Details of the Drug Combination

General Information of Drug Combination (ID: DCQYTC7)

• Drug Combination Name: Imatinib + Hydroxyurea
• Indication: Glioblastoma Multiforme; Status: Phase 1 [1]
• Component Drugs:
  Imatinib (DM7RJXL): Small molecular drug
  Hydroxyurea (DMOQVU9): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Imatinib

Disease Entry	ICD 11	Status	REF
Acute lymphoblastic leukaemia	2A85	Approved	[2]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive	N.A.	Approved	[3]
Choroidal neovascularization	9B76	Approved	[3]
Chronic eosinophilic leukemia	N.A.	Approved	[3]
Chronic myelogenous leukaemia	2A20.0	Approved	[4]
Chronic myeloid leukaemia	2A20	Approved	[5]
Dermatofibrosarcoma protuberans	N.A.	Approved	[3]
Gastrointestinal stromal tumour	2B5B	Approved	[3]
Leukemia	N.A.	Approved	[3]
Malignant peripheral nerve sheath tumor	N.A.	Approved	[3]
Myeloproliferative neoplasm	2A20	Approved	[3]
Pulmonary hypertension	BB01	Approved	[3]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[6]
Intestinal cancer	2C0Z	Phase 3	[4]
Lung cancer	2C25.0	Phase 2	[4]
Idiopathic hypereosinophilic syndrome	N.A.	Investigative	[3]
Middle East Respiratory Syndrome (MERS)	1D64	Investigative	[7]
Scleroderma	4A42	Investigative	[3]
Severe acute respiratory syndrome (SARS)	1D65	Investigative	[7]
Systemic mastocytosis	2A21.0	Investigative	[8]

Imatinib Interacts with 5 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Mcl-1 messenger RNA (MCL-1 mRNA)	TTN6ORK	MCL1_HUMAN	.	[8]
Fusion protein Bcr-Abl (Bcr-Abl)	TTS7G69	BCR_HUMAN-ABL1_HUMAN	Inhibitor	[14]
Platelet-derived growth factor receptor (PDGFR)	TTI2WET	NOUNIPROTAC	Inhibitor	[14]
Tyrosine-protein kinase Kit (KIT)	TTX41N9	KIT_HUMAN	Inhibitor	[14]
HUMAN fusion protein Bcr-Abl (Bcr-Abl)	TTE63HY	BCR_HUMAN/ABL1_HUMAN	Inhibitor	[7]

Imatinib Interacts with 6 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[15]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[16]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[17]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[18]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[19]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[17]

Imatinib Interacts with 8 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[20]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[21]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[22]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[23]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[24]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[25]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[26]
Prostaglandin G/H synthase 1 (COX-1)	DE073H6	PGH1_HUMAN	Metabolism	[22]

Imatinib Interacts with 48 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	Increases Expression	[27]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[27]
Aldehyde dehydrogenase, mitochondrial (ALDH2)	OTKJ9I3N	ALDH2_HUMAN	Decreases Expression	[28]
Eukaryotic translation initiation factor 4E (EIF4E)	OTDAWNLA	IF4E_HUMAN	Decreases Expression	[28]
Fructose-bisphosphate aldolase C (ALDOC)	OTEC13I5	ALDOC_HUMAN	Decreases Expression	[28]
Pyruvate dehydrogenase E1 component subunit beta, mitochondrial (PDHB)	OT2NHE5E	ODPB_HUMAN	Decreases Expression	[28]
Eukaryotic translation initiation factor 4B (EIF4B)	OTE8TXA8	IF4B_HUMAN	Decreases Expression	[28]
Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1)	OT5BZ1J9	P85A_HUMAN	Decreases Expression	[28]
G1/S-specific cyclin-D3 (CCND3)	OTNKPQ22	CCND3_HUMAN	Decreases Expression	[28]
Hexokinase-4 (GCK)	OTR3Q0NN	HXK4_HUMAN	Decreases Expression	[28]
Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform (PPP2CA)	OT83PT85	PP2AA_HUMAN	Increases Expression	[28]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[29]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[30]
Autophagy-related protein 13 (ATG13)	OTYMHNEJ	ATG13_HUMAN	Increases Phosphorylation	[11]
Keratin, type I cytoskeletal 14 (KRT14)	OTUVZ1DW	K1C14_HUMAN	Increases Expression	[31]
Heat shock protein beta-1 (HSPB1)	OTHFZ8ED	HSPB1_HUMAN	Increases Expression	[30]
Tyrosine-protein kinase Lck (LCK)	OT883FG9	LCK_HUMAN	Decreases Phosphorylation	[32]
ATP-dependent 6-phosphofructokinase, muscle type (PFKM)	OT1QY9JM	PFKAM_HUMAN	Decreases Expression	[33]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[34]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[30]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1)	OTA675TJ	GTR1_HUMAN	Decreases Expression	[35]
Keratin, type II cytoskeletal 5 (KRT5)	OTVGI9HT	K2C5_HUMAN	Increases Expression	[31]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[36]
Transcription factor EB (TFEB)	OTJUJJQY	TFEB_HUMAN	Affects Localization	[11]
Insulin-like growth factor-binding protein 4 (IGFBP4)	OT2HZRBD	IBP4_HUMAN	Increases Expression	[30]
Interleukin-4 receptor subunit alpha (IL4R)	OTTXOTCW	IL4RA_HUMAN	Increases Expression	[30]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[32]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[32]
Catenin beta-1 (CTNNB1)	OTZ932A3	CTNB1_HUMAN	Decreases Expression	[37]
Crk-like protein (CRKL)	OTOYSD1R	CRKL_HUMAN	Decreases Phosphorylation	[38]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Phosphorylation	[11]
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Increases Expression	[30]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Decreases Expression	[37]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[39]
Nuclear receptor subfamily 0 group B member 2 (NR0B2)	OT7UVICX	NR0B2_HUMAN	Increases Expression	[40]
NGFI-A-binding protein 2 (NAB2)	OTG4BDF3	NAB2_HUMAN	Increases Expression	[30]
TRAF family member-associated NF-kappa-B activator (TANK)	OTZSGFIK	TANK_HUMAN	Increases Expression	[30]
NACHT, LRR and PYD domains-containing protein 3 (NLRP3)	OTZM6MHU	NLRP3_HUMAN	Increases Expression	[41]
Bile acid receptor (NR1H4)	OTWZLPTB	NR1H4_HUMAN	Increases Activity	[40]
Docking protein 1 (DOK1)	OTGVRLW6	DOK1_HUMAN	Decreases Phosphorylation	[42]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B)	OTUYHB84	MLP3B_HUMAN	Increases Expression	[11]
Transcription factor SOX-17 (SOX17)	OT9H4WWE	SOX17_HUMAN	Decreases Localization	[43]
V-type proton ATPase subunit H (ATP6V1H)	OTX17GQ9	VATH_HUMAN	Increases Expression	[11]
LYR motif-containing protein 9 (LYRM9)	OT1MILTK	LYRM9_HUMAN	Affects Response To Substance	[44]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Response To Substance	[45]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Response To Substance	[46]
Tyrosine-protein kinase Lyn (LYN)	OTP686K2	LYN_HUMAN	Decreases Response To Substance	[38]
Serine/threonine-protein kinase PLK1 (PLK1)	OTRZX45T	PLK1_HUMAN	Increases Response To Substance	[34]

