Details of the Drug Combination

General Information of Drug Combination (ID: DC9ITHJ)

• Drug Combination Name: Steroid derivative 1 + OSI-906
• Indication: Ewing sarcoma; Status: Investigative [1]
• Component Drugs:
  Steroid derivative 1 (DMB0NVQ): Small molecular drug
  OSI-906 (DMHKZLF): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: TC-71
  Zero Interaction Potency (ZIP) Score: 16.895
  Bliss Independence Score: 16.011
  Loewe Additivity Score: 2.349
  LHighest Single Agent (HSA) Score: 6.693

Molecular Interaction Atlas of This Drug Combination

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	[7]

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	[8]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[8]
G1/S-specific cyclin-D3 (CCND3)	OTNKPQ22	CCND3_HUMAN	Decreases Expression	[8]
Catenin beta-1 (CTNNB1)	OTZ932A3	CTNB1_HUMAN	Decreases Expression	[9]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Increases Expression	[8]
Bcl2-associated agonist of cell death (BAD)	OT63ERYM	BAD_HUMAN	Decreases Phosphorylation	[8]
17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2)	OT3K7HY5	DHB2_HUMAN	Decreases Response To Substance	[10]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Response To Substance	[11]

Indication(s) of OSI-906

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 3	[2]

OSI-906 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Insulin-like growth factor I receptor (IGF1R)	TTHRID2	IGF1R_HUMAN	Inhibitor	[12]

OSI-906 Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
HLA class I histocompatibility antigen, alpha chain G (HLA-G)	OTMLK1KN	HLAG_HUMAN	Decreases Expression	[13]
Tumor protein 63 (TP63)	OT0WOOKQ	P63_HUMAN	Decreases Expression	[13]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
• [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: 7423).
• [3] 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.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Hypoxia-inducible factor (HIF) inhibitors: a patent survey (2011-2015).Expert Opin Ther Pat. 2016;26(3):309-22.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Imidazo[2,1-b]thiazoles: multitargeted inhibitors of both the insulin-like growth factor receptor and members of the epidermal growth factor family... Bioorg Med Chem Lett. 2010 Apr 15;20(8):2452-5.
• [13] Screening of Organophosphate Flame Retardants with Placentation-Disrupting Effects in Human Trophoblast Organoid Model and Characterization of Adverse Pregnancy Outcomes in Mice. Environ Health Perspect. 2022 May;130(5):57002. doi: 10.1289/EHP10273. Epub 2022 May 3.