Details of the Drug Combination

General Information of Drug Combination (ID: DC33SHL)

Drug Combination Name
Exemestane LEE011
Indication
Disease Entry Status REF
Breast Cancer Phase 1 [1]
Component Drugs Exemestane   DM9HPW3 LEE011   DMMX75K
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D 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 [6]
------------------------------------------------------------------------------------
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 [7]
------------------------------------------------------------------------------------
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 [8]
Trefoil factor 1 (TFF1) OTCYQH4F TFF1_HUMAN Increases Expression [9]
Progesterone receptor (PGR) OT0FZ3QE PRGR_HUMAN Increases Expression [9]
Myb-related protein B (MYBL2) OTZ3JX8Q MYBB_HUMAN Increases Expression [10]
Androgen receptor (AR) OTUBKAZZ ANDR_HUMAN Affects Localization [11]
Aromatase (CYP19A1) OTZ6XF74 CP19A_HUMAN Decreases Activity [12]
Amphiregulin (AREG) OTJFOR67 AREG_HUMAN Increases Expression [9]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2) OTGVC9MY PLCG2_HUMAN Increases Expression [10]
Homeobox protein Hox-D11 (HOXD11) OT9XGA4G HXD11_HUMAN Increases Expression [10]
Pituitary adenylate cyclase-activating polypeptide type I receptor (ADCYAP1R1) OTNBHULA PACR_HUMAN Increases Expression [10]
Proliferation marker protein Ki-67 (MKI67) OTA8N1QI KI67_HUMAN Decreases Expression [13]
Kallikrein-7 (KLK7) OTIWGMO2 KLK7_HUMAN Increases Expression [10]
Disabled homolog 2 (DAB2) OTRMQTMZ DAB2_HUMAN Increases Expression [10]
CD83 antigen (CD83) OT1V4WQF CD83_HUMAN Increases Expression [10]
Unconventional myosin-IXb (MYO9B) OTQ94R5K MYO9B_HUMAN Increases Expression [10]
RRP12-like protein (RRP12) OTQQAEH4 RRP12_HUMAN Increases Expression [10]
Dynein axonemal assembly factor 9 (DNAAF9) OTTKWWQU DAAF9_HUMAN Increases Expression [10]
E3 ubiquitin-protein ligase RNF123 (RNF123) OTL59S8J RN123_HUMAN Increases Expression [10]
Osteopetrosis-associated transmembrane protein 1 (OSTM1) OTKNJDH7 OSTM1_HUMAN Increases Expression [10]
Glypican-2 (GPC2) OT3WSQE1 GPC2_HUMAN Increases Expression [10]
Tumor necrosis factor receptor superfamily member 14 (TNFRSF14) OTB82PFO TNR14_HUMAN Increases Expression [10]
Integrator complex subunit 4 (INTS4) OT5JQ913 INT4_HUMAN Increases Expression [10]
Inositol polyphosphate 5-phosphatase K (INPP5K) OTQFLQKA INP5K_HUMAN Increases Expression [10]
ATP-binding cassette sub-family G member 4 (ABCG4) OT2XJIOG ABCG4_HUMAN Increases Expression [10]
TRIO and F-actin-binding protein (TRIOBP) OTGB5WHC TARA_HUMAN Increases Expression [10]
TBC1 domain family member 17 (TBC1D17) OT75ZWLB TBC17_HUMAN Increases Expression [10]
Kinesin-like protein KIF13B (KIF13B) OTAFS1YV KI13B_HUMAN Increases Expression [10]
Transcription factor COE1 (EBF1) OTZ61YYH COE1_HUMAN Increases Expression [10]
Meteorin (METRN) OTI2645G METRN_HUMAN Increases Expression [10]
Solute carrier family 13 member 4 (SLC13A4) OTP3N8N3 S13A4_HUMAN Increases Expression [10]
------------------------------------------------------------------------------------
⏷ Show the Full List of 30 DOT(s)
Indication(s) of LEE011
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Phase 3 [4]
Solid tumour/cancer 2A00-2F9Z Phase 3 [5]
LEE011 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Cyclin-dependent kinase 4 (CDK4) TT0PG8F CDK4_HUMAN Modulator [14]
Cyclin-dependent kinase 6 (CDK6) TTO0FDJ CDK6_HUMAN Modulator [14]
------------------------------------------------------------------------------------
LEE011 Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [15]
------------------------------------------------------------------------------------

References

1 ClinicalTrials.gov (NCT01857193) Phase Ib Trial of LEE011 With Everolimus (RAD001) and Exemestane in the Treatment of Hormone Receptor Positive HER2 Negative Advanced Breast Cancer
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 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 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: 7383).
6 Aromatase inhibitors--theoretical concept and present experiences in the treatment of endometriosis. Zentralbl Gynakol. 2003 Jul-Aug;125(7-8):247-51.
7 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.
8 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.
9 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.
10 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.
11 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.
12 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.
13 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.
14 Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res. 2013 Nov 15;19(22):6173-82.
15 Cytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat and human hepatocytes. Toxicol Lett. 2018 Jul;291:138-148. doi: 10.1016/j.toxlet.2018.04.010. Epub 2018 Apr 12.