Details of the Drug Combination

General Information of Drug Combination (ID: DCR7JUH)

• Drug Combination Name: JNK-IN-8 + Ixabepilone
• Indication: Adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  JNK-IN-8 (DMLWYJB): Small molecular drug
  Ixabepilone (DM2OZ3G): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HCC-2998
  Zero Interaction Potency (ZIP) Score: 0.97
  Bliss Independence Score: 1.14
  Loewe Additivity Score: 0.68
  LHighest Single Agent (HSA) Score: 2.68

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	[5]

Indication(s) of Ixabepilone

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[3]
Breast carcinoma	N.A.	Approved	[4]

Ixabepilone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tubulin (TUB)	TTML2WA	NOUNIPROTAC	Stablizer	[6]

Ixabepilone Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]

Ixabepilone Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Clear cell renal cell carcinoma	DCKKQOJ	786-0	Investigative	[9]
Glioma	DCBS631	SF-295	Investigative	[9]
Adenocarcinoma	DC98LV4	DU-145	Investigative	[1]
Adenocarcinoma	DCKEDYN	OVCAR3	Investigative	[1]
Adenocarcinoma	DCKLK19	HCT-15	Investigative	[1]
Lung adenocarcinoma	DC7RSZI	HOP-62	Investigative	[1]
Malignant melanoma	DCE5FH5	LOX IMVI	Investigative	[1]
Minimally invasive lung adenocarcinoma	DC3MQ4J	NCI-H322M	Investigative	[1]

References

• [1] 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.
• [2] Discovery of potent and selective covalent inhibitors of JNK. Chem Biol. 2012 Jan 27;19(1):140-54.
• [3] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6824).
• [4] Ixabepilone FDA Label
• [5] A H2AX?CARP-1 Interaction Regulates Apoptosis Signaling Following DNA Damage. Cancers (Basel). 2019 Feb 14;11(2):221. doi: 10.3390/cancers11020221.
• [6] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [7] Ixabepilone, a novel microtubule-targeting agent for breast cancer, is a substrate for P-glycoprotein (P-gp/MDR1/ABCB1) but not breast cancer resistance protein (BCRP/ABCG2). J Pharmacol Exp Ther. 2011 May;337(2):423-32.
• [8] The effect of ketoconazole on the pharmacokinetics and pharmacodynamics of ixabepilone: a first in class epothilone B analogue in late-phase clinical development. Clin Cancer Res. 2008 May 1;14(9):2701-9.
• [9] 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.