Details of the Drug Combination

General Information of Drug Combination (ID: DCO121Y)

• Drug Combination Name: Uracil mustard + Chlorambucil
• Indication: Adult acute myeloid leukemia; Status: Investigative [1]
• Component Drugs:
  Uracil mustard (DMHL7OB): Small molecular drug
  Chlorambucil (DMRKE63): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HL-60(TB)
  Zero Interaction Potency (ZIP) Score: 2.9
  Bliss Independence Score: 9.64
  Loewe Additivity Score: 1.47
  LHighest Single Agent (HSA) Score: 7.48

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Uracil mustard

Disease Entry	ICD 11	Status	REF
Acute myeloid leukaemia	2A60	Approved	[2]
Chronic myelogenous leukaemia	2A20.0	Approved	[3]
Polycythemia vera	2A20.4	Approved	[3]
Small lymphocytic lymphoma	2A82.0	Approved	[3]

Uracil mustard Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Modulator	[6]

Uracil mustard Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
GPI-linked NAD(P)(+)--arginine ADP-ribosyltransferase 1 (ART1)	OT7FBG5W	NAR1_HUMAN	Increases ADR	[7]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases ADR	[7]
Granulocyte-macrophage colony-stimulating factor (CSF2)	OT1M7D28	CSF2_HUMAN	Increases ADR	[7]
Poly polymerase 1 (PARP1)	OTIESHK4	PARP1_ARATH	Increases ADR	[7]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases ADR	[7]

Indication(s) of Chlorambucil

Disease Entry	ICD 11	Status	REF
Chronic lymphocytic leukaemia	2A82.0	Approved	[4]
Small lymphocytic lymphoma	2A82.0	Approved	[5]
Classic Hodgkin lymphoma	N.A.	Investigative	[5]
Follicular lymphoma	2A80	Investigative	[5]

Chlorambucil Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
DNA replication (DNA repli)	TTABD5E	NOUNIPROTAC	Intercalator	[8]

Chlorambucil Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[9]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[10]

Chlorambucil Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Glutathione S-transferase pi (GSTP1)	DEK6079	GSTP1_HUMAN	Metabolism	[11]

Chlorambucil Interacts with 37 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Decreases Response To Substance	[12]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[13]
Glutathione S-transferase A1 (GSTA1)	OTA7K5XA	GSTA1_HUMAN	Decreases Activity	[14]
Aldo-keto reductase family 1 member B10 (AKR1B10)	OTOA4HTH	AK1BA_HUMAN	Decreases Expression	[15]
Leukemia inhibitory factor (LIF)	OTO46S5S	LIF_HUMAN	Increases Expression	[15]
Aldo-keto reductase family 1 member C2 (AKR1C2)	OTQ2XMO3	AK1C2_HUMAN	Decreases Expression	[15]
Bcl-2-interacting killer (BIK)	OTTH1T3D	BIK_HUMAN	Increases Expression	[15]
F-box only protein 30 (FBXO30)	OTD1P6LA	FBX30_HUMAN	Decreases Expression	[15]
Histone chaperone ASF1A (ASF1A)	OT4S44GP	ASF1A_HUMAN	Decreases Expression	[15]
Tumor necrosis factor receptor superfamily member 10A (TNFRSF10A)	OTBPCU2O	TR10A_HUMAN	Affects Expression	[16]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[17]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Affects Expression	[18]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Increases Expression	[19]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[17]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[19]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Phosphorylation	[20]
HLA class II histocompatibility antigen, DP alpha 1 chain (HLA-DPA1)	OT7OG7Y2	DPA1_HUMAN	Affects Expression	[21]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[22]
14-3-3 protein sigma (SFN)	OTLJCZ1U	1433S_HUMAN	Increases Expression	[17]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[23]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[22]
Histone H4 (H4C1)	OTB71W46	H4_HUMAN	Decreases Expression	[20]
E3 ubiquitin-protein ligase Mdm2 (MDM2)	OTOVXARF	MDM2_HUMAN	Increases Expression	[18]
DNA repair protein RAD51 homolog 1 (RAD51)	OTNVWGC1	RAD51_HUMAN	Increases Expression	[24]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[25]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[22]
kinase isozyme 4, mitochondrial (PDK4)	OTCMHMBZ	PDK4_HUMAN	Affects Expression	[26]
Bcl-2-binding component 3, isoforms 3/4 (BBC3)	OTUAXDAY	BBC3B_HUMAN	Increases Expression	[18]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Increases Response To Substance	[27]
Dihydrofolate reductase (DHFR)	OT3DVIGM	DYR_HUMAN	Decreases Response To Substance	[28]
Cytidine deaminase (CDA)	OT3HXP6N	CDD_HUMAN	Decreases Response To Substance	[29]
Fanconi anemia group G protein (FANCG)	OT7MC8TZ	FANCG_HUMAN	Increases Response To Substance	[30]
Baculoviral IAP repeat-containing protein 2 (BIRC2)	OTFXFREP	BIRC2_HUMAN	Decreases Response To Substance	[31]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Decreases Response To Substance	[12]
ATP-binding cassette sub-family C member 2 (ABCC2)	OTJSIGV5	MRP2_HUMAN	Affects Export	[32]
Glutathione S-transferase Mu 1 (GSTM1)	OTSBF2MO	GSTM1_HUMAN	Decreases Response To Substance	[33]
Fanconi anemia group C protein (FANCC)	OTTIDM3P	FANCC_HUMAN	Increases Response To Substance	[30]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Anaplastic large cell lymphoma	DCVW1T6	SR	Investigative	[1]
Childhood T acute lymphoblastic leukemia	DCQ5MS8	CCRF-CEM	Investigative	[1]
Adenocarcinoma	DCBX4CU	HCT116	Investigative	[34]

References

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• [3] Uracil mustard FDA Label
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