Details of the Drug Combination

General Information of Drug Combination (ID: DC30W15)

• Drug Combination Name: JNK-IN-8 + Plicamycin
• Indication: Childhood T acute lymphoblastic leukemia; Status: Investigative [1]
• Component Drugs:
  JNK-IN-8 (DMLWYJB): Small molecular drug: 3D MOL is unavailable
  Plicamycin (DM7C8YV): Small molecular drug: 3D MOL is unavailable
• High-throughput Screening Result:
  Testing Cell Line: CCRF-CEM
  Zero Interaction Potency (ZIP) Score: 3.01
  Bliss Independence Score: 2.13
  Loewe Additivity Score: 0.46
  LHighest Single Agent (HSA) Score: 1.98

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	[6]

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Solid tumour/cancer	2A00-2F9Z	Withdrawn from market	[4]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	[8]

Plicamycin Interacts with 8 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	[9]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[10]
Proto-oncogene tyrosine-protein kinase Src (SRC)	OTETYX40	SRC_HUMAN	Decreases Expression	[11]
Tyrosine-protein kinase receptor UFO (AXL)	OTKA2SUX	UFO_HUMAN	Decreases Expression	[12]
Transcription factor Sp3 (SP3)	OTYDQZ1T	SP3_HUMAN	Decreases Expression	[7]
Epidermal growth factor receptor kinase substrate 8 (EPS8)	OTZ6ES6V	EPS8_HUMAN	Decreases Expression	[11]
TNFAIP3-interacting protein 1 (TNIP1)	OTRAOTEW	TNIP1_HUMAN	Decreases Expression	[13]
Sphingomyelin phosphodiesterase 3 (SMPD3)	OTHQBETH	NSMA2_HUMAN	Decreases Expression	[14]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult acute myeloid leukemia	DCR6O9H	HL-60(TB)	Investigative	[1]
Adult T acute lymphoblastic leukemia	DCQU193	MOLT-4	Investigative	[1]
Chronic myelogenous leukemia	DC4Z994	K-562	Investigative	[1]
Clear cell renal cell carcinoma	DCQBYA6	CAKI-1	Investigative	[1]
Plasma cell myeloma	DC13VM3	RPMI-8226	Investigative	[1]
Renal cell carcinoma	DC73RRS	UO-31	Investigative	[1]
Breast adenocarcinoma	DCJ5VQZ	MDA-MB-468	Investigative	[15]
Carcinoma	DC538EX	RXF 393	Investigative	[15]
Colon adenocarcinoma	DCQBZ79	COLO 205	Investigative	[15]
Invasive ductal carcinoma	DCIVFS0	BT-549	Investigative	[15]
Invasive ductal carcinoma	DC0A5GT	HS 578T	Investigative	[15]
Adenocarcinoma	DCVX36Z	DU-145	Investigative	[16]
Adenocarcinoma	DCT42ZG	HCT116	Investigative	[16]
Amelanotic melanoma	DC3SVAY	M14	Investigative	[16]
Large cell lung carcinoma	DCM6G76	NCI-H460	Investigative	[16]
Lung adenocarcinoma	DC426J8	EKVX	Investigative	[16]
Lung adenocarcinoma	DC28G73	NCI-H522	Investigative	[16]
Malignant melanoma	DCDRL8M	UACC62	Investigative	[16]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
• [2] Discovery of potent and selective covalent inhibitors of JNK. Chem Biol. 2012 Jan 27;19(1):140-54.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] 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: 8394).
• [5] The Pluripotency Factor Musashi-2 Is a Novel Target for Lung Cancer Therapy.Ann Am Thorac Soc. 2018 Apr;15(Supplement_2):S124.
• [6] A H2AX?CARP-1 Interaction Regulates Apoptosis Signaling Following DNA Damage. Cancers (Basel). 2019 Feb 14;11(2):221. doi: 10.3390/cancers11020221.
• [7] The activity of a novel mithramycin analog is related to its binding to DNA, cellular accumulation, and inhibition of Sp1-driven gene transcription. Chem Biol Interact. 2014 Aug 5;219:123-32. doi: 10.1016/j.cbi.2014.05.019. Epub 2014 Jun 4.
• [8] Role of magnesium ion in mithramycin-DNA interaction: binding of mithramycin-Mg2+ complexes with DNA. Biochemistry. 1995 Jan 31;34(4):1376-85.
• [9] SP1 and SP3 mediate progesterone-dependent induction of the 17beta hydroxysteroid dehydrogenase type 2 gene in human endometrium. Biol Reprod. 2006 Oct;75(4):605-14.
• [10] Molecular mechanisms of transactivation and doxorubicin-mediated repression of survivin gene in cancer cells. J Biol Chem. 2007 Jan 26;282(4):2615-25. doi: 10.1074/jbc.M606203200. Epub 2006 Nov 22.
• [11] Mithramycin inhibits human epithelial carcinoma cell proliferation and migration involving downregulation of Eps8 expression. Chem Biol Interact. 2010 Jan 5;183(1):181-6. doi: 10.1016/j.cbi.2009.09.018.
• [12] The human receptor tyrosine kinase Axl gene--promoter characterization and regulation of constitutive expression by Sp1, Sp3 and CpG methylation. Biosci Rep. 2008 Jun;28(3):161-76. doi: 10.1042/BSR20080046.
• [13] 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.
• [14] 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.
• [15] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1126165
• [16] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976