Details of the Drug Combination

General Information of Drug Combination (ID: DCICLPQ)

• Drug Combination Name: Anamorelin + Memantine
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Anamorelin (DM6HXTS): Small molecular drug
  Memantine (DMD9WSC): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 19.3
  Bliss Independence Score: 19.3
  Loewe Additivity Score: 32.3
  LHighest Single Agent (HSA) Score: 32.33

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Anamorelin

Disease Entry	ICD 11	Status	REF
Carbohydrate metabolism disorder	5C51.Z	Phase 3	[2]

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	[5]
Alpha-glucosidase (GLA)	TTHCF4J	LYAG_HUMAN; GANAB_HUMAN; GANC_HUMAN	Modulator	[6]

Indication(s) of Memantine

Disease Entry	ICD 11	Status	REF
Alzheimer disease	8A20	Approved	[3]
Asperger syndrome	N.A.	Approved	[4]
Glioblastoma	2A00	Approved	[4]

Memantine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
N-methyl-D-aspartate receptor (NMDAR)	TT9IK2Z	NOUNIPROTAC	Modulator	[7]

Memantine Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic cation transporter 2 (SLC22A2)	DT9IDPW	S22A2_HUMAN	Substrate	[8]

Memantine Interacts with 8 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[9]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[9]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[9]
Cyclin-dependent kinase 4 (CDK4)	OT7EP05T	CDK4_HUMAN	Increases Expression	[9]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[9]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Expression	[9]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Expression	[9]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Affects Expression	[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] 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.
• [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: 4253).
• [4] Memantine FDA Label
• [5] 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.
• [6] 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.
• [7] The NMDA receptor antagonist memantine as a symptomatological and neuroprotective treatment for Alzheimer's disease: preclinical evidence. Int J Geriatr Psychiatry. 2003 Sep;18(Suppl 1):S23-32.
• [8] Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotransmitters, amantadine, and memantine. Mol Pharmacol. 1998 Aug;54(2):342-52.
• [9] Memantine induces apoptosis and inhibits cell cycle progression in LNCaP prostate cancer cells. Hum Exp Toxicol. 2018 Sep;37(9):953-958. doi: 10.1177/0960327117747025. Epub 2017 Dec 11.