Details of the Drug Combination

General Information of Drug Combination (ID: DC3CHE1)

• Drug Combination Name: Colchicine + Ruxolitinib
• Indication: Hodgkin lymphoma; Status: Investigative [1]
• Component Drugs:
  Colchicine (DM2POTE): Small molecular drug
  Ruxolitinib (DM7Q98D): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: L-1236
  Zero Interaction Potency (ZIP) Score: 9.81
  Bliss Independence Score: 8.49
  Loewe Additivity Score: 7.14
  LHighest Single Agent (HSA) Score: 10.96

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Colchicine

Disease Entry	ICD 11	Status	REF
Acute gout flare	FA25.0	Approved	[2]
Acute gouty arthritis	FA25.0	Approved	[3]
Gout	FA25	Approved	[4]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[5]
Familial Mediterranean fever	N.A.	Investigative	[4]

Colchicine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tubulin (TUB)	TTML2WA	NOUNIPROTAC	Binder	[13]

Colchicine Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[14]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[15]

Colchicine Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[16]

Colchicine Interacts with 85 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[17]
Succinate dehydrogenase assembly factor 1, mitochondrial (SDHAF1)	OTDG5VW7	SDHF1_HUMAN	Decreases Expression	[12]
E3 ubiquitin-protein ligase TRIM38 (TRIM38)	OT6SP1M9	TRI38_HUMAN	Decreases Expression	[12]
Ectoderm-neural cortex protein 1 (ENC1)	OTJEUB6U	ENC1_HUMAN	Decreases Expression	[12]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Decreases Expression	[12]
Plexin-B2 (PLXNB2)	OT56I2VD	PLXB2_HUMAN	Decreases Expression	[12]
E3 ubiquitin-protein ligase RNF113A (RNF113A)	OTR6N7HU	R113A_HUMAN	Decreases Expression	[12]
DNA repair protein RAD51 homolog 3 (RAD51C)	OTUD6SY5	RA51C_HUMAN	Decreases Expression	[12]
TP53-regulated inhibitor of apoptosis 1 (TRIAP1)	OTEAUJXN	TRIA1_HUMAN	Decreases Expression	[12]
Dual specificity protein phosphatase 14 (DUSP14)	OTGODFCR	DUS14_HUMAN	Decreases Expression	[12]
Kinesin-like protein KIF20A (KIF20A)	OTXOQHE0	KI20A_HUMAN	Decreases Expression	[12]
CUGBP Elav-like family member 2 (CELF2)	OTLJJ4VT	CELF2_HUMAN	Increases Expression	[18]
Prothrombin (F2)	OTNFSM49	THRB_HUMAN	Affects Activity	[19]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Expression	[19]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Phosphorylation	[20]
Keratin, type I cytoskeletal 18 (KRT18)	OTVLQFIP	K1C18_HUMAN	Decreases Expression	[21]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[22]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[23]
Microtubule-associated protein 2 (MAP2)	OT6UYT3X	MTAP2_HUMAN	Decreases Expression	[24]
Cadherin-1 (CDH1)	OTFJMXPM	CADH1_HUMAN	Affects Activity	[25]
CD59 glycoprotein (CD59)	OTSUMQDH	CD59_HUMAN	Increases Mutagenesis	[26]
Tyrosine aminotransferase (TAT)	OT2CJ91O	ATTY_HUMAN	Decreases Expression	[27]
NADPH:adrenodoxin oxidoreductase, mitochondrial (FDXR)	OTPDCK1F	ADRO_HUMAN	Decreases Expression	[12]
Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2)	OTIN6G20	CPT2_HUMAN	Decreases Expression	[12]
M-phase inducer phosphatase 1 (CDC25A)	OTSLKKCO	MPIP1_HUMAN	Decreases Expression	[12]
Sodium-dependent serotonin transporter (SLC6A4)	OT6FGDLW	SC6A4_HUMAN	Decreases Expression	[24]
Replication factor C subunit 1 (RFC1)	OT3L5PK3	RFC1_HUMAN	Decreases Expression	[12]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Increases Expression	[28]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Decreases Expression	[12]
Tumor necrosis factor ligand superfamily member 9 (TNFSF9)	OTV9L89D	TNFL9_HUMAN	Decreases Expression	[12]
RNA-binding protein 34 (RBM34)	OTX3LUGI	RBM34_HUMAN	Decreases Expression	[12]
Mitogen-activated protein kinase 8 (MAPK8)	OTEREYS5	MK08_HUMAN	Increases Phosphorylation	[20]
Mitogen-activated protein kinase 9 (MAPK9)	OTCEVJ9E	MK09_HUMAN	Increases Phosphorylation	[20]
LIM/homeobox protein Lhx2 (LHX2)	OTK61NP8	LHX2_HUMAN	Decreases Expression	[12]
DNA mismatch repair protein Msh6 (MSH6)	OT46FP09	MSH6_HUMAN	Decreases Expression	[12]
RecQ-like DNA helicase BLM (BLM)	OTEJOAJX	BLM_HUMAN	Decreases Expression	[12]
Ataxin-1 (ATXN1)	OTQF0HNR	ATX1_HUMAN	Decreases Expression	[12]
