Details of the Drug Combination

General Information of Drug Combination (ID: DCEBHRJ)

• Drug Combination Name: Amonafide + Bendamustine hydrochloride
• Indication: Plasma cell myeloma; Status: Investigative [1]
• Component Drugs:
  Amonafide (DMAH59S): Small molecular drug
  Bendamustine hydrochloride (DMFH15Z): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: RPMI-8226
  Zero Interaction Potency (ZIP) Score: 6.27
  Bliss Independence Score: 6.6
  Loewe Additivity Score: 3.16
  LHighest Single Agent (HSA) Score: 13.7

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Amonafide

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Phase 3	[2]
Ovarian cancer	2C73	Phase 3	[2]
Prostate cancer	2C82.0	Phase 3	[2]

Indication(s) of Bendamustine hydrochloride

Disease Entry	ICD 11	Status	REF
leukaemia	2A60-2B33	Approved	[3]

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	[3]

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]

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]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCCBITS	A549	Investigative	[1]
Adenocarcinoma	DCTMDM4	HCT116	Investigative	[1]
Adenocarcinoma	DC57505	HCT-15	Investigative	[1]
Adenocarcinoma	DCMSDM9	HT29	Investigative	[1]
Adenocarcinoma	DCNM37B	SW-620	Investigative	[1]
Adult T acute lymphoblastic leukemia	DC87KOH	MOLT-4	Investigative	[1]
Anaplastic large cell lymphoma	DC3V0KS	SR	Investigative	[1]
Astrocytoma	DCL08FE	SNB-19	Investigative	[1]
Chronic myelogenous leukemia	DCW4XC5	K-562	Investigative	[1]
Cutaneous melanoma	DCIZEEZ	SK-MEL-28	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCTNOYZ	OVCAR-8	Investigative	[1]
Large cell lung carcinoma	DC1GN3O	NCI-H460	Investigative	[1]
Melanoma	DC3KSIT	MALME-3M	Investigative	[1]
Prostate carcinoma	DCU8B96	PC-3	Investigative	[1]
Colon adenocarcinoma	DC5J4FQ	COLO 205	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] ClinicalTrials.gov (NCT00715637) Phase III Randomized Study of Amonafide (AS1413) and Cytarabine Versus Daunorubicin and Cytarabine in Patients With Secondary Acute Myeloid Leukemia (AML)- the ACCEDEStudy. U.S. National Institutes of Health.
• [3] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [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.