Details of the Drug Combination

General Information of Drug Combination (ID: DCYHCN2)

• Drug Combination Name: Nilotinib + Cyclophosphamide
• Indication: Cutaneous melanoma; Status: Investigative [1]
• Component Drugs:
  Nilotinib (DM7HXWT): Small molecular drug
  Cyclophosphamide (DM4O2Z7): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: SK-MEL-5
  Zero Interaction Potency (ZIP) Score: 0.1
  Bliss Independence Score: 2.93
  Loewe Additivity Score: 1.22
  LHighest Single Agent (HSA) Score: 0.57

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Nilotinib

Disease Entry	ICD 11	Status	REF
Chronic myelogenous leukaemia	2A20.0	Approved	[2]

Nilotinib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Fusion protein Bcr-Abl (Bcr-Abl)	TTS7G69	BCR_HUMAN-ABL1_HUMAN	Modulator	[8]

Nilotinib Interacts with 5 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[9]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[10]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[9]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[11]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[11]

Nilotinib Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[12]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[13]

Nilotinib Interacts with 21 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Affects Response To Substance	[14]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Affects Response To Substance	[15]
Acetyl-CoA carboxylase 1 (ACACA)	OT5CQPZY	ACACA_HUMAN	Increases Phosphorylation	[16]
Protein c-Fos (FOS)	OTJBUVWS	FOS_HUMAN	Increases Expression	[7]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Expression	[7]
Homeobox protein Hox-B7 (HOXB7)	OTC7WYU8	HXB7_HUMAN	Increases Expression	[6]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[17]
Transcription factor JunB (JUNB)	OTG2JXV5	JUNB_HUMAN	Increases Expression	[7]
Homeobox protein Hox-B9 (HOXB9)	OTMVHQOU	HXB9_HUMAN	Increases Expression	[6]
Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6)	OTAFHAVI	ATF6A_HUMAN	Decreases Expression	[7]
Paired box protein Pax-3 (PAX3)	OTN5PJZV	PAX3_HUMAN	Decreases Expression	[6]
Paired box protein Pax-6 (PAX6)	OTOC9876	PAX6_HUMAN	Increases Expression	[6]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Increases Expression	[7]
Crk-like protein (CRKL)	OTOYSD1R	CRKL_HUMAN	Decreases Phosphorylation	[7]
Homeobox protein MOX-1 (MEOX1)	OTJEMT2D	MEOX1_HUMAN	Decreases Expression	[6]
Mesoderm posterior protein 2 (MESP2)	OT7H4LYA	MESP2_HUMAN	Decreases Expression	[6]
Transcription factor 15 (TCF15)	OTA6UCWC	TCF15_HUMAN	Decreases Expression	[6]
Oligodendrocyte transcription factor 3 (OLIG3)	OTU8XLAF	OLIG3_HUMAN	Increases Expression	[6]
ER degradation-enhancing alpha-mannosidase-like protein 1 (EDEM1)	OTWHN69S	EDEM1_HUMAN	Increases Expression	[7]
Eyes absent homolog 1 (EYA1)	OTHU807A	EYA1_HUMAN	Decreases Expression	[6]
Neurogenin-2 (NEUROG2)	OTAEMIGT	NGN2_HUMAN	Increases Expression	[6]

Indication(s) of Cyclophosphamide

Disease Entry	ICD 11	Status	REF
Advanced cancer	2A00-2F9Z	Approved	[3]
Central nervous system neoplasm	N.A.	Approved	[3]
Glioblastoma	2A00	Approved	[3]
Immunodeficiency	4A00-4A85	Approved	[3]
Inflammatory breast cancer	2C62	Approved	[3]
Lupus nephritis	4A40.0Y	Approved	[3]