Ras-related protein Rap-2b (RAP2B)	OTD2NDQP	RAP2B_HUMAN	Decreases Expression	[12]
Protein BTG1 (BTG1)	OTVJ2CDM	BTG1_HUMAN	Decreases Expression	[12]
Protein BTG2 (BTG2)	OTZF6K1H	BTG2_HUMAN	Decreases Expression	[12]
Transcription factor E2F1 (E2F1)	OTLKYBBC	E2F1_HUMAN	Decreases Expression	[12]
Myelin transcription factor 1 (MYT1)	OTC3660I	MYT1_HUMAN	Increases Phosphorylation	[29]
DNA-binding protein inhibitor ID-3 (ID3)	OTUULW5Z	ID3_HUMAN	Decreases Expression	[12]
Tripartite motif-containing protein 26 (TRIM26)	OTS0DJIP	TRI26_HUMAN	Decreases Expression	[12]
E3 ubiquitin-protein ligase TRIM32 (TRIM32)	OTJOV0PG	TRI32_HUMAN	Decreases Expression	[12]
Chromatin assembly factor 1 subunit A (CHAF1A)	OTXSSY4H	CAF1A_HUMAN	Decreases Expression	[12]
Chromatin assembly factor 1 subunit B (CHAF1B)	OTOMK4KH	CAF1B_HUMAN	Decreases Expression	[12]
DNA topoisomerase 3-alpha (TOP3A)	OT3CKUI9	TOP3A_HUMAN	Decreases Expression	[12]
Oligodendrocyte transcription factor 2 (OLIG2)	OTMCN6D3	OLIG2_HUMAN	Decreases Expression	[24]
Protein BTG3 (BTG3)	OT9ANHVT	BTG3_HUMAN	Decreases Expression	[12]
Protein-tyrosine kinase 2-beta (PTK2B)	OTGAS0I8	FAK2_HUMAN	Increases Phosphorylation	[18]
Histone RNA hairpin-binding protein (SLBP)	OTVYYQRT	SLBP_HUMAN	Decreases Expression	[12]
Nuclear factor of activated T-cells, cytoplasmic 4 (NFATC4)	OTTDCUAO	NFAC4_HUMAN	Decreases Localization	[30]
Neutral amino acid transporter B(0) (SLC1A5)	OTE2H26Q	AAAT_HUMAN	Decreases Expression	[12]
E3 ubiquitin-protein ligase RNF19B (RNF19B)	OTYCWKBP	RN19B_HUMAN	Decreases Expression	[12]
Protein MCM10 homolog (MCM10)	OTV0O3JN	MCM10_HUMAN	Decreases Expression	[12]
Partner and localizer of BRCA2 (PALB2)	OT6DNDBG	PALB2_HUMAN	Decreases Expression	[12]
E3 ubiquitin-protein ligase TRIM22 (TRIM22)	OTJBLG5R	TRI22_HUMAN	Decreases Expression	[12]
Leucine-rich repeat-containing protein 47 (LRRC47)	OTSE8NAO	LRC47_HUMAN	Decreases Expression	[12]
Protein tyrosine phosphatase type IVA 1 (PTP4A1)	OTK0NFXJ	TP4A1_HUMAN	Decreases Expression	[12]
Cytochrome c oxidase assembly factor 7 (COA7)	OTRQJYL6	COA7_HUMAN	Decreases Expression	[12]
Mitochondrial potassium channel (CCDC51)	OTOJNHNA	MITOK_HUMAN	Decreases Expression	[12]
Integrator complex subunit 15 (INTS15)	OT3O4INM	INT15_HUMAN	Decreases Expression	[12]
Pleckstrin homology domain-containing family F member 1 (PLEKHF1)	OT9OL16U	PKHF1_HUMAN	Decreases Expression	[12]
Krueppel-like factor 6 (KLF6)	OTQY9S7F	KLF6_HUMAN	Increases Expression	[12]
Cell division control protein 6 homolog (CDC6)	OTX93FE7	CDC6_HUMAN	Decreases Expression	[12]
Protein orai-3 (ORAI3)	OTUP3OH3	ORAI3_HUMAN	Decreases Expression	[12]
Protein pelota homolog (PELO)	OTF3WLIM	PELO_HUMAN	Decreases Expression	[12]
TIMELESS-interacting protein (TIPIN)	OT9PZHXV	TIPIN_HUMAN	Decreases Expression	[12]
tRNA pseudouridine(38/39) synthase (PUS3)	OT6WG6M2	PUS3_HUMAN	Decreases Expression	[12]
Transmembrane protein 185B (TMEM185B)	OTGNYS0J	T185B_HUMAN	Decreases Expression	[12]
Interferon-stimulated 20 kDa exonuclease-like 2 (ISG20L2)	OT3Q11WQ	I20L2_HUMAN	Decreases Expression	[12]
GrpE protein homolog 1, mitochondrial (GRPEL1)	OT8O00YJ	GRPE1_HUMAN	Decreases Expression	[12]
p53-induced death domain-containing protein 1 (PIDD1)	OTWFM930	PIDD1_HUMAN	Decreases Expression	[12]
Fructose-2,6-bisphosphatase TIGAR (TIGAR)	OTR7NMRJ	TIGAR_HUMAN	Decreases Expression	[12]
DNA damage-inducible transcript 4 protein (DDIT4)	OTHY8SY4	DDIT4_HUMAN	Decreases Expression	[12]
Homologous-pairing protein 2 homolog (PSMC3IP)	OT9UB5UO	HOP2_HUMAN	Decreases Expression	[12]
Protein CLN8 (CLN8)	OT0D4CB5	CLN8_HUMAN	Decreases Expression	[12]
rRNA methyltransferase 2, mitochondrial (MRM2)	OTRYA1HU	MRM2_HUMAN	Decreases Expression	[12]
Frizzled-1 (FZD1)	OTZATHVS	FZD1_HUMAN	Decreases Expression	[12]
SH3 and multiple ankyrin repeat domains protein 2 (SHANK2)	OTSQTPFQ	SHAN2_HUMAN	Decreases Expression	[24]
5'-AMP-activated protein kinase subunit beta-1 (PRKAB1)	OT1OG4QZ	AAKB1_HUMAN	Decreases Expression	[12]
Pleckstrin homology-like domain family A member 3 (PHLDA3)	OTXFUDO2	PHLA3_HUMAN	Decreases Expression	[12]
Sestrin-1 (SESN1)	OTSFDZWL	SESN1_HUMAN	Decreases Expression	[12]
ATP-binding cassette sub-family A member 13 (ABCA13)	OTTHTUQN	ABCAD_HUMAN	Affects Response To Substance	[31]

