Details of the Drug Combination

General Information of Drug Combination (ID: DC267XW)

• Drug Combination Name: Ruxolitinib + Exemestane
• Indication: Estrogen-receptor Positive Invasive Metastatic Breast Cancer; Status: Phase 1 [1]
• Component Drugs:
  Ruxolitinib (DM7Q98D): Small molecular drug
  Exemestane (DM9HPW3): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Ruxolitinib

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

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	[10]
Janus kinase 1 (JAK-1)	TT6DM01	JAK1_HUMAN	Modulator	[10]
Urokinase plasminogen activator surface receptor (PLAUR)	TTPRL03	UPAR_HUMAN	Inhibitor	[11]
HUMAN janus kinase 1 (JAK-1)	TTWKB01	JAK1_HUMAN	Inhibitor	[12]
HUMAN janus kinase 2 (JAK-2)	TT0F5HE	JAK2_HUMAN	Inhibitor	[12]

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	[13]

Indication(s) of Exemestane

Disease Entry	ICD 11	Status	REF
Hormonally-responsive breast cancer	2C60-2C65	Approved	[8]
Male breast carcinoma	N.A.	Investigative	[9]

Exemestane Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Aromatase (CYP19A1)	TTSZLWK	CP19A_HUMAN	Inhibitor	[14]

Exemestane Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[15]

Exemestane Interacts with 30 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Adenylate kinase isoenzyme 1 (AK1)	OT614AR3	KAD1_HUMAN	Increases ADR	[13]
Trefoil factor 1 (TFF1)	OTCYQH4F	TFF1_HUMAN	Increases Expression	[16]
Progesterone receptor (PGR)	OT0FZ3QE	PRGR_HUMAN	Increases Expression	[16]
Myb-related protein B (MYBL2)	OTZ3JX8Q	MYBB_HUMAN	Increases Expression	[17]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Affects Localization	[18]
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Activity	[19]
Amphiregulin (AREG)	OTJFOR67	AREG_HUMAN	Increases Expression	[16]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2)	OTGVC9MY	PLCG2_HUMAN	Increases Expression	[17]
Homeobox protein Hox-D11 (HOXD11)	OT9XGA4G	HXD11_HUMAN	Increases Expression	[17]
Pituitary adenylate cyclase-activating polypeptide type I receptor (ADCYAP1R1)	OTNBHULA	PACR_HUMAN	Increases Expression	[17]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Decreases Expression	[20]
Kallikrein-7 (KLK7)	OTIWGMO2	KLK7_HUMAN	Increases Expression	[17]
Disabled homolog 2 (DAB2)	OTRMQTMZ	DAB2_HUMAN	Increases Expression	[17]
CD83 antigen (CD83)	OT1V4WQF	CD83_HUMAN	Increases Expression	[17]
Unconventional myosin-IXb (MYO9B)	OTQ94R5K	MYO9B_HUMAN	Increases Expression	[17]
RRP12-like protein (RRP12)	OTQQAEH4	RRP12_HUMAN	Increases Expression	[17]
Dynein axonemal assembly factor 9 (DNAAF9)	OTTKWWQU	DAAF9_HUMAN	Increases Expression	[17]
E3 ubiquitin-protein ligase RNF123 (RNF123)	OTL59S8J	RN123_HUMAN	Increases Expression	[17]
Osteopetrosis-associated transmembrane protein 1 (OSTM1)	OTKNJDH7	OSTM1_HUMAN	Increases Expression	[17]
Glypican-2 (GPC2)	OT3WSQE1	GPC2_HUMAN	Increases Expression	[17]
Tumor necrosis factor receptor superfamily member 14 (TNFRSF14)	OTB82PFO	TNR14_HUMAN	Increases Expression	[17]
Integrator complex subunit 4 (INTS4)	OT5JQ913	INT4_HUMAN	Increases Expression	[17]
Inositol polyphosphate 5-phosphatase K (INPP5K)	OTQFLQKA	INP5K_HUMAN	Increases Expression	[17]
ATP-binding cassette sub-family G member 4 (ABCG4)	OT2XJIOG	ABCG4_HUMAN	Increases Expression	[17]
TRIO and F-actin-binding protein (TRIOBP)	OTGB5WHC	TARA_HUMAN	Increases Expression	[17]
TBC1 domain family member 17 (TBC1D17)	OT75ZWLB	TBC17_HUMAN	Increases Expression	[17]
Kinesin-like protein KIF13B (KIF13B)	OTAFS1YV	KI13B_HUMAN	Increases Expression	[17]
Transcription factor COE1 (EBF1)	OTZ61YYH	COE1_HUMAN	Increases Expression	[17]
Meteorin (METRN)	OTI2645G	METRN_HUMAN	Increases Expression	[17]
Solute carrier family 13 member 4 (SLC13A4)	OTP3N8N3	S13A4_HUMAN	Increases Expression	[17]

References

• [1] ClinicalTrials.gov (NCT01594216) Ruxolitinib in Estrogen Receptor Positive Breast Cancer
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [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: 5688).
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] Ruxolitinib FDA Label
• [6] Incyte begins Phase III trial of ruxolitinib to treat Covid-19. 20.April.2020.
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] 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: 7073).
• [9] Exemestane FDA Label
• [10] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [11] Urokinase-type plasminogen activator receptor signaling is critical in nasopharyngeal carcinoma cell growth and metastasis.Cell Cycle. 2014;13(12):1958-69.
• [12] 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.
• [13] 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.
• [14] Aromatase inhibitors--theoretical concept and present experiences in the treatment of endometriosis. Zentralbl Gynakol. 2003 Jul-Aug;125(7-8):247-51.
• [15] In vitro metabolism of exemestane by hepatic cytochrome P450s: impact of nonsynonymous polymorphisms on formation of the active metabolite 17beta-dihydroexemestane. Pharmacol Res Perspect. 2017 Apr 27;5(3):e00314.
• [16] Characterization of the weak estrogen receptor alpha agonistic activity of exemestane. Breast Cancer Res Treat. 2009 Aug;116(3):461-70. doi: 10.1007/s10549-008-0151-x. Epub 2008 Aug 3.
• [17] Effects of aromatase inhibitors on human osteoblast and osteoblast-like cells: a possible androgenic bone protective effects induced by exemestane. Bone. 2007 Apr;40(4):876-87. doi: 10.1016/j.bone.2006.11.029. Epub 2006 Dec 28.
• [18] Identifying environmental chemicals as agonists of the androgen receptor by using a quantitative high-throughput screening platform. Toxicology. 2017 Jun 15;385:48-58. doi: 10.1016/j.tox.2017.05.001. Epub 2017 May 4.
• [19] Aromatase inhibition: translation into a successful therapeutic approach. Clin Cancer Res. 2005 Apr 15;11(8):2809-21. doi: 10.1158/1078-0432.CCR-04-2187.
• [20] Aromatase inhibitors: cellular and molecular effects. J Steroid Biochem Mol Biol. 2005 May;95(1-5):83-9. doi: 10.1016/j.jsbmb.2005.04.010.