Lymphoma	2A80-2A86	Approved	[3]
Multiple sclerosis	8A40	Approved	[3]
Mycosis fungoides	2B01	Approved	[3]
Plasma cell myeloma	2A83.1	Approved	[3]
Solid tumour/cancer	2A00-2F9Z	Approved	[4]
Classic Hodgkin lymphoma	N.A.	Investigative	[3]
Neuroblastoma	2D11.2	Investigative	[3]
Retinoblastoma	2D02.2	Investigative	[3]
Scleroderma	4A42	Investigative	[3]

Cyclophosphamide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Modulator	[24]

Cyclophosphamide Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 4 (ABCC4)	DTCSGPB	MRP4_HUMAN	Substrate	[25]

Cyclophosphamide Interacts with 8 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[26]
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Metabolism	[27]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[28]
Cytochrome P450 2C18 (CYP2C18)	DEZMWRE	CP2CI_HUMAN	Metabolism	[27]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[29]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[30]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[31]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[32]

Cyclophosphamide Interacts with 162 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Actin, cytoplasmic 1 (ACTB)	OT1MCP2F	ACTB_HUMAN	Decreases Expression	[33]
Band 4.1-like protein 2 (EPB41L2)	OT6UABPM	E41L2_HUMAN	Decreases Expression	[34]
Receptor activity-modifying protein 1 (RAMP1)	OT7UT2XB	RAMP1_HUMAN	Increases Expression	[34]
Cystatin-F (CST7)	OTQWZUVQ	CYTF_HUMAN	Decreases Expression	[34]
Kelch repeat and BTB domain-containing protein 11 (KBTBD11)	OTBOY3WH	KBTBB_HUMAN	Decreases Expression	[34]
Aldehyde dehydrogenase, mitochondrial (ALDH2)	OTKJ9I3N	ALDH2_HUMAN	Increases Expression	[34]
Tyrosine-protein kinase Fyn (FYN)	OTLSLVZS	FYN_HUMAN	Increases Expression	[34]
SPARC (SPARC)	OTPN90H0	SPRC_HUMAN	Increases Expression	[34]
Non-secretory ribonuclease (RNASE2)	OT8Z4FNE	RNAS2_HUMAN	Decreases Expression	[34]
Transcriptional regulator ERG (ERG)	OTOTX9VU	ERG_HUMAN	Increases Expression	[34]
Cytochrome c oxidase subunit 7A2, mitochondrial (COX7A2)	OTVT146E	CX7A2_HUMAN	Decreases Expression	[34]
Methylated-DNA--protein-cysteine methyltransferase (MGMT)	OT40A9WH	MGMT_HUMAN	Decreases Expression	[34]
Bactericidal permeability-increasing protein (BPI)	OTNN9LJ5	BPI_HUMAN	Decreases Expression	[34]
Interferon-induced GTP-binding protein Mx2 (MX2)	OT05NF37	MX2_HUMAN	Decreases Expression	[34]
Myeloblastin (PRTN3)	OT72MHP7	PRTN3_HUMAN	Decreases Expression	[34]
Protein S100-P (S100P)	OTJCXNJG	S100P_HUMAN	Decreases Expression	[34]
Transmembrane 4 L6 family member 1 (TM4SF1)	OTY0ECQN	T4S1_HUMAN	Increases Expression	[34]
Intercellular adhesion molecule 3 (ICAM3)	OTTZ5A5D	ICAM3_HUMAN	Decreases Expression	[34]
Glycine receptor subunit beta (GLRB)	OTF37UG4	GLRB_HUMAN	Increases Expression	[34]
Ras-related protein R-Ras2 (RRAS2)	OT83NCEB	RRAS2_HUMAN	Increases Expression	[34]
Bcl-2-interacting killer (BIK)	OTTH1T3D	BIK_HUMAN	Decreases Expression	[34]
Pleckstrin homology-like domain family A member 2 (PHLDA2)	OTMV9DPP	PHLA2_HUMAN	Increases Expression	[34]
Testis-expressed protein 30 (TEX30)	OT87WEPQ	TEX30_HUMAN	Decreases Expression	[34]
Ras-related GTP-binding protein A (RRAGA)	OTKISLG4	RRAGA_HUMAN	Decreases Expression	[34]
Cilium assembly protein DZIP1 (DZIP1)	OTBVPO66	DZIP1_HUMAN	Increases Expression	[34]
