Details of the Drug Combination

General Information of Drug Combination (ID: DCX7EN8)

• Drug Combination Name: Pelitinib + GDC-0084
• Indication: Hodgkin lymphoma; Status: Investigative [1]
• Component Drugs:
  Pelitinib (DMIW453): Small molecular drug
  GDC-0084 (DMA9SEY): N.A.
• High-throughput Screening Result:
  Testing Cell Line: L-1236
  Zero Interaction Potency (ZIP) Score: 4.547
  Bliss Independence Score: 2.416
  Loewe Additivity Score: 0.375
  LHighest Single Agent (HSA) Score: 3.691

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Pelitinib

Disease Entry	ICD 11	Status	REF
Lymphoma	2A80-2A86	Phase 2	[2]

Pelitinib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Modulator	[4]

Pelitinib Interacts with 14 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB)	OT9RDS3H	IKKB_HUMAN	Decreases Expression	[5]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[5]
B-cell lymphoma/leukemia 10 (BCL10)	OT47MCLI	BCL10_HUMAN	Decreases Expression	[5]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Decreases Activity	[6]
Transcription factor Sp1 (SP1)	OTISPT4X	SP1_HUMAN	Decreases Activity	[5]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[5]
Cyclic AMP-dependent transcription factor ATF-1 (ATF1)	OT251CI0	ATF1_HUMAN	Decreases Expression	[5]
B-cell lymphoma 3 protein (BCL3)	OT1M5B95	BCL3_HUMAN	Decreases Expression	[5]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Increases Expression	[5]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Expression	[5]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[5]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[5]
Baculoviral IAP repeat-containing protein 1 (NAIP)	OTLA925F	BIRC1_HUMAN	Decreases Expression	[5]
Baculoviral IAP repeat-containing protein 2 (BIRC2)	OTFXFREP	BIRC2_HUMAN	Decreases Expression	[5]

Indication(s) of GDC-0084

Disease Entry	ICD 11	Status	REF
Glioblastoma of brain	2A00.00	Phase 2	[3]

GDC-0084 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
PI3-kinase gamma (PIK3CG)	TTHBTOP	PK3CG_HUMAN	Inhibitor	[7]

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] 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: 7644).
• [3] ClinicalTrials.gov (NCT03522298) Safety, Pharmacokinetics and Efficacy of Paxalisib (GDC-0084) in Newly-diagnosed Glioblastoma. U.S. National Institutes of Health.
• [4] EGFR tyrosine kinase inhibitor pelitinib regulates radiation-induced p65-dependent telomerase activation in squamous cell carcinoma.Radiat Res.2013 Mar;179(3):304-12.
• [5] Irreversible EGFR inhibitor EKB-569 targets low-LET -radiation-triggered rel orchestration and potentiates cell death in squamous cell carcinoma. PLoS One. 2011;6(12):e29705. doi: 10.1371/journal.pone.0029705. Epub 2011 Dec 29.
• [6] Cysteine mapping in conformationally distinct kinase nucleotide binding sites: application to the design of selective covalent inhibitors. J Med Chem. 2011 Mar 10;54(5):1347-55. doi: 10.1021/jm101396q. Epub 2011 Feb 15.
• [7] Current clinical development of PI3K pathway inhibitors in glioblastoma. Neuro Oncol. 2012 July; 14(7): 819-829.