Details of the Drug Combination

General Information of Drug Combination (ID: DCNUH3W)

• Drug Combination Name: Arfolitixorin + Plicamycin
• Indication: Adult acute myeloid leukemia; Status: Investigative [1]
• Component Drugs:
  Arfolitixorin (DMIXMYK): Small molecular drug
  Plicamycin (DM7C8YV): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HL-60(TB)
  Zero Interaction Potency (ZIP) Score: 8.2
  Bliss Independence Score: 6.89
  Loewe Additivity Score: 2.9
  LHighest Single Agent (HSA) Score: 7.8

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Arfolitixorin

Disease Entry	ICD 11	Status	REF
Colorectal cancer	2B91.Z	Phase 3	[2]

Indication(s) of Plicamycin

Disease Entry	ICD 11	Status	REF
Hypercalcaemia	5B91.0	Approved	[3]
Testicular cancer	2C80	Approved	[3]
Solid tumour/cancer	2A00-2F9Z	Withdrawn from market	[4]
Lung cancer	2C25.0	Investigative	[5]
Ovarian cancer	2C73	Investigative	[5]

Plicamycin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
RNA synthesis (hRNA synth)	TTX2AYW	NOUNIPROTAC	Modulator	[7]

Plicamycin Interacts with 16 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2)	OT3K7HY5	DHB2_HUMAN	Decreases Expression	[8]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Expression	[9]
Aryl hydrocarbon receptor (AHR)	OTFE4EYE	AHR_HUMAN	Decreases Expression	[9]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Expression	[9]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[10]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Activity	[10]
Epoxide hydrolase 1 (EPHX1)	OTBKWQER	HYEP_HUMAN	Decreases Expression	[11]
Transcription factor Sp1 (SP1)	OTISPT4X	SP1_HUMAN	Decreases Expression	[6]
Proto-oncogene tyrosine-protein kinase Src (SRC)	OTETYX40	SRC_HUMAN	Decreases Expression	[12]
Tissue factor (F3)	OT3MSU3B	TF_HUMAN	Decreases Expression	[13]
Tyrosine-protein kinase receptor UFO (AXL)	OTKA2SUX	UFO_HUMAN	Decreases Expression	[14]
Transcription factor Sp3 (SP3)	OTYDQZ1T	SP3_HUMAN	Decreases Expression	[6]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Decreases Expression	[15]
Epidermal growth factor receptor kinase substrate 8 (EPS8)	OTZ6ES6V	EPS8_HUMAN	Decreases Expression	[12]
TNFAIP3-interacting protein 1 (TNIP1)	OTRAOTEW	TNIP1_HUMAN	Decreases Expression	[16]
Sphingomyelin phosphodiesterase 3 (SMPD3)	OTHQBETH	NSMA2_HUMAN	Decreases Expression	[17]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult T acute lymphoblastic leukemia	DCHQNJA	MOLT-4	Investigative	[1]
Astrocytoma	DCAX9WE	U251	Investigative	[1]
Chronic myelogenous leukemia	DCJIOHM	K-562	Investigative	[1]
Clear cell renal cell carcinoma	DCXGX2G	A498	Investigative	[1]
Clear cell renal cell carcinoma	DCE48U2	CAKI-1	Investigative	[1]
Glioblastoma	DCU3RMA	SNB-75	Investigative	[1]
Glioma	DC0BYLO	SF-268	Investigative	[1]
Glioma	DCBTP00	SF-539	Investigative	[1]
Plasma cell myeloma	DCPNN7J	RPMI-8226	Investigative	[1]
Breast adenocarcinoma	DCLVOLC	MDA-MB-468	Investigative	[18]
Carcinoma	DCLR5YE	RXF 393	Investigative	[18]
Colon carcinoma	DC114D2	KM12	Investigative	[18]
Invasive ductal carcinoma	DC9HH1T	BT-549	Investigative	[18]
Invasive ductal carcinoma	DCQ0CNF	HS 578T	Investigative	[18]
Adenocarcinoma	DC9CFYG	OVCAR3	Investigative	[19]
Adenocarcinoma	DCCUG75	A549	Investigative	[19]
Adenocarcinoma	DCGN1ZC	HCT116	Investigative	[19]
Adenocarcinoma	DCPVDE6	HCC-2998	Investigative	[19]
Adenocarcinoma	DCW0WOI	HT29	Investigative	[19]
Amelanotic melanoma	DCVIR4L	MDA-MB-435	Investigative	[19]
Cutaneous melanoma	DCD67ZE	SK-MEL-28	Investigative	[19]
Cutaneous melanoma	DC2CMWL	SK-MEL-5	Investigative	[19]
High grade ovarian serous adenocarcinoma	DCXY2YC	OVCAR-4	Investigative	[19]
High grade ovarian serous adenocarcinoma	DCVHNT7	OVCAR-8	Investigative	[19]
High grade ovarian serous adenocarcinoma	DCKVOC5	OVCAR-5	Investigative	[19]
Large cell lung carcinoma	DCO9KER	NCI-H460	Investigative	[19]
Lung adenocarcinoma	DCZ136F	HOP-62	Investigative	[19]
Lung adenocarcinoma	DCJOF1H	EKVX	Investigative	[19]
Lung adenocarcinoma	DCOMOI5	MDA-MB-231	Investigative	[19]
Lung adenocarcinoma	DC5FKCX	NCI-H522	Investigative	[19]
Malignant melanoma	DC1WPAR	LOX IMVI	Investigative	[19]
Malignant melanoma	DC9EYB0	UACC62	Investigative	[19]
Melanoma	DCSEYSD	MALME-3M	Investigative	[19]
Melanoma	DC8GC5Q	UACC-257	Investigative	[19]
Melanoma	DC893YD	SK-MEL-2	Investigative	[19]
Minimally invasive lung adenocarcinoma	DCC5SVQ	NCI-H322M	Investigative	[19]
Mixed endometrioid and clear cell carcinoma	DCJ5WHD	IGROV1	Investigative	[19]
Ovarian serous cystadenocarcinoma	DCN8VSD	SK-OV-3	Investigative	[19]
Prostate carcinoma	DCUAZVC	PC-3	Investigative	[19]

References

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• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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• [15] CREB/Sp1-mediated MCL1 expression and NFB-mediated ABCB1 expression modulate the cytotoxicity of daunorubicin in chronic myeloid leukemia cells. Toxicol Appl Pharmacol. 2022 Jan 15;435:115847. doi: 10.1016/j.taap.2021.115847. Epub 2021 Dec 25.
• [16] Sp sites contribute to basal and inducible expression of the human TNIP1 (TNF-inducible protein 3-interacting protein 1) promoter. Biochem J. 2013 Jun 15;452(3):519-29. doi: 10.1042/BJ20121666.
• [17] Transcriptional regulation of neutral sphingomyelinase 2 gene expression of a human breast cancer cell line, MCF-7, induced by the anti-cancer drug, daunorubicin. Biochim Biophys Acta. 2009 Nov-Dec;1789(11-12):681-90. doi: 10.1016/j.bbagrm.2009.08.006. Epub 2009 Aug 19.
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• [19] 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.