RNA-binding protein with multiple splicing (RBPMS)	OT1RDKR9	RBPMS_HUMAN	Increases Expression	[34]
Membrane-spanning 4-domains subfamily A member 3 (MS4A3)	OT0CEJOO	MS4A3_HUMAN	Decreases Expression	[34]
Rho GTPase-activating protein 7 (DLC1)	OTP8LMCR	RHG07_HUMAN	Increases Expression	[34]
MyoD family inhibitor domain-containing protein (MDFIC)	OTSRYBWZ	MDFIC_HUMAN	Decreases Expression	[34]
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 (GNG12)	OTOGF42G	GBG12_HUMAN	Increases Expression	[34]
Cyclic AMP-dependent transcription factor ATF-5 (ATF5)	OT03QCLM	ATF5_HUMAN	Decreases Expression	[34]
PALM2-AKAP2 fusion protein (PALM2AKAP2)	OTI618VF	PLAK2_HUMAN	Increases Expression	[34]
Dihydropyrimidinase-related protein 4 (DPYSL4)	OT3SBS2S	DPYL4_HUMAN	Increases Expression	[19]
Integral membrane protein GPR137B (GPR137B)	OT1CINQQ	G137B_HUMAN	Increases Expression	[19]
Glutaminase kidney isoform, mitochondrial (GLS)	OTGOZG2M	GLSK_HUMAN	Increases Expression	[19]
Ubiquitin-like protein ISG15 (ISG15)	OT53QQ7N	ISG15_HUMAN	Increases Expression	[19]
Stomatin (STOM)	OTC8R6EH	STOM_HUMAN	Increases Expression	[19]
Cellular retinoic acid-binding protein 2 (CRABP2)	OTY01V9G	RABP2_HUMAN	Increases Expression	[19]
Tyrosine-protein kinase receptor UFO (AXL)	OTKA2SUX	UFO_HUMAN	Increases Expression	[19]
14-3-3 protein sigma (SFN)	OTLJCZ1U	1433S_HUMAN	Increases Expression	[19]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[19]
Tumor necrosis factor ligand superfamily member 9 (TNFSF9)	OTV9L89D	TNFL9_HUMAN	Increases Expression	[19]
Galectin-7 (LGALS7)	OTMSVI7R	LEG7_HUMAN	Increases Expression	[19]
Rho GDP-dissociation inhibitor 2 (ARHGDIB)	OT9PD6CS	GDIR2_HUMAN	Increases Expression	[19]
Epithelial membrane protein 1 (EMP1)	OTSZHUHQ	EMP1_HUMAN	Increases Expression	[19]
Epithelial membrane protein 3 (EMP3)	OTODMJ1D	EMP3_HUMAN	Increases Expression	[19]
Protein ripply3 (RIPPLY3)	OT1HK35I	DSCR6_HUMAN	Increases Expression	[19]
Pro-neuregulin-1, membrane-bound isoform (NRG1)	OTZO6F1X	NRG1_HUMAN	Increases Expression	[19]
Laminin subunit gamma-2 (LAMC2)	OTJMTM72	LAMC2_HUMAN	Increases Expression	[19]
Filamin-C (FLNC)	OT3F8J6Y	FLNC_HUMAN	Increases Expression	[19]
Immediate early response gene 5 protein (IER5)	OTJPTXMD	IER5_HUMAN	Increases Expression	[19]
Keratin, type II cytoskeletal 80 (KRT80)	OTAU54U3	K2C80_HUMAN	Increases Expression	[19]
Neuropilin and tolloid-like protein 2 (NETO2)	OT0YAMC0	NETO2_HUMAN	Increases Expression	[19]
UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 2 (B3GALNT2)	OTOF6O2B	B3GL2_HUMAN	Increases Expression	[19]
Phospholipase ABHD3 (ABHD3)	OTH8P977	ABHD3_HUMAN	Increases Expression	[19]
Tumor necrosis factor receptor superfamily member 14 (TNFRSF14)	OTB82PFO	TNR14_HUMAN	Increases Expression	[19]
Major histocompatibility complex class I-related gene protein (MR1)	OTZU3XX7	HMR1_HUMAN	Increases Expression	[19]
Tumor necrosis factor receptor superfamily member 27 (EDA2R)	OTJLAIIH	TNR27_HUMAN	Increases Expression	[19]
Stathmin-3 (STMN3)	OT20F289	STMN3_HUMAN	Increases Expression	[19]
Solute carrier family 2, facilitated glucose transporter member 6 (SLC2A6)	OTVUZCLG	GTR6_HUMAN	Increases Expression	[19]
Endothelial protein C receptor (PROCR)	OTRHED17	EPCR_HUMAN	Increases Expression	[19]
