Details of the Drug Combination

General Information of Drug Combination (ID: DCSWL8L)

• Drug Combination Name: SNX-2112 + Lomustine
• Indication: Adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  SNX-2112 (DMB5A80): Small molecular drug
  Lomustine (DMMWSUL): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: DLD1
  Zero Interaction Potency (ZIP) Score: 2.68
  Bliss Independence Score: 0.16
  Loewe Additivity Score: 0.15
  LHighest Single Agent (HSA) Score: 4.55

Molecular Interaction Atlas of This Drug Combination

Indication(s) of SNX-2112

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[2]

SNX-2112 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Heat shock protein 90 alpha (HSP90A)	TT78R5H	HS90A_HUMAN	Inhibitor	[2]

SNX-2112 Interacts with 14 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Inhibitor of nuclear factor kappa-B kinase subunit alpha (CHUK)	OTLF4ZB1	IKKA_HUMAN	Decreases Expression	[5]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[5]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[5]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Decreases Expression	[5]
Endoplasmin (HSP90B1)	OT02XLBR	ENPL_HUMAN	Decreases Expression	[5]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Expression	[5]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Expression	[5]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Expression	[5]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Affects Localization	[5]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Decreases Expression	[5]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[5]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[5]
Heat shock protein 75 kDa, mitochondrial (TRAP1)	OTNG0L8J	TRAP1_HUMAN	Decreases Expression	[5]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[5]

Indication(s) of Lomustine

Disease Entry	ICD 11	Status	REF
Brain cancer	2A00	Approved	[3]
Central nervous system neoplasm	N.A.	Approved	[4]
Primitive neuroectodermal tumor	N.A.	Approved	[4]
Classic Hodgkin lymphoma	N.A.	Investigative	[4]

Lomustine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Inhibitor	[6]

Lomustine Interacts with 8 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Suppressor of cytokine signaling 1 (SOCS1)	OTWA9KFU	SOCS1_HUMAN	Decreases Expression	[7]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[8]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Increases Expression	[9]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[10]
Angiotensin-converting enzyme 2 (ACE2)	OTTRZGU7	ACE2_HUMAN	Decreases Expression	[11]
DNA polymerase eta (POLH)	OTN07WXU	POLH_HUMAN	Increases Expression	[12]
Methylated-DNA--protein-cysteine methyltransferase (MGMT)	OT40A9WH	MGMT_HUMAN	Decreases Response To Substance	[13]
Stathmin (STMN1)	OTDJ4RV0	STMN1_HUMAN	Affects Response To Substance	[14]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Breast and ovarian cancer syndrome	DC891HL	UWB1289	Investigative	[15]
Breast carcinoma	DCZUIVN	OCUBM	Investigative	[15]
Invasive ductal carcinoma	DCR784D	T-47D	Investigative	[15]
Adenocarcinoma	DC8CCTB	NCIH2122	Investigative	[1]
Adenocarcinoma	DCTGYZ1	HCT116	Investigative	[1]
Amelanotic melanoma	DCVRFLD	A2058	Investigative	[1]
Malignant melanoma	DCMAJJO	SKMEL30	Investigative	[1]
Mesothelioma	DCS3PQY	MSTO	Investigative	[1]
Non small cell carcinoma	DCW9LN8	SKMES1	Investigative	[1]
Ovarian endometrioid adenocarcinoma	DC7DPJ7	A2780	Investigative	[1]
Ovarian serous cystadenocarcinoma	DC5POBB	SK-OV-3	Investigative	[1]

References

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• [2] Heat shock protein 90: inhibitors in clinical trials. J Med Chem. 2010 Jan 14;53(1):3-17.
• [3] 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: 7214).
• [4] Lomustine FDA Label
• [5] The Hsp90 inhibitor SNX-2112, induces apoptosis in multidrug resistant K562/ADR cells through suppression of Akt/NF-B and disruption of mitochondria-dependent pathways. Chem Biol Interact. 2013 Sep 5;205(1):1-10. doi: 10.1016/j.cbi.2013.06.007. Epub 2013 Jun 15.
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• [8] Enhanced in vitro invasiveness and drug resistance with altered gene expression patterns in a human lung carcinoma cell line after pulse selection with anticancer drugs. Int J Cancer. 2004 Sep 10;111(4):484-93. doi: 10.1002/ijc.20230.
• [9] High-content imaging-based BAC-GFP toxicity pathway reporters to assess chemical adversity liabilities. Arch Toxicol. 2017 Mar;91(3):1367-1383. doi: 10.1007/s00204-016-1781-0. Epub 2016 Jun 29.
• [10] Utilization of CDKN1A/p21 gene for class discrimination of DNA damage-induced clastogenicity. Toxicology. 2014 Jan 6;315:8-16. doi: 10.1016/j.tox.2013.10.009. Epub 2013 Nov 6.
• [11] Effect of common medications on the expression of SARS-CoV-2 entry receptors in liver tissue. Arch Toxicol. 2020 Dec;94(12):4037-4041. doi: 10.1007/s00204-020-02869-1. Epub 2020 Aug 17.
• [12] Translesion polymerase is upregulated by cancer therapeutics and confers anticancer drug resistance. Cancer Res. 2014 Oct 1;74(19):5585-96. doi: 10.1158/0008-5472.CAN-14-0953. Epub 2014 Aug 14.
• [13] Human osteosarcoma xenografts and their sensitivity to chemotherapy. Pathol Oncol Res. 2004;10(3):133-41. doi: 10.1007/BF03033741. Epub 2004 Sep 25.
• [14] The 1p-encoded protein stathmin and resistance of malignant gliomas to nitrosoureas. J Natl Cancer Inst. 2007 Apr 18;99(8):639-52. doi: 10.1093/jnci/djk135.
• [15] Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.