Details of the Drug Combination

General Information of Drug Combination (ID: DCMU8JX)

• Drug Combination Name: JNK-IN-8 + Bendamustine hydrochloride
• Indication: High grade ovarian serous adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  JNK-IN-8 (DMLWYJB): Small molecular drug: 3D MOL is unavailable
  Bendamustine hydrochloride (DMFH15Z): Small molecular drug: 3D MOL is unavailable
• High-throughput Screening Result:
  Testing Cell Line: OVCAR-4
  Zero Interaction Potency (ZIP) Score: 3.96
  Bliss Independence Score: 6.2
  Loewe Additivity Score: 3.54
  LHighest Single Agent (HSA) Score: 8.08

Molecular Interaction Atlas of This Drug Combination

Indication(s) of JNK-IN-8

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

JNK-IN-8 Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Stress-activated protein kinase JNK3 (JNK3)	TT056SO	MK10_HUMAN	Inhibitor	[2]
JNK2 messenger RNA (JNK2 mRNA)	TT3IVG2	MK09_HUMAN	Inhibitor	[2]
Stress-activated protein kinase JNK1 (JNK1)	TT0K6EO	MK08_HUMAN	Inhibitor	[2]

JNK-IN-8 Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cell division cycle and apoptosis regulator protein 1 (CCAR1)	OTUXLQZZ	CCAR1_HUMAN	Increases Expression	[4]

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	[6]

Bendamustine hydrochloride Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[5]
Baculoviral IAP repeat-containing protein 3 (BIRC3)	OT3E95KB	BIRC3_HUMAN	Decreases Expression	[5]
Baculoviral IAP repeat-containing protein 2 (BIRC2)	OTFXFREP	BIRC2_HUMAN	Decreases Expression	[7]
PRKC apoptosis WT1 regulator protein (PAWR)	OTKY7W52	PAWR_HUMAN	Decreases Expression	[5]
Diablo IAP-binding mitochondrial protein (DIABLO)	OTHJ9MCZ	DBLOH_HUMAN	Increases Localization	[5]
Death domain-associated protein 6 (DAXX)	OTX6O7PL	DAXX_HUMAN	Decreases Expression	[5]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Renal cell carcinoma	DCXGYLZ	UO-31	Investigative	[8]
Adenocarcinoma	DCNQBGM	A549	Investigative	[1]
Adenocarcinoma	DCLRRNL	HCT116	Investigative	[1]
Large cell lung carcinoma	DCKOYSQ	NCI-H460	Investigative	[1]
Melanoma	DC3HV3Y	MALME-3M	Investigative	[1]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976
• [2] Discovery of potent and selective covalent inhibitors of JNK. Chem Biol. 2012 Jan 27;19(1):140-54.
• [3] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [4] A H2AX?CARP-1 Interaction Regulates Apoptosis Signaling Following DNA Damage. Cancers (Basel). 2019 Feb 14;11(2):221. doi: 10.3390/cancers11020221.
• [5] 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.
• [6] Pharmacokinetic and pharmacodynamic profile of bendamustine and its metabolites. Cancer Chemother Pharmacol. 2015 Jun;75(6):1143-54.
• [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] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966