_HUMAN	Increases Expression	[11]
La-related protein 7 (LARP7)	OTLLOZTL	LARP7_HUMAN	Increases Expression	[11]
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase TPTE2 (TPTE2)	OTR3K733	TPTE2_HUMAN	Increases Expression	[11]
Potassium voltage-gated channel subfamily V member 2 (KCNV2)	OTLS8OU5	KCNV2_HUMAN	Decreases Expression	[11]
SRC kinase signaling inhibitor 1 (SRCIN1)	OTQZNQQ5	SRCN1_HUMAN	Increases Expression	[11]
Pinin (PNN)	OT0HXICH	PININ_HUMAN	Increases Expression	[15]
PRKR-interacting protein 1 (PRKRIP1)	OTNTYMW0	PKRI1_HUMAN	Increases Expression	[11]
Transcription factor COE2 (EBF2)	OTFWZE51	COE2_HUMAN	Increases Expression	[11]
Phenylalanine--tRNA ligase beta subunit (FARSB)	OT8N9TT5	SYFB_HUMAN	Increases Expression	[11]
Poly polymerase 2 (PARP2)	OTYL81ZI	PARP2_HUMAN	Increases Expression	[11]
A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1)	OTTLJH8W	ATS1_HUMAN	Increases Expression	[15]
Proliferation-associated protein 2G4 (PA2G4)	OT7IG7HT	PA2G4_HUMAN	Increases Expression	[11]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Abundance	[28]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[29]

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	[30]
Janus kinase 1 (JAK-1)	TT6DM01	JAK1_HUMAN	Modulator	[30]
Urokinase plasminogen activator surface receptor (PLAUR)	TTPRL03	UPAR_HUMAN	Inhibitor	[31]
HUMAN janus kinase 1 (JAK-1)	TTWKB01	JAK1_HUMAN	Inhibitor	[32]
HUMAN janus kinase 2 (JAK-2)	TT0F5HE	JAK2_HUMAN	Inhibitor	[32]

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	[33]

References

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• [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.
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