Interferon-related developmental regulator 1 (IFRD1)	OT4SQMLQ	IFRD1_HUMAN	Decreases Expression	[20]
Kinesin-like protein KIF21B (KIF21B)	OTFXFIU3	KI21B_HUMAN	Decreases Expression	[20]
Large neutral amino acids transporter small subunit 3 (SLC43A1)	OTQJQY3S	LAT3_HUMAN	Decreases Expression	[20]
Cystatin-A (CSTA)	OT1K68KE	CYTA_HUMAN	Decreases Expression	[20]
Amino acid transporter heavy chain SLC3A2 (SLC3A2)	OTBR33M9	4F2_HUMAN	Decreases Expression	[20]
Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2)	OT1LQSGX	MTDC_HUMAN	Decreases Expression	[20]
Protein EVI2A (EVI2A)	OTR8RUXQ	EVI2A_HUMAN	Decreases Expression	[20]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Decreases Expression	[20]
DnaJ homolog subfamily B member 1 (DNAJB1)	OTCOSEVH	DNJB1_HUMAN	Increases Expression	[20]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Decreases Expression	[20]
Radiation-inducible immediate-early gene IEX-1 (IER3)	OTZJI5FZ	IEX1_HUMAN	Decreases Expression	[20]
Cysteine--tRNA ligase, cytoplasmic (CARS1)	OTOUZF6O	SYCC_HUMAN	Decreases Expression	[20]
Sestrin-2 (SESN2)	OT889IXY	SESN2_HUMAN	Decreases Expression	[20]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1)	OTCO26FV	HMCS1_HUMAN	Increases Expression	[20]
Transmembrane protein 267 (TMEM267)	OTEAAVK7	TM267_HUMAN	Decreases Expression	[20]
Baculoviral IAP repeat-containing protein 3 (BIRC3)	OT3E95KB	BIRC3_HUMAN	Decreases Expression	[20]
Isopentenyl-diphosphate Delta-isomerase 1 (IDI1)	OTGM06VJ	IDI1_HUMAN	Increases Expression	[20]
Nuclear receptor coactivator 7 (NCOA7)	OT2CNBOG	NCOA7_HUMAN	Decreases Expression	[20]
Alanine aminotransferase 2 (GPT2)	OTS5VF7N	ALAT2_HUMAN	Decreases Expression	[20]
Nanos homolog 1 (NANOS1)	OT3UNZZY	NANO1_HUMAN	Increases Expression	[20]
Heat shock protein 105 kDa (HSPH1)	OTVRR73T	HS105_HUMAN	Increases Expression	[20]
Insulin gene enhancer protein ISL-2 (ISL2)	OT43PD2V	ISL2_HUMAN	Decreases Expression	[20]
E3 ubiquitin-protein ligase pellino homolog 1 (PELI1)	OTMLBCLC	PELI1_HUMAN	Decreases Expression	[20]
Centriolar and ciliogenesis-associated protein HYLS1 (HYLS1)	OT3SW5UC	HYLS1_HUMAN	Decreases Expression	[20]
Tribbles homolog 3 (TRIB3)	OTG5OS7X	TRIB3_HUMAN	Decreases Expression	[20]
Glutathione-specific gamma-glutamylcyclotransferase 1 (CHAC1)	OTJGE772	CHAC1_HUMAN	Decreases Expression	[20]
Transmembrane 6 superfamily member 1 (TM6SF1)	OTQR4I2N	TM6S1_HUMAN	Decreases Expression	[20]
Protein FAM107B (FAM107B)	OT5RG4J0	F107B_HUMAN	Decreases Expression	[20]
Lysine-rich coiled-coil protein 1 (KRCC1)	OTMMV6WZ	KRCC1_HUMAN	Decreases Expression	[20]
DnaJ homolog subfamily B member 4 (DNAJB4)	OTUD01BK	DNJB4_HUMAN	Increases Expression	[20]
SLAM family member 5 (CD84)	OTAY5B0F	SLAF5_HUMAN	Increases Expression	[20]
Nuclear factor erythroid 2-related factor 3 (NFE2L3)	OT1MGXT0	NF2L3_HUMAN	Decreases Expression	[20]
Apoptotic protease-activating factor 1 (APAF1)	OTJWIVY0	APAF_HUMAN	Decreases Expression	[21]
Growth arrest-specific protein 2 (GAS2)	OT50JKXQ	GAS2_HUMAN	Increases Expression	[35]
Slit homolog 1 protein (SLIT1)	OT35RBNT	SLIT1_HUMAN	Decreases Expression	[22]
DnaJ homolog subfamily B member 6 (DNAJB6)	OTMHIIAN	DNJB6_HUMAN	Increases Expression	[35]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Activity	[36]
