Details of the Drug Combination

General Information of Drug Combination (ID: DCRFPN0)

• Drug Combination Name: SAG + Ruxolitinib
• Indication: Hodgkin lymphoma; Status: Investigative [1]
• Component Drugs:
  SAG (DMHOG7W): Small molecular drug
  Ruxolitinib (DM7Q98D): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HDLM-2
  Zero Interaction Potency (ZIP) Score: 12.11
  Bliss Independence Score: 16.327
  Loewe Additivity Score: 11.835
  LHighest Single Agent (HSA) Score: 12.314

Molecular Interaction Atlas of This Drug Combination

Indication(s) of SAG

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[2]

SAG Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Short transient receptor potential channel 2 (TRPC2)	TTSJ9E7	Q3C1U7_HUMAN	Activator	[9]
Short transient receptor potential channel 6 (TRPC6)	TTRBT3W	TRPC6_HUMAN	Activator	[10]

SAG Interacts with 4 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Zinc finger protein GLI1 (GLI1)	OT1BTAJO	GLI1_HUMAN	Increases Expression	[11]
Paired box protein Pax-6 (PAX6)	OTOC9876	PAX6_HUMAN	Increases Expression	[11]
Isocitrate dehydrogenase , mitochondrial (IDH2)	OTTQA4PB	IDHP_HUMAN	Increases Expression	[11]
Sonic hedgehog protein (SHH)	OTOG2BXF	SHH_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	[12]
Janus kinase 1 (JAK-1)	TT6DM01	JAK1_HUMAN	Modulator	[12]
Urokinase plasminogen activator surface receptor (PLAUR)	TTPRL03	UPAR_HUMAN	Inhibitor	[13]
HUMAN janus kinase 1 (JAK-1)	TTWKB01	JAK1_HUMAN	Inhibitor	[14]
HUMAN janus kinase 2 (JAK-2)	TT0F5HE	JAK2_HUMAN	Inhibitor	[14]

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	[15]

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: 2437).
• [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] A diacylglycerol-gated cation channel in vomeronasal neuron dendrites is impaired in TRPC2 mutant mice: mechanism of pheromone transduction. Neuron. 2003 Oct 30;40(3):551-61.
• [10] Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. Nature. 1999 Jan 21;397(6716):259-63.
• [11] Differential role of Pax6 and its interaction with Shh-Gli1-IDH2 axis in regulation of glioma growth and chemoresistance. J Biochem Mol Toxicol. 2023 Feb;37(2):e23241. doi: 10.1002/jbt.23241. Epub 2022 Oct 7.
• [12] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [13] Urokinase-type plasminogen activator receptor signaling is critical in nasopharyngeal carcinoma cell growth and metastasis.Cell Cycle. 2014;13(12):1958-69.
• [14] 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.
• [15] 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.