Indication(s) of Ruxolitinib

Disease Entry	ICD 11	Status	REF
Essential thrombocythemia	3B63.1Z	Approved	[6]
High-risk myelofibrosis	2A20.2	Approved	[7]
Myelofibrosis	2A22	Approved	[8]
Myeloproliferative neoplasm	2A20	Approved	[9]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[10]
Pancreatic cancer	2C10	Phase 3	[7]
Atopic dermatitis	EA80	Phase 1/2	[11]
Vitiligo	ED63.0	Phase 1/2	[11]

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	[32]
Janus kinase 1 (JAK-1)	TT6DM01	JAK1_HUMAN	Modulator	[32]
Urokinase plasminogen activator surface receptor (PLAUR)	TTPRL03	UPAR_HUMAN	Inhibitor	[33]
HUMAN janus kinase 1 (JAK-1)	TTWKB01	JAK1_HUMAN	Inhibitor	[34]
HUMAN janus kinase 2 (JAK-2)	TT0F5HE	JAK2_HUMAN	Inhibitor	[34]

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	[35]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976
• [2] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (NDA) 022351
• [3] 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: 7526).
• [4] Colchicine FDA Label
• [5] ClinicalTrials.gov (NCT04322565) Colchicine Counteracting Inflammation in COVID-19 Pneumonia. U.S. National Institutes of Health.
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] 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).
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [9] Ruxolitinib FDA Label
• [10] Incyte begins Phase III trial of ruxolitinib to treat Covid-19. 20.April.2020.
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• [15] Nilotinib (AMN107, Tasigna) reverses multidrug resistance by inhibiting the activity of the ABCB1/Pgp and ABCG2/BCRP/MXR transporters. Biochem Pharmacol. 2009 Jul 15;78(2):153-61.
• [16] Colchicine down-regulates cytochrome P450 2B6, 2C8, 2C9, and 3A4 in human hepatocytes by affecting their glucocorticoid receptor-mediated regulation. Mol Pharmacol. 2003 Jul;64(1):160-9.
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• [18] Discovery of a novel compound: insight into mechanisms for acrylamide-induced axonopathy and colchicine-induced apoptotic neuronal cell death. Brain Res. 2001 Aug 3;909(1-2):8-19. doi: 10.1016/s0006-8993(01)02608-7.
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• [27] Microtubule disarray in primary cultures of human hepatocytes inhibits transcriptional activity of the glucocorticoid receptor via activation of c-jun N-terminal kinase. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2004 Dec;148(2):135-9.
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