Details of the Drug Combination

General Information of Drug Combination (ID: DCERGI0)

• Drug Combination Name: MLN8237 + IMD-0354
• Indication: Diffuse intrinsic pontine glioma; Status: Investigative [1]
• Component Drugs:
  MLN8237 (DMO8PT9): Small molecular drug
  IMD-0354 (DMOFSLE): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: SU-DIPG-XIII
  Zero Interaction Potency (ZIP) Score: 12.945
  Bliss Independence Score: 13.356
  Loewe Additivity Score: 1.131
  LHighest Single Agent (HSA) Score: 5.667

Molecular Interaction Atlas of This Drug Combination

Indication(s) of MLN8237

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 3	[2]
Small-cell lung cancer	2C25.Y	Phase 2	[3]

MLN8237 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Aurora kinase A (AURKA)	TTPS3C0	AURKA_HUMAN	Inhibitor	[5]

MLN8237 Interacts with 11 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
N-myc proto-oncogene protein (MYCN)	OTWD33K1	MYCN_HUMAN	Decreases Expression	[6]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Affects Activity	[7]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[8]
Cytochrome P450 2C8 (CYP2C8)	OTHCWT42	CP2C8_HUMAN	Affects Activity	[7]
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Affects Activity	[7]
Cytochrome P450 2C9 (CYP2C9)	OTGLBN29	CP2C9_HUMAN	Affects Activity	[7]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Affects Activity	[7]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Decreases Activity	[7]
Aurora kinase B (AURKB)	OTIY4VHU	AURKB_HUMAN	Decreases Activity	[8]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Affects Activity	[7]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Transport	[7]

Indication(s) of IMD-0354

Disease Entry	ICD 11	Status	REF
Acne vulgaris	ED80	Phase 1	[4]

IMD-0354 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Inhibitor of nuclear factor kappa-B kinase beta (IKKB)	TTJ3E9X	IKKB_HUMAN	Inhibitor	[9]

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] 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: 7790).
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] Activation of histamine H4 receptor inhibits TNFalpha/IMD-0354-induced apoptosis in human salivary NS-SV-AC cells. Apoptosis. 2014 Dec;19(12):1702-11.
• [5] Effect of Aurora A kinase inhibitor MLN8237 combined with rituximab on antitumor activity in preclinical B-cell non-Hodgkin's lymphoma models. Journal of Clinical Oncology, 2009:8553.
• [6] A Cre-conditional MYCN-driven neuroblastoma mouse model as an improved tool for preclinical studies. Oncogene. 2015 Jun;34(26):3357-68. doi: 10.1038/onc.2014.269. Epub 2014 Sep 1.
• [7] Alisertib shows negligible potential for perpetrating pharmacokinetic drug-drug interactions on ABCB1, ABCG2 and cytochromes P450, but acts as dual-activity resistance modulator through the inhibition of ABCC1 transporter. Toxicol Appl Pharmacol. 2022 Jan 1;434:115823. doi: 10.1016/j.taap.2021.115823. Epub 2021 Dec 9.
• [8] Aurora inhibitor MLN8237 in combination with docetaxel enhances apoptosis and anti-tumor activity in mantle cell lymphoma. Biochem Pharmacol. 2011 Apr 1;81(7):881-90. doi: 10.1016/j.bcp.2011.01.017. Epub 2011 Feb 1.
• [9] I B kinase beta inhibitor IMD-0354 suppresses airway remodelling in a Dermatophagoides pteronyssinus-sensitized mouse model of chronic asthma. Clin Exp Allergy. 2011 Jan;41(1):104-15.