Details of the Drug Combination

General Information of Drug Combination (ID: DCRF4SL)

• Drug Combination Name: Cladribine + Busulfan
• Indication: High Risk Acute Myeloid Leukemia; Status: Phase 3 [1]
• Component Drugs:
  Cladribine (DM3JDRP): Small molecular drug
  Busulfan (DMXYJ9C): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Cladribine

Disease Entry	ICD 11	Status	REF
Hairy cell leukaemia	2A82.2	Approved	[2]
Multiple sclerosis	8A40	Phase 3	[3]
Relapsing-remitting multiple sclerosis	8A40.0	Phase 3	[4]

Cladribine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adenosine deaminase (ADA)	TTLP57V	ADA_HUMAN	Inhibitor	[7]

Cladribine Interacts with 4 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[8]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[9]
Multidrug resistance-associated protein 4 (ABCC4)	DTCSGPB	MRP4_HUMAN	Substrate	[9]
Equilibrative nucleoside transporter 3 (SLC29A3)	DTZAWTH	S29A3_HUMAN	Substrate	[10]

Cladribine Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Deoxycytidine kinase (DCK)	DE9FGNK	DCK_HUMAN	Metabolism	[11]

Cladribine Interacts with 17 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Expression	[12]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Affects Activity	[13]
Interleukin-4 (IL4)	OTOXBWAU	IL4_HUMAN	Increases Expression	[14]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[15]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[12]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[15]
Lamin-B1 (LMNB1)	OT100T3P	LMNB1_HUMAN	Increases Cleavage	[15]
DNA cytosine-5)-methyltransferase 1 (DNMT1)	OTM2DGTK	DNMT1_HUMAN	Decreases Expression	[16]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[16]
Signal transducer and activator of transcription 3 (STAT3)	OTAAGKYZ	STAT3_HUMAN	Increases Phosphorylation	[17]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[18]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[19]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[18]
Caspase-6 (CASP6)	OTXLD3EC	CASP6_HUMAN	Increases Activity	[18]
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN)	OTOWDUNT	PTEN_HUMAN	Increases Expression	[16]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[18]
Histone-lysine N-methyltransferase 2A (KMT2A)	OT9GLJI6	KMT2A_HUMAN	Increases Response To Substance	[20]

Indication(s) of Busulfan

Disease Entry	ICD 11	Status	REF
Chronic myelogenous leukaemia	2A20.0	Approved	[5]
Hematologic disease	3C0Z	Approved	[5]
Immunodeficiency	4A00-4A85	Approved	[5]
Leukemia	N.A.	Approved	[5]
Myeloproliferative syndrome	2A22	Approved	[6]
Systemic lupus erythematosus	4A40.0	Approved	[5]
Systemic sclerosis	4A42	Approved	[5]
Neuroblastoma	2D11.2	Investigative	[5]
Retinoblastoma	2D02.2	Investigative	[5]

Busulfan Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Modulator	[22]

Busulfan Interacts with 6 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[23]
Glutathione S-transferase alpha-1 (GSTA1)	DE4ZHS1	GSTA1_HUMAN	Metabolism	[24]
Glutathione S-transferase alpha-2 (GSTA2)	DEH49YS	GSTA2_HUMAN	Metabolism	[25]
Glutathione S-transferase pi (GSTP1)	DEK6079	GSTP1_HUMAN	Metabolism	[26]
Microsomal glutathione S-transferase 2 (MGST2)	DE31KMQ	MGST2_HUMAN	Metabolism	[27]
Glutathione S-transferase mu-1 (GSTM1)	DEYZEJA	GSTM1_HUMAN	Metabolism	[26]

Busulfan Interacts with 34 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Affects Abundance	[28]
Glutathione S-transferase Mu 1 (GSTM1)	OTSBF2MO	GSTM1_HUMAN	Affects Abundance	[28]
Microsomal glutathione S-transferase 2 (MGST2)	OT4UGTDO	MGST2_HUMAN	Decreases Response To Substance	[27]
Glutathione S-transferase A1 (GSTA1)	OTA7K5XA	GSTA1_HUMAN	Decreases Response To Substance	[29]
Serotransferrin (TF)	OT41PEMS	TRFE_HUMAN	Increases Expression	[30]
Inhibin beta A chain (INHBA)	OTSP64PQ	INHBA_HUMAN	Increases Expression	[30]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Increases Expression	[30]
Antithrombin-III (SERPINC1)	OTDFATG0	ANT3_HUMAN	Affects Expression	[31]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Increases Expression	[32]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Expression	[32]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[21]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Activity	[33]
Plasminogen activator inhibitor 1 (SERPINE1)	OTT0MPQ3	PAI1_HUMAN	Increases Expression	[32]
Thrombospondin-1 (THBS1)	OT0ECWK3	TSP1_HUMAN	Increases Expression	[32]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[34]
Tissue factor pathway inhibitor (TFPI)	OTA0FX16	TFPI1_HUMAN	Decreases Expression	[32]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Phosphorylation	[34]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4)	OTRFV19J	ATF4_HUMAN	Increases Expression	[21]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Increases Expression	[21]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Activity	[35]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Activity	[35]
Aryl hydrocarbon receptor (AHR)	OTFE4EYE	AHR_HUMAN	Increases Expression	[21]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Affects Expression	[21]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[35]
Signal transducer and activator of transcription 1-alpha/beta (STAT1)	OTLMBUZ6	STAT1_HUMAN	Affects Expression	[21]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[36]
Signal transducer and activator of transcription 2 (STAT2)	OTO9G2RZ	STAT2_HUMAN	Decreases Expression	[21]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[34]
Metal regulatory transcription factor 1 (MTF1)	OTJWVLLF	MTF1_HUMAN	Decreases Expression	[21]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Increases Expression	[21]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Expression	[21]
Pseudouridylate synthase 7 homolog (PUS7)	OTE5AQHJ	PUS7_HUMAN	Increases Expression	[37]
DNA repair nuclease/redox regulator APEX1 (APEX1)	OT53OI14	APEX1_HUMAN	Increases Response To Substance	[38]
Rho GDP-dissociation inhibitor 1 (ARHGDIA)	OTEXWJDO	GDIR1_HUMAN	Affects Response To Substance	[36]

References

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