Details of the Drug Combination

General Information of Drug Combination (ID: DC1KDX3)

Drug Combination Name
Exemestane Bosutinib
Indication
Disease Entry Status REF
Advanced Breast Cancer Phase 1 [1]
Component Drugs Exemestane   DM9HPW3 Bosutinib   DMTI8YE
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]
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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]
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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]
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⏷ Show the Full List of 30 DOT(s)
Indication(s) of Bosutinib
Disease Entry ICD 11 Status REF
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive N.A. Approved [4]
Breast cancer 2C60-2C65 Approved [5]
Bosutinib Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Tyrosine-protein kinase ABL1 (ABL) TT3PJMV ABL1_HUMAN Inhibitor [14]
Proto-oncogene c-Src (SRC) TT6PKBN SRC_HUMAN Inhibitor [14]
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Bosutinib Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [15]
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Bosutinib 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]
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Bosutinib Interacts with 6 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Proto-oncogene tyrosine-protein kinase Src (SRC) OTETYX40 SRC_HUMAN Decreases Phosphorylation [17]
Tyrosine-protein kinase ABL1 (ABL1) OT09YVXH ABL1_HUMAN Decreases Activity [18]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Affects Activity [19]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [20]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [17]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Decreases Phosphorylation [17]
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⏷ Show the Full List of 6 DOT(s)

References

1 ClinicalTrials.gov (NCT00793546) Study Evaluating Bosutinib-Exemestane Combination Vs Exemestane Alone in Post Menopausal Women With 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 Bosutinib FDA Label
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: 5710).
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 A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
15 In vitro and in vivo identification of ABCB1 as an efflux transporter of bosutinib. J Hematol Oncol. 2015 Jul 7;8:81.
16 In vitro assessment of time-dependent inhibitory effects on CYP2C8 and CYP3A activity by fourteen protein kinase inhibitors. Drug Metab Dispos. 2014 Jul;42(7):1202-9.
17 SKI-606 decreases growth and motility of colorectal cancer cells by preventing pp60(c-Src)-dependent tyrosine phosphorylation of beta-catenin and its nuclear signaling. Cancer Res. 2006 Feb 15;66(4):2279-86. doi: 10.1158/0008-5472.CAN-05-2057.
18 In vitro and in vivo activity of SKI-606, a novel Src-Abl inhibitor, against imatinib-resistant Bcr-Abl+ neoplastic cells. Cancer Res. 2006 Dec 1;66(23):11314-22. doi: 10.1158/0008-5472.CAN-06-1199. Epub 2006 Nov 17.
19 Identification of environmental chemicals that activate p53 signaling after in vitro metabolic activation. Arch Toxicol. 2022 Jul;96(7):1975-1987. doi: 10.1007/s00204-022-03291-5. Epub 2022 Apr 18.
20 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.