General Information of Drug Combination (ID: DC0VCTF)

Drug Combination Name
Sapanisertib Doxycycline
Indication
Disease Entry Status REF
Hepatoblastoma Investigative [1]
Component Drugs Sapanisertib   DMYZFNH Doxycycline   DM7ICNU
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: HB3
Zero Interaction Potency (ZIP) Score: 7.138
Bliss Independence Score: 6.764
Loewe Additivity Score: 1.945
LHighest Single Agent (HSA) Score: 1.698

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Sapanisertib
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Phase 2 [2]
Coronavirus Disease 2019 (COVID-19) 1D6Y Investigative [3]
Sapanisertib Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
HUMAN mammalian target of rapamycin (mTOR) TT7HQAF MTOR_HUMAN Inhibitor [3]
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Indication(s) of Doxycycline
Disease Entry ICD 11 Status REF
Acne vulgaris ED80 Approved [4]
Actinomycosis N.A. Approved [4]
Acute gonococcal cervicitis N.A. Approved [4]
Acute gonococcal epididymo-orchitis N.A. Approved [4]
Advanced gum disease DA0D Approved [5]
Anthrax 1B97 Approved [4]
Bartonellosis N.A. Approved [4]
Boutonneuse fever N.A. Approved [4]
Brill-Zinsser disease N.A. Approved [4]
Bronchitis CA20 Approved [4]
Brucellosis N.A. Approved [4]
Chancroid N.A. Approved [4]
Chlamydiaceae infections N.A. Approved [4]
Chronic periodontitis DA0C.Y Approved [5]
Colorectal carcinoma N.A. Approved [4]
Cutaneous anthrax N.A. Approved [4]
Endemic typhus N.A. Approved [4]
Epidemic louse-borne typhus N.A. Approved [4]
Gastrointestinal anthrax N.A. Approved [4]
Inhalational anthrax N.A. Approved [4]
Listeriosis N.A. Approved [4]
Lymphogranuloma venereum N.A. Approved [4]
Mycoplasma pneumoniae pneumonia N.A. Approved [4]
Ornithosis N.A. Approved [4]
Q fever N.A. Approved [4]
Relapsing fever N.A. Approved [4]
Rickettsialpox N.A. Approved [4]
Rickettsiosis N.A. Approved [4]
Rocky mountain spotted fever N.A. Approved [4]
Syphilis N.A. Approved [4]
Trachoma N.A. Approved [4]
Tularemia 1B94 Approved [4]
Typhus N.A. Approved [4]
Yaws N.A. Approved [4]
Diabetic foot ulcer BD54 Phase 2 [6]
Sinusitis CA0A.Z Investigative [4]
Vibrio cholerae infection 1A00 Investigative [4]
Doxycycline Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Bacterial 30S ribosomal RNA (Bact 30S rRNA) TTOVFH2 NOUNIPROTAC Modulator [8]
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Doxycycline Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [9]
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Doxycycline Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [10]
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Doxycycline Interacts with 9 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Decreases Expression [11]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Increases Expression [7]
Aryl hydrocarbon receptor (AHR) OTFE4EYE AHR_HUMAN Increases Expression [7]
HLA class I histocompatibility antigen, B alpha chain (HLA-B) OTNXFWY2 HLAB_HUMAN Affects Expression [12]
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Decreases Activity [13]
Stromelysin-1 (MMP3) OTGBI74Z MMP3_HUMAN Decreases Activity [13]
Neutrophil collagenase (MMP8) OTZXH19L MMP8_HUMAN Decreases Activity [13]
Collagenase 3 (MMP13) OTY8BZIE MMP13_HUMAN Increases Expression [14]
TAR DNA-binding protein 43 (TARDBP) OTVOSFWW TADBP_HUMAN Decreases Expression [15]
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⏷ Show the Full List of 9 DOT(s)

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 ClinicalTrials.gov (NCT02049957) Safety and Efficacy Study of Sapanisertib in Combination With Exemestane or Fulvestrant in Postmenopausal Women With Estrogen Receptor Positive/Human Epidermal Growth Factor Receptor 2 Negative (ER+/HER2-) Metastatic Breast Cancer. U.S. National Institutes of Health.
3 Prevent COVID-19 Severity by Repurposing mTOR Inhibitors. 2 April 2020
4 Doxycycline 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: 6464).
6 ClinicalTrials.gov (NCT00764361) Safety Study of Topical Doxycycline Gel for Adult Diabetic Lower Extremity Ulcers. U.S. National Institutes of Health.
7 Aryl hydrocarbon receptor protects lung adenocarcinoma cells against cigarette sidestream smoke particulates-induced oxidative stress. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):293-301.
8 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
9 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
10 A further interaction study of quinine with clinically important drugs by human liver microsomes: determinations of inhibition constant (Ki) and type of inhibition. Eur J Drug Metab Pharmacokinet. 1999 Jul-Sep;24(3):272-8.
11 Functional and histochemical analysis of MDR3 P-glycoprotein in a tetracycline-controlled gene expression system. Eur J Med Res. 2000 Dec 29;5(12):517-22.
12 Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
13 Synthesis and in vitro evaluation of targeted tetracycline derivatives: effects on inhibition of matrix metalloproteinases. Bioorg Med Chem. 2007 Mar 15;15(6):2368-74. doi: 10.1016/j.bmc.2007.01.026. Epub 2007 Jan 19.
14 Chloramphenicol causes mitochondrial stress, decreases ATP biosynthesis, induces matrix metalloproteinase-13 expression, and solid-tumor cell invasion. Toxicol Sci. 2010 Jul;116(1):140-50. doi: 10.1093/toxsci/kfq085. Epub 2010 Mar 25.
15 A high-content screen identifies novel compounds that inhibit stress-induced TDP-43 cellular aggregation and associated cytotoxicity. J Biomol Screen. 2014 Jan;19(1):44-56. doi: 10.1177/1087057113501553. Epub 2013 Sep 9.