Details of the Drug Combination

General Information of Drug Combination (ID: DCVQFAN)

• Drug Combination Name: Pyrimethamine + Ibrutinib
• Indication: Diffuse large B cell lymphoma; Status: Investigative [1]
• Component Drugs:
  Pyrimethamine (DM5X7VY): Small molecular drug
  Ibrutinib (DMHZCPO): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: TMD8
  Zero Interaction Potency (ZIP) Score: 7.372
  Bliss Independence Score: 7.191
  Loewe Additivity Score: 10.19
  LHighest Single Agent (HSA) Score: 10.677

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Pyrimethamine

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Approved	[2]

Pyrimethamine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Folate receptor alpha (FOLR1)	TTVC37M	FOLR1_HUMAN	Modulator	[7]

Pyrimethamine Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[8]
Multidrug and toxin extrusion protein 1 (SLC47A1)	DTZGT0P	S47A1_HUMAN	Substrate	[9]

Pyrimethamine Interacts with 15 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Multidrug and toxin extrusion protein 1 (SLC47A1)	OTZX0U5Q	S47A1_HUMAN	Decreases Activity	[10]
Cytochrome P450 2C9 (CYP2C9)	OTGLBN29	CP2C9_HUMAN	Decreases Activity	[11]
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Decreases Activity	[12]
Suppressor of cytokine signaling 3 (SOCS3)	OTY183WJ	SOCS3_HUMAN	Decreases Expression	[13]
Protein c-Fos (FOS)	OTJBUVWS	FOS_HUMAN	Increases Expression	[14]
Beta-hexosaminidase subunit beta (HEXB)	OTROYLCR	HEXB_HUMAN	Affects Binding	[15]
Cathepsin B (CTSB)	OTP9G5QB	CATB_HUMAN	Increases Activity	[16]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Phosphorylation	[17]
HLA class I histocompatibility antigen, alpha chain G (HLA-G)	OTMLK1KN	HLAG_HUMAN	Affects Expression	[18]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[19]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[19]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[16]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[16]
Multidrug and toxin extrusion protein 2 (SLC47A2)	OTF2CNRD	S47A2_HUMAN	Decreases Activity	[10]
Proton-coupled folate transporter (SLC46A1)	OT049V7Y	PCFT_HUMAN	Decreases Activity	[20]

Indication(s) of Ibrutinib

Disease Entry	ICD 11	Status	REF
Mantle cell lymphoma	2A85.5	Approved	[3]
Small lymphocytic lymphoma	2A82.0	Approved	[4]
Waldenstrom macroglobulinemia	2A85.4	Approved	[4]
B-cell non-hodgkin lymphoma	2B33.5	Phase 3	[5]
Diffuse large B-cell lymphoma	2A81	Phase 3	[5]
Follicular lymphoma	2A80	Phase 3	[5]
Non-hodgkin lymphoma	2B33.5	Phase 3	[5]
Pancreatic cancer	2C10	Phase 3	[5]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[6]
Solid tumour/cancer	2A00-2F9Z	Phase 2	[5]

Ibrutinib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tyrosine-protein kinase BTK (ATK)	TTGM6VW	BTK_HUMAN	Inhibitor	[21]

Ibrutinib Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[22]

Ibrutinib Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[23]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[23]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[23]

Ibrutinib Interacts with 21 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Tyrosine-protein kinase BTK (BTK)	OTG3CDVK	BTK_HUMAN	Decreases Response To Substance	[24]
CASP8 and FADD-like apoptosis regulator (CFLAR)	OTX14BAS	CFLAR_HUMAN	Decreases Expression	[25]
PR domain zinc finger protein 1 (PRDM1)	OTQLSVBS	PRDM1_HUMAN	Decreases Expression	[25]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Expression	[25]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2)	OTGVC9MY	PLCG2_HUMAN	Decreases Phosphorylation	[25]
Tumor necrosis factor alpha-induced protein 3 (TNFAIP3)	OTVLI4DD	TNAP3_HUMAN	Decreases Expression	[25]
Interleukin-10 (IL10)	OTIRFRXC	IL10_HUMAN	Decreases Expression	[25]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Decreases Expression	[25]
Polycomb complex protein BMI-1 (BMI1)	OTROVLJ0	BMI1_HUMAN	Decreases Expression	[25]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Affects Localization	[25]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[25]
Baculoviral IAP repeat-containing protein 3 (BIRC3)	OT3E95KB	BIRC3_HUMAN	Decreases Expression	[25]
Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB)	OT9RDS3H	IKKB_HUMAN	Decreases Activity	[26]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[27]
Alanine aminotransferase 1 (GPT)	OTOXOA0Q	ALAT1_HUMAN	Increases Secretion	[28]
Hemoglobin subunit beta (HBB)	OT514IKQ	HBB_HUMAN	Affects Binding	[27]
TNF receptor-associated factor 2 (TRAF2)	OT1MEZZN	TRAF2_HUMAN	Decreases Response To Substance	[25]
TNF receptor-associated factor 3 (TRAF3)	OT5TQBGV	TRAF3_HUMAN	Decreases Response To Substance	[25]
CREB-binding protein (CREBBP)	OTPA4QGM	CBP_HUMAN	Decreases Response To Substance	[25]
Mitogen-activated protein kinase kinase kinase 14 (MAP3K14)	OTT3DOOL	M3K14_HUMAN	Decreases Response To Substance	[25]
Serine/threonine-protein kinase pim-1 (PIM1)	OTWEKXTU	PIM1_HUMAN	Decreases Response To Substance	[25]

References

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• [4] Ibrutinib FDA Label
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