Details of the Drug Combination

General Information of Drug Combination (ID: DCUPH3G)

• Drug Combination Name: PHA-739358 + Anamorelin
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  PHA-739358 (DMGYBZI): Small molecular drug
  Anamorelin (DM6HXTS): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 11.36
  Bliss Independence Score: 11.36
  Loewe Additivity Score: 23.28
  LHighest Single Agent (HSA) Score: 23.28

Molecular Interaction Atlas of This Drug Combination

Indication(s) of PHA-739358

Disease Entry	ICD 11	Status	REF
Prostate cancer	2C82.0	Phase 2	[2]

PHA-739358 Interacts with 4 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Aurora kinase B (AURKB)	TT5LS6T	AURKB_HUMAN	Inhibitor	[4]
Aurora B messenger RNA (AURKB mRNA)	TT9RTBL	AURKB_HUMAN	Inhibitor	[5]
Aurora kinase A (AURKA)	TTPS3C0	AURKA_HUMAN	Inhibitor	[4]
Aurora kinase C (AURKC)	TTLYXIT	AURKC_HUMAN	Inhibitor	[5]

PHA-739358 Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Decreases Response To Substance	[6]

Indication(s) of Anamorelin

Disease Entry	ICD 11	Status	REF
Carbohydrate metabolism disorder	5C51.Z	Phase 3	[3]

Anamorelin Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Growth hormone secretagogue receptor 1 (GHSR)	TTWDC17	GHSR_HUMAN	Stimulator	[7]
Alpha-glucosidase (GLA)	TTHCF4J	LYAG_HUMAN; GANAB_HUMAN; GANC_HUMAN	Modulator	[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] 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: 7937).
• [3] ClinicalTrials.gov (NCT01395914) Anamorelin HCl in the Treatment of Non-Small Cell Lung Cancer-Cachexia (NSCLC-C): An Extension Study (ROMANA 3). U.S. National Institutes of Health.
• [4] Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
• [5] Potent and selective Aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition. J Med Chem. 2005 Apr 21;48(8):3080-4.
• [6] Abcg2 overexpression represents a novel mechanism for acquired resistance to the multi-kinase inhibitor Danusertib in BCR-ABL-positive cells in vitro. PLoS One. 2011 Apr 26;6(4):e19164. doi: 10.1371/journal.pone.0019164.
• [7] Pharmacodynamic hormonal effects of anamorelin, a novel oral ghrelin mimetic and growth hormone secretagogue in healthy volunteers. Growth Horm IGF Res. 2009 Jun;19(3):267-73.
• [8] Absorption, elimination, and metabolism of CS-1036, a novel -amylase inhibitor in rats and monkeys, and the relationship between gastrointestinal distribution and suppression of glucose absorption.Drug Metab Dispos.2013 Apr;41(4):878-87.