Follitropin subunit beta (FSHB)	OTGLS283	FSHB_HUMAN	Increases Expression	[37]
Thymidine kinase, cytosolic (TK1)	OTY5JFM1	KITH_HUMAN	Increases Mutagenesis	[38]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[36]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[39]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[40]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Phosphorylation	[41]
Natriuretic peptides B (NPPB)	OTSN2IPY	ANFB_HUMAN	Increases Expression	[42]
Troponin I, cardiac muscle (TNNI3)	OT65E12V	TNNI3_HUMAN	Increases Expression	[42]
Tumor necrosis factor alpha-induced protein 3 (TNFAIP3)	OTVLI4DD	TNAP3_HUMAN	Increases Expression	[43]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A)	OTDRV63V	GA45A_HUMAN	Increases Expression	[21]
Endothelin receptor type B (EDNRB)	OTLLZV3P	EDNRB_HUMAN	Increases Expression	[22]
Insulin-like growth factor-binding protein 5 (IGFBP5)	OTRE5V0C	IBP5_HUMAN	Decreases Expression	[22]
Proteasome subunit alpha type-5 (PSMA5)	OT38E6Y1	PSA5_HUMAN	Increases Expression	[35]
HLA class I histocompatibility antigen, alpha chain F (HLA-F)	OT76CM19	HLAF_HUMAN	Increases Expression	[22]
Phospholipid hydroperoxide glutathione peroxidase GPX4 (GPX4)	OTRAFFX2	GPX4_HUMAN	Increases Expression	[35]
Cytosolic purine 5'-nucleotidase (NT5C2)	OTJMF66Z	5NTC_HUMAN	Increases Expression	[22]
Tumor protein D52 (TPD52)	OTPKSK43	TPD52_HUMAN	Decreases Expression	[43]
Potassium voltage-gated channel subfamily KQT member 4 (KCNQ4)	OT29B58J	KCNQ4_HUMAN	Decreases Expression	[22]
Heterogeneous nuclear ribonucleoprotein K (HNRNPK)	OTNPRM8U	HNRPK_HUMAN	Increases Expression	[35]
Protein BTG2 (BTG2)	OTZF6K1H	BTG2_HUMAN	Increases Expression	[21]
Calicin (CCIN)	OTRFZOT0	CALI_HUMAN	Increases Expression	[35]
Programmed cell death protein 4 (PDCD4)	OTZ6NXUX	PDCD4_HUMAN	Decreases Expression	[43]
Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B)	OTE8GBUR	RIR2B_HUMAN	Increases Expression	[44]
Partitioning defective 3 homolog (PARD3)	OTH5BPLO	PARD3_HUMAN	Decreases Expression	[22]
GATOR1 complex protein NPRL2 (NPRL2)	OTOB10MO	NPRL2_HUMAN	Decreases Expression	[22]
F-box/WD repeat-containing protein 7 (FBXW7)	OTJXE4OT	FBXW7_HUMAN	Increases Expression	[21]
Rho guanine nucleotide exchange factor 26 (ARHGEF26)	OTX0U8PX	ARHGQ_HUMAN	Increases Expression	[22]
Polyadenylate-binding protein-interacting protein 1 (PAIP1)	OTL2F5T5	PAIP1_HUMAN	Decreases Expression	[22]
Large subunit GTPase 1 homolog (LSG1)	OTDAXJ9L	LSG1_HUMAN	Decreases Expression	[22]
Glyoxalase domain-containing protein 4 (GLOD4)	OTBJKFXA	GLOD4_HUMAN	Decreases Expression	[22]
DNA-directed DNA/RNA polymerase mu (POLM)	OT0SRIP4	DPOLM_HUMAN	Increases Expression	[22]
Ubiquitin-like-conjugating enzyme ATG3 (ATG3)	OT28VBVK	ATG3_HUMAN	Decreases Expression	[22]
Regulator of telomere elongation helicase 1 (RTEL1)	OTI3PJCT	RTEL1_HUMAN	Increases Expression	[35]
FK506-binding protein-like (FKBPL)	OTR9ND6K	FKBPL_HUMAN	Increases Expression	[45]
Mitochondrial pyruvate carrier 2 (MPC2)	OT0GHXGG	MPC2_HUMAN	Affects Response To Substance	[23]
Krueppel-like factor 5 (KLF5)	OT1ABI9N	KLF5_HUMAN	Affects Response To Substance	[23]
D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1)	OT62RL5P	BDH_HUMAN	Affects Response To Substance	[23]
