Details of the Drug Combination

General Information of Drug Combination (ID: DC24OZ1)

• Drug Combination Name: SNX-2112 + RTB101
• Indication: Ewing sarcoma-peripheral primitive neuroectodermal tumour; Status: Investigative [1]
• Component Drugs:
  SNX-2112 (DMB5A80): Small molecular drug
  RTB101 (DM62QTW): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: ES2
  Zero Interaction Potency (ZIP) Score: 1.79
  Bliss Independence Score: 1.51
  Loewe Additivity Score: 0.45
  LHighest Single Agent (HSA) Score: 4.69

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 RTB101

Disease Entry	ICD 11	Status	REF
Respiratory tract infection	CA45	Phase 3	[3]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[4]

RTB101 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
CREB-regulated transcription coactivator 1 (TORC1)	TT4GO0F	CRTC1_HUMAN	Inhibitor	[6]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Breast and ovarian cancer syndrome	DC3JG56	UWB1289+BRCA1	Investigative	[7]
Breast carcinoma	DC2RGU3	OCUBM	Investigative	[7]
Carcinoma	DC801JN	OV90	Investigative	[7]
Carcinoma	DCCLDRK	MDAMB436	Investigative	[7]
Colon adenocarcinoma	DCQFSS3	LOVO	Investigative	[7]
Colon carcinoma	DCCQX5B	RKO	Investigative	[7]
Invasive ductal carcinoma	DC0FJPG	T-47D	Investigative	[7]
Rectal adenocarcinoma	DC4TXJD	SW837	Investigative	[7]
Adenocarcinoma	DCLUOV9	CAOV3	Investigative	[8]
Adenocarcinoma	DCO48A5	A427	Investigative	[8]
Adenocarcinoma	DCKUWNC	NCIH1650	Investigative	[8]
Adenocarcinoma	DCHYKY9	NCIH2122	Investigative	[8]
Adenocarcinoma	DCKCJYE	NCIH520	Investigative	[8]
Adenocarcinoma	DCA1EJW	DLD1	Investigative	[8]
Adenocarcinoma	DCBBXWJ	HCT116	Investigative	[8]
Adenocarcinoma	DC5D886	HT29	Investigative	[8]
Adenocarcinoma	DC7KLTO	SW-620	Investigative	[8]
Amelanotic melanoma	DC0OURA	A2058	Investigative	[8]
Germ cell tumour	DCXS1QQ	PA1	Investigative	[8]
Large cell lung carcinoma	DCQ0USO	NCI-H460	Investigative	[8]
Malignant melanoma	DCPHVNA	A375	Investigative	[8]
Malignant melanoma	DCNOMJ4	HT144	Investigative	[8]
Malignant melanoma	DCBJX51	RPMI7951	Investigative	[8]
Malignant melanoma	DC7881Q	SKMEL30	Investigative	[8]
Malignant melanoma	DC65VHH	UACC62	Investigative	[8]
Mesothelioma	DCASNR4	MSTO	Investigative	[8]
Non small cell carcinoma	DCER53Z	SKMES1	Investigative	[8]
Ovarian endometrioid adenocarcinoma	DCEC3K1	A2780	Investigative	[8]
Ovarian serous cystadenocarcinoma	DC9HIBF	SK-OV-3	Investigative	[8]
Prostate carcinoma	DCMSZZQ	LNCAP	Investigative	[8]

References

• [1] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [2] Heat shock protein 90: inhibitors in clinical trials. J Med Chem. 2010 Jan 14;53(1):3-17.
• [3] ClinicalTrials.gov (NCT04139915) Effect of RTB101 on Illness Associated With Respiratory Tract Infections in the Elderly. U.S. National Institutes of Health.
• [4] ClinicalTrials.gov (NCT04409327) Phase 2 Study to Determine if RTB101 Reduces the Severity of COVID-19 in Older Adults Residing in Nursing Homes. U.S. National Institutes of Health.
• [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.
• [6] Anti-ageing pipeline starts to mature.Nat Rev Drug Discov. 2018 Sep;17(9):609-612.
• [7] 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.
• [8] 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.