Details of the Drug Combination

General Information of Drug Combination (ID: DC0ZE8H)

Drug Combination Name
Nintedanib Steroid derivative 1
Indication
Disease Entry Status REF
Ewing sarcoma Investigative [1]
Component Drugs Nintedanib   DMMQ2OW Steroid derivative 1   DMB0NVQ
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: TC-71
Zero Interaction Potency (ZIP) Score: 14.534
Bliss Independence Score: 20.72
Loewe Additivity Score: 1.563
LHighest Single Agent (HSA) Score: 6.065

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Nintedanib
Disease Entry ICD 11 Status REF
Idiopathic pulmonary fibrosis CB03.4 Approved [2]
Non-small-cell lung cancer 2C25.Y Approved [3]
Ovarian neoplasm N.A. Approved [3]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2 [4]
Steroid derivative 1 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Hypoxia-inducible factor 1 (HIF-1) TTUX68I NOUNIPROTAC Inhibitor [9]
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Steroid derivative 1 Interacts with 8 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Expression [10]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [10]
G1/S-specific cyclin-D3 (CCND3) OTNKPQ22 CCND3_HUMAN Decreases Expression [10]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Decreases Expression [11]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Increases Expression [10]
Bcl2-associated agonist of cell death (BAD) OT63ERYM BAD_HUMAN Decreases Phosphorylation [10]
17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2) OT3K7HY5 DHB2_HUMAN Decreases Response To Substance [12]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Increases Response To Substance [13]
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⏷ Show the Full List of 8 DOT(s)

References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
2 FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (NDA) 205832
3 Nintedanib FDA Label
4 ClinicalTrials.gov (NCT04338802) Efficacy and Safety of Nintedanib in the Treatment of Pulmonary Fibrosis in Patients With Moderate to Severe COVID -19. U.S. National Institutes of Health.
5 Estrogen effects on tubulin expression and taxane mediated cytotoxicity in prostate cancer cells. Prostate. 2005 Oct 1;65(2):141-50. doi: 10.1002/pros.20246.
6 Combination of Quercetin and 2-Methoxyestradiol Enhances Inhibition of Human Prostate Cancer LNCaP and PC-3 Cells Xenograft Tumor Growth. PLoS One. 2015 May 26;10(5):e0128277. doi: 10.1371/journal.pone.0128277. eCollection 2015.
7 2-Methoxyestradiol and paclitaxel have similar effects on the cell cycle and induction of apoptosis in prostate cancer cells. Cancer Lett. 2006 Jan 8;231(1):49-64. doi: 10.1016/j.canlet.2005.01.018.
8 Gastrointestinally distributed UDP-glucuronosyltransferase 1A10, which metabolizes estrogens and nonsteroidal anti-inflammatory drugs, depends upon phosphorylation. J Biol Chem. 2004 Jul 2;279(27):28320-9. doi: 10.1074/jbc.M401396200. Epub 2004 Apr 26.
9 Hypoxia-inducible factor (HIF) inhibitors: a patent survey (2011-2015).Expert Opin Ther Pat. 2016;26(3):309-22.
10 2-methoxyestradiol induces mitotic arrest, apoptosis, and synergistic cytotoxicity with arsenic trioxide in human urothelial carcinoma cells. PLoS One. 2013 Aug 13;8(8):e68703. doi: 10.1371/journal.pone.0068703. eCollection 2013.
11 Arsenic trioxide and 2-methoxyestradiol reduce beta-catenin accumulation after proteasome inhibition and enhance the sensitivity of myeloma cells to Bortezomib. Leuk Res. 2008 Nov;32(11):1674-83. doi: 10.1016/j.leukres.2008.03.039. Epub 2008 May 15.
12 The role of 17beta-hydroxysteroid dehydrogenases in modulating the activity of 2-methoxyestradiol in breast cancer cells. Cancer Res. 2006 Jan 1;66(1):324-30. doi: 10.1158/0008-5472.CAN-05-2391.
13 Acquisition of resistance of pancreatic cancer cells to 2-methoxyestradiol is associated with the upregulation of manganese superoxide dismutase. Mol Cancer Res. 2012 Jun;10(6):768-77. doi: 10.1158/1541-7786.MCR-11-0378. Epub 2012 Apr 30.