Melanoma-associated antigen D1 (MAGED1)	OT6EOLFC	MAGD1_HUMAN	Affects Response To Substance	[23]
Pro-adrenomedullin (ADM)	OT7T0TA4	ADML_HUMAN	Affects Response To Substance	[23]
Peptidyl-prolyl cis-trans isomerase FKBP1B (FKBP1B)	OT8CMPB2	FKB1B_HUMAN	Affects Response To Substance	[23]
L-lactate dehydrogenase B chain (LDHB)	OT9B1CT3	LDHB_HUMAN	Affects Response To Substance	[23]
Epsilon-sarcoglycan (SGCE)	OT9F17JB	SGCE_HUMAN	Affects Response To Substance	[23]
Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1)	OTAYZZE6	AL3A1_HUMAN	Affects Response To Substance	[46]
Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3)	OTB97VIK	IF2B3_HUMAN	Affects Response To Substance	[23]
Cochlin (COCH)	OTBEHD89	COCH_HUMAN	Affects Response To Substance	[23]
Fibronectin type III domain-containing protein 3B (FNDC3B)	OTBILGDR	FND3B_HUMAN	Affects Response To Substance	[23]
Tropomyosin alpha-1 chain (TPM1)	OTD73X6R	TPM1_HUMAN	Affects Response To Substance	[23]
Very long chain fatty acid elongase 2 (ELOVL2)	OTDAF6U3	ELOV2_HUMAN	Affects Response To Substance	[23]
Protein AF1q (MLLT11)	OTG5RVHC	AF1Q_HUMAN	Decreases Response To Substance	[47]
Troponin I, fast skeletal muscle (TNNI2)	OTGGZFSC	TNNI2_HUMAN	Increases ADR	[18]
Tomoregulin-1 (TMEFF1)	OTH6M3CH	TEFF1_HUMAN	Affects Response To Substance	[23]
DNA damage-inducible transcript 4 protein (DDIT4)	OTHY8SY4	DDIT4_HUMAN	Affects Response To Substance	[23]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Affects Response To Substance	[48]
Heat shock cognate 71 kDa protein (HSPA8)	OTJI2RCI	HSP7C_HUMAN	Affects Response To Substance	[23]
Nidogen-1 (NID1)	OTKLBLS6	NID1_HUMAN	Affects Response To Substance	[23]
Homeobox protein Hox-A1 (HOXA1)	OTMSOJ7D	HXA1_HUMAN	Affects Response To Substance	[23]
Trypsin-3 (PRSS3)	OTN3S5YB	TRY3_HUMAN	Affects Response To Substance	[23]
Melanoma-associated antigen D4 (MAGED4B)	OTO37U7W	MAGD4_HUMAN	Affects Response To Substance	[23]
Opsin-3 (OPN3)	OTON6BFU	OPN3_HUMAN	Affects Response To Substance	[23]
Heat shock-related 70 kDa protein 2 (HSPA2)	OTSDET7B	HSP72_HUMAN	Affects Response To Substance	[23]
Max-interacting protein 1 (MXI1)	OTUQ9E0D	MXI1_HUMAN	Affects Response To Substance	[23]
Glycogen debranching enzyme (AGL)	OTWBM7WY	GDE_HUMAN	Affects Response To Substance	[23]
Myosin-10 (MYH10)	OTXN2WXS	MYH10_HUMAN	Affects Response To Substance	[23]
Sal-like protein 1 (SALL1)	OTYYZGLH	SALL1_HUMAN	Affects Response To Substance	[23]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Chronic myelogenous leukemia	DCNTP5T	K-562	Investigative	[49]
Adenocarcinoma	DCT01XY	OVCAR3	Investigative	[1]
Adenocarcinoma	DCL4DHD	NCIH23	Investigative	[1]
Non-small cell lung carcinoma	DCYAB4I	HOP-92	Investigative	[1]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976
• [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: 5697).
• [3] Cyclophosphamide FDA Label
• [4] 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: 7154).
• [5] Assessment of the inhibition potential of Licochalcone A against human UDP-glucuronosyltransferases. Food Chem Toxicol. 2016 Apr;90:112-22.
• [6] Exposure-based assessment of chemical teratogenicity using morphogenetic aggregates of human embryonic stem cells. Reprod Toxicol. 2020 Jan;91:74-91. doi: 10.1016/j.reprotox.2019.10.004. Epub 2019 Nov 8.
