Details of the Drug Combination

General Information of Drug Combination (ID: DCRJMFI)

Drug Combination Name

Exemestane Ridaforolimus

Indication

Disease Entry	Status	REF
Breast Neoplasms	Phase 1	[1]

Component Drugs

Exemestane DM9HPW3

Ridaforolimus DMLHEU7

Small molecular drug

2D MOL

3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Exemestane

Disease Entry	ICD 11	Status	REF
Hormonally-responsive breast cancer	2C60-2C65	Approved	[2]
Male breast carcinoma	N.A.	Investigative	[3]

Exemestane Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Aromatase (CYP19A1)	TTSZLWK	CP19A_HUMAN	Inhibitor	[5]
------------------------------------------------------------------------------------

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	[6]
------------------------------------------------------------------------------------

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	[7]
Trefoil factor 1 (TFF1)	OTCYQH4F	TFF1_HUMAN	Increases Expression	[8]
Progesterone receptor (PGR)	OT0FZ3QE	PRGR_HUMAN	Increases Expression	[8]
Myb-related protein B (MYBL2)	OTZ3JX8Q	MYBB_HUMAN	Increases Expression	[9]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Affects Localization	[10]
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Activity	[11]
Amphiregulin (AREG)	OTJFOR67	AREG_HUMAN	Increases Expression	[8]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2)	OTGVC9MY	PLCG2_HUMAN	Increases Expression	[9]
Homeobox protein Hox-D11 (HOXD11)	OT9XGA4G	HXD11_HUMAN	Increases Expression	[9]
Pituitary adenylate cyclase-activating polypeptide type I receptor (ADCYAP1R1)	OTNBHULA	PACR_HUMAN	Increases Expression	[9]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Decreases Expression	[12]
Kallikrein-7 (KLK7)	OTIWGMO2	KLK7_HUMAN	Increases Expression	[9]
Disabled homolog 2 (DAB2)	OTRMQTMZ	DAB2_HUMAN	Increases Expression	[9]
CD83 antigen (CD83)	OT1V4WQF	CD83_HUMAN	Increases Expression	[9]
Unconventional myosin-IXb (MYO9B)	OTQ94R5K	MYO9B_HUMAN	Increases Expression	[9]
RRP12-like protein (RRP12)	OTQQAEH4	RRP12_HUMAN	Increases Expression	[9]
Dynein axonemal assembly factor 9 (DNAAF9)	OTTKWWQU	DAAF9_HUMAN	Increases Expression	[9]
E3 ubiquitin-protein ligase RNF123 (RNF123)	OTL59S8J	RN123_HUMAN	Increases Expression	[9]
Osteopetrosis-associated transmembrane protein 1 (OSTM1)	OTKNJDH7	OSTM1_HUMAN	Increases Expression	[9]
Glypican-2 (GPC2)	OT3WSQE1	GPC2_HUMAN	Increases Expression	[9]
Tumor necrosis factor receptor superfamily member 14 (TNFRSF14)	OTB82PFO	TNR14_HUMAN	Increases Expression	[9]
Integrator complex subunit 4 (INTS4)	OT5JQ913	INT4_HUMAN	Increases Expression	[9]
Inositol polyphosphate 5-phosphatase K (INPP5K)	OTQFLQKA	INP5K_HUMAN	Increases Expression	[9]
ATP-binding cassette sub-family G member 4 (ABCG4)	OT2XJIOG	ABCG4_HUMAN	Increases Expression	[9]
TRIO and F-actin-binding protein (TRIOBP)	OTGB5WHC	TARA_HUMAN	Increases Expression	[9]
TBC1 domain family member 17 (TBC1D17)	OT75ZWLB	TBC17_HUMAN	Increases Expression	[9]
Kinesin-like protein KIF13B (KIF13B)	OTAFS1YV	KI13B_HUMAN	Increases Expression	[9]
Transcription factor COE1 (EBF1)	OTZ61YYH	COE1_HUMAN	Increases Expression	[9]
Meteorin (METRN)	OTI2645G	METRN_HUMAN	Increases Expression	[9]
Solute carrier family 13 member 4 (SLC13A4)	OTP3N8N3	S13A4_HUMAN	Increases Expression	[9]
------------------------------------------------------------------------------------


⏷ Show the Full List of 30 DOT(s)

Indication(s) of Ridaforolimus

Disease Entry	ICD 11	Status	REF
Sarcoma	2A60-2C35	Phase 3	[4]

Ridaforolimus Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Serine/threonine-protein kinase mTOR (mTOR)	TTCJG29	MTOR_HUMAN	Inhibitor	[13]
------------------------------------------------------------------------------------

References

1	ClinicalTrials.gov (NCT01605396) A Phase II Trial of Ridaforolimus and Exemestane, Compared to Ridaforolimus, Dalotuzumab and Exemestane in Participants With Breast Cancer (MK-8669-064). U.S. National Institutes of Health.
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: 7073).
3	Exemestane FDA Label
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: 7884).
5	Aromatase inhibitors--theoretical concept and present experiences in the treatment of endometriosis. Zentralbl Gynakol. 2003 Jul-Aug;125(7-8):247-51.
6	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.
7	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.
8	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.
9	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.
10	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.
11	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.
12	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.
13	A novel c-Met inhibitor, MK8033, synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth. Oncol Rep. 2013 May;29(5):2011-8.