Details of the Drug Combination

General Information of Drug Combination (ID: DCPLF0E)

Drug Combination Name

Indazole derivative 5 Bendamustine hydrochloride

Indication

Disease Entry	Status	REF
Chronic myelogenous leukemia	Investigative	[1]

Component Drugs

Indazole derivative 5 DMM1I8R

Bendamustine hydrochloride DMFH15Z

Small molecular drug

2D MOL

3D MOL

3D MOL is unavailable

High-throughput Screening Result

Testing Cell Line: K-562

Zero Interaction Potency (ZIP) Score: 6.99

Bliss Independence Score: 7.46

Loewe Additivity Score: 7.26

LHighest Single Agent (HSA) Score: 9.43

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indazole derivative 5 Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
ABL T315I mutant (ABL T315I)	TTZJTWA	ABL1_HUMAN	Inhibitor	[3]
Fusion protein Bcr-Abl T315I mutant (Bcr-Abl T315I)	TTIV39N	BCR_HUMAN-ABL1_HUMAN	Inhibitor	[3]
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Indication(s) of Bendamustine hydrochloride

Disease Entry	ICD 11	Status	REF
leukaemia	2A60-2B33	Approved	[2]

Bendamustine hydrochloride Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Modulator	[2]
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Bendamustine hydrochloride Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[5]
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Bendamustine hydrochloride Interacts with 13 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[4]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[4]
Beta-galactosidase (GLB1)	OTB0TKAG	BGAL_HUMAN	Increases Expression	[6]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[4]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[4]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[4]
Caspase-6 (CASP6)	OTXLD3EC	CASP6_HUMAN	Increases Activity	[4]
Baculoviral IAP repeat-containing protein 3 (BIRC3)	OT3E95KB	BIRC3_HUMAN	Decreases Expression	[4]
Baculoviral IAP repeat-containing protein 2 (BIRC2)	OTFXFREP	BIRC2_HUMAN	Decreases Expression	[7]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[4]
PRKC apoptosis WT1 regulator protein (PAWR)	OTKY7W52	PAWR_HUMAN	Decreases Expression	[4]
Diablo IAP-binding mitochondrial protein (DIABLO)	OTHJ9MCZ	DBLOH_HUMAN	Increases Localization	[4]
Death domain-associated protein 6 (DAXX)	OTX6O7PL	DAXX_HUMAN	Decreases Expression	[4]
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⏷ Show the Full List of 13 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult acute myeloid leukemia	DCNQXAJ	HL-60(TB)	Investigative	[1]
Adult T acute lymphoblastic leukemia	DCC2K7K	MOLT-4	Investigative	[1]
Astrocytoma	DCLKMEJ	SNB-19	Investigative	[1]
Childhood T acute lymphoblastic leukemia	DC5M0M4	CCRF-CEM	Investigative	[1]
Clear cell renal cell carcinoma	DCTVHYH	TK-10	Investigative	[1]
Clear cell renal cell carcinoma	DC7GXKQ	CAKI-1	Investigative	[1]
Renal cell carcinoma	DCSHNL2	UO-31	Investigative	[1]
Breast adenocarcinoma	DCEELBR	MDA-MB-468	Investigative	[8]
Carcinoma	DCFVNRS	MCF7	Investigative	[8]
Invasive ductal carcinoma	DC7UVX4	BT-549	Investigative	[8]
Adenocarcinoma	DCGIG35	A549	Investigative	[9]
Adenocarcinoma	DCW73IU	HCT-15	Investigative	[9]
Adenocarcinoma	DC5W7PV	HCT116	Investigative	[9]
Cutaneous melanoma	DC9ABPF	SK-MEL-28	Investigative	[9]
High grade ovarian serous adenocarcinoma	DCE7U6R	OVCAR-8	Investigative	[9]
Large cell lung carcinoma	DCAMH45	NCI-H460	Investigative	[9]
Malignant melanoma	DCYQKVK	UACC62	Investigative	[9]
Melanoma	DCOF4HC	MALME-3M	Investigative	[9]
Melanoma	DCDS81C	UACC-257	Investigative	[9]
Minimally invasive lung adenocarcinoma	DCH3PT9	NCI-H322M	Investigative	[9]
Mixed endometrioid and clear cell carcinoma	DC90OUO	IGROV1	Investigative	[9]
Prostate carcinoma	DCD2BDR	PC-3	Investigative	[9]
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⏷ Show the Full List of 22 DrugCom(s)

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	2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
3	Bcr-Abl tyrosine kinase inhibitors: a patent review.Expert Opin Ther Pat. 2015 Apr;25(4):397-412.
4	Synergistic effects of chemotherapeutic drugs in lymphoma cells are associated with down-regulation of inhibitor of apoptosis proteins (IAPs), prostate-apoptosis-response-gene 4 (Par-4), death-associated protein (Daxx) and with enforced caspase activation. Biochem Pharmacol. 2003 Sep 1;66(5):711-24. doi: 10.1016/s0006-2952(03)00410-6.
5	Pharmacokinetic and pharmacodynamic profile of bendamustine and its metabolites. Cancer Chemother Pharmacol. 2015 Jun;75(6):1143-54.
6	Chronic senescent human mesenchymal stem cells as possible contributor to the wound healing disorder after exposure to the alkylating agent sulfur mustard. Arch Toxicol. 2021 Feb;95(2):727-747. doi: 10.1007/s00204-020-02946-5. Epub 2021 Jan 25.
7	Upon drug-induced apoptosis in lymphoma cells X-linked inhibitor of apoptosis (XIAP) translocates from the cytosol to the nucleus. Leuk Lymphoma. 2004 Jul;45(7):1429-36. doi: 10.1080/1042819042000198858.
8	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.
9	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.