• [7] Endoplasmic reticulum stress-mediated apoptosis in imatinib-resistant leukemic K562-r cells triggered by AMN107 combined with arsenic trioxide. Exp Biol Med (Maywood). 2013 Aug 1;238(8):932-42. doi: 10.1177/1535370213492689. Epub 2013 Jul 24.
• [8] 2007 FDA drug approvals: a year of flux. Nat Rev Drug Discov. 2008 Feb;7(2):107-9.
• [9] Interaction of nilotinib, dasatinib and bosutinib with ABCB1 and ABCG2: implications for altered anti-cancer effects and pharmacological properties. Br J Pharmacol. 2009 Oct;158(4):1153-64.
• [10] KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01665)
• [11] Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
• [12] Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib, and nilotinib. Blood. 2011 Feb 24;117(8):e75-87.
• [13] Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
• [14] Resistance to daunorubicin, imatinib, or nilotinib depends on expression levels of ABCB1 and ABCG2 in human leukemia cells. Chem Biol Interact. 2014 Aug 5;219:203-10. doi: 10.1016/j.cbi.2014.06.009. Epub 2014 Jun 19.
• [15] Reversal of ABCB1 mediated efflux by imatinib and nilotinib in cells expressing various transporter levels. Chem Biol Interact. 2017 Aug 1;273:171-179. doi: 10.1016/j.cbi.2017.06.012. Epub 2017 Jun 13.
• [16] Multi-parameter in vitro toxicity testing of crizotinib, sunitinib, erlotinib, and nilotinib in human cardiomyocytes. Toxicol Appl Pharmacol. 2013 Oct 1;272(1):245-55.
• [17] Nilotinib reduced the viability of human ovarian cancer cells via mitochondria-dependent apoptosis, independent of JNK activation. Toxicol In Vitro. 2016 Mar;31:1-11. doi: 10.1016/j.tiv.2015.11.002. Epub 2015 Nov 6.
• [18] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [19] Genomic profiling uncovers a molecular pattern for toxicological characterization of mutagens and promutagens in vitro. Toxicol Sci. 2011 Jul;122(1):185-97.
• [20] Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
• [21] Comparison of Drug Metabolism and Its Related Hepatotoxic Effects in HepaRG, Cryopreserved Human Hepatocytes, and HepG2 Cell Cultures. Biol Pharm Bull. 2018 May 1;41(5):722-732. doi: 10.1248/bpb.b17-00913. Epub 2018 Feb 14.
• [22] Effect of nephrotoxicants and hepatotoxicants on gene expression profile in human peripheral blood mononuclear cells. Biochem Biophys Res Commun. 2010 Oct 15;401(2):245-50. doi: 10.1016/j.bbrc.2010.09.039. Epub 2010 Sep 16.
• [23] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.
• [24] O6-methylguanine-DNA methyltransferase activity and sensitivity to cyclophosphamide and cisplatin in human lung tumor xenografts. Int J Cancer. 1998 Sep 11;77(6):919-22.
• [25] Interaction of oxazaphosphorines with multidrug resistance-associated protein 4 (MRP4). AAPS J. 2010 Sep;12(3):300-8.
• [26] Effects of ketoconazole on cyclophosphamide metabolism: evaluation of CYP3A4 inhibition effect using the in vitro and in vivo models. Exp Anim. 2018 Feb 9;67(1):71-82.
• [27] Development of a substrate-activity based approach to identify the major human liver P-450 catalysts of cyclophosphamide and ifosfamide activation based on cDNA-expressed activities and liver microsomal P-450 profiles. Drug Metab Dispos. 1999 Jun;27(6):655-66.
• [28] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [29] Enhanced cyclophosphamide and ifosfamide activation in primary human hepatocyte cultures: response to cytochrome P-450 inducers and autoinduction by oxazaphosphorines. Cancer Res. 1997 May 15;57(10):1946-54.
• [30] CYP2C9 polymorphisms in human tumors. Anticancer Res. 2006 Jan-Feb;26(1A):299-305.
• [31] The effect of cyclophosphamide with and without dexamethasone on cytochrome P450 3A4 and 2B6 in human hepatocytes. Drug Metab Dispos. 2002 Jul;30(7):814-22.
• [32] Cytochrome P450 pharmacogenetics and cancer. Oncogene. 2006 Mar 13;25(11):1679-91.
• [33] Effect of cyclophosphamide on gene expression of cytochromes p450 and beta-actin in the HL-60 cell line. Eur J Pharmacol. 2002 Aug 9;449(3):197-205.
• [34] Comparative gene expression analysis of a chronic myelogenous leukemia cell line resistant to cyclophosphamide using oligonucleotide arrays and response to tyrosine kinase inhibitors. Leuk Res. 2007 Nov;31(11):1511-20.
• [35] Chronic cyclophosphamide exposure alters the profile of rat sperm nuclear matrix proteins. Biol Reprod. 2007 Aug;77(2):303-11. doi: 10.1095/biolreprod.107.060244. Epub 2007 May 2.
• [36] PXR-mediated induction of P-glycoprotein by anticancer drugs in a human colon adenocarcinoma-derived cell line. Cancer Chemother Pharmacol. 2010 Sep;66(4):765-71. doi: 10.1007/s00280-009-1221-4. Epub 2009 Dec 30.
• [37] Suppression of spermatogenesis in patients with Beh?et's disease treated with cyclophosphamide and colchicine. Fertil Steril. 1981 Jul;36(1):76-80. doi: 10.1016/s0015-0282(16)45622-0.
• [38] Development of an integrated assay in human TK6 cells to permit comprehensive genotoxicity analysis in vitro. Mutat Res Genet Toxicol Environ Mutagen. 2020 Jan;849:503129. doi: 10.1016/j.mrgentox.2019.503129. Epub 2019 Dec 27.
• [39] Bortezomib is synergistic with rituximab and cyclophosphamide in inducing apoptosis of mantle cell lymphoma cells in vitro and in vivo. Leukemia. 2008 Jan;22(1):179-85. doi: 10.1038/sj.leu.2404959. Epub 2007 Sep 27.
• [40] Profiling the immunotoxicity of chemicals based on in vitro evaluation by a combination of the Multi-ImmunoTox assay and the IL-8 Luc assay. Arch Toxicol. 2018 Jun;92(6):2043-2054. doi: 10.1007/s00204-018-2199-7. Epub 2018 Mar 29.
• [41] Distinct Orchestration and Dynamic Processes on -H2AX and p-H3 for Two Major Types of Genotoxic Chemicals Revealed by Mass Spectrometry Analysis. Chem Res Toxicol. 2020 Aug 17;33(8):2108-2119. doi: 10.1021/acs.chemrestox.0c00104. Epub 2020 Jun 17.
• [42] Cardiac toxicity of high-dose cyclophosphamide in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation. Int J Hematol. 2007 Jun;85(5):408-14. doi: 10.1532/IJH97.E0620.
• [43] Human embryonic stem cell derived hepatocyte-like cells as a tool for in vitro hazard assessment of chemical carcinogenicity. Toxicol Sci. 2011 Dec;124(2):278-90. doi: 10.1093/toxsci/kfr225. Epub 2011 Aug 27.
• [44] Validation of a genotoxicity test based on p53R2 gene expression in human lymphoblastoid cells. Mutat Res. 2011 Sep 18;724(1-2):76-85. doi: 10.1016/j.mrgentox.2011.06.003. Epub 2011 Jun 17.
• [45] The differential effects of cyclophosphamide, epirubicin and 5-fluorouracil on apoptotic marker (CPP-32), pro-apoptotic protein (p21(WAF-1)) and anti-apoptotic protein (bcl-2) in breast cancer cells. Breast Cancer Res Treat. 2003 Aug;80(3):239-44. doi: 10.1023/A:1024995202135.
• [46] Relations between polymorphisms in drug-metabolising enzymes and toxicity of chemotherapy with cyclophosphamide, thiotepa and carboplatin. Pharmacogenet Genomics. 2008 Nov;18(11):1009-15. doi: 10.1097/FPC.0b013e328313aaa4.
• [47] The evaluation of Cannabidiol's effect on the immunotherapy of Burkitt lymphoma. Biochem Biophys Res Commun. 2019 Nov 26;520(1):225-230. doi: 10.1016/j.bbrc.2019.10.001. Epub 2019 Oct 3.
• [48] Manganese superoxide dismutase polymorphism, treatment-related toxicity and disease-free survival in SWOG 8897 clinical trial for breast cancer. Breast Cancer Res Treat. 2010 Nov;124(2):433-9. doi: 10.1007/s10549-010-0840-0. Epub 2010 Mar 23.
• [49] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966