Indication(s) of Hydroxyurea

Disease Entry	ICD 11	Status	REF
Chronic myelogenous leukaemia	2A20.0	Approved	[9]
Desmoid tumour	2F7C	Approved	[10]
Fibromatosis	N.A.	Approved	[10]
Head and neck cancer	2D42	Approved	[10]
Melanoma	2C30	Approved	[10]
Pulmonary hypertension	BB01	Approved	[10]
Sickle-cell anaemia	3A51	Approved	[10]

Hydroxyurea Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Ribonucleoside-diphosphate reductase M2 (RRM2)	TTBWDI0	RIR2_HUMAN	Modulator	[52]

Hydroxyurea Interacts with 4 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[53]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[54]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[54]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[54]

Hydroxyurea Interacts with 85 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Solute carrier organic anion transporter family member 1B1 (SLCO1B1)	OTNEN8QK	SO1B1_HUMAN	Increases Uptake	[54]
Solute carrier organic anion transporter family member 1B3 (SLCO1B3)	OTOM3BUH	SO1B3_HUMAN	Increases Uptake	[54]
Solute carrier organic anion transporter family member 1A2 (SLCO1A2)	OTO70C5O	SO1A2_HUMAN	Increases Uptake	[54]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[47]
TP53-regulated inhibitor of apoptosis 1 (TRIAP1)	OTEAUJXN	TRIA1_HUMAN	Increases Expression	[47]
Heat shock cognate 71 kDa protein (HSPA8)	OTJI2RCI	HSP7C_HUMAN	Increases Expression	[47]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A)	OTDRV63V	GA45A_HUMAN	Increases Expression	[47]
Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B)	OTE8GBUR	RIR2B_HUMAN	Increases Expression	[47]
DNA damage-binding protein 2 (DDB2)	OTO8HVVB	DDB2_HUMAN	Increases Expression	[47]
Transcription factor E2F8 (E2F8)	OTQKZGFP	E2F8_HUMAN	Increases Expression	[50]
Transmembrane protein 250 (TMEM250)	OTLJ4G5G	TM250_HUMAN	Increases Expression	[50]
E3 ubiquitin-protein ligase TRIM38 (TRIM38)	OT6SP1M9	TRI38_HUMAN	Decreases Expression	[49]
Serine/threonine-protein kinase Chk1 (CHEK1)	OTTTI622	CHK1_HUMAN	Increases Phosphorylation	[55]
Transcription factor EC (TFEC)	OTUST8MR	TFEC_HUMAN	Decreases Expression	[49]
E3 ubiquitin-protein ligase RNF113A (RNF113A)	OTR6N7HU	R113A_HUMAN	Decreases Expression	[49]
DNA repair protein RAD51 homolog 3 (RAD51C)	OTUD6SY5	RA51C_HUMAN	Increases Expression	[56]
Protein regulator of cytokinesis 1 (PRC1)	OTHD0XS0	PRC1_HUMAN	Decreases Expression	[48]
HMG box-containing protein 1 (HBP1)	OTDPGGDV	HBP1_HUMAN	Decreases Expression	[49]
Kinesin-like protein KIF20A (KIF20A)	OTXOQHE0	KI20A_HUMAN	Decreases Expression	[49]
Myelin protein zero-like protein 1 (MPZL1)	OTJSUUHR	MPZL1_HUMAN	Decreases Expression	[49]
Serine/threonine-protein kinase Chk2 (CHEK2)	OT8ZPCNS	CHK2_HUMAN	Increases Phosphorylation	[55]
Cystatin-A (CSTA)	OT1K68KE	CYTA_HUMAN	Affects Expression	[56]
Endothelin-3 (EDN3)	OTN7Q9BE	EDN3_HUMAN	Decreases Expression	[57]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[58]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Decreases Expression	[59]
Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2)	OTIN6G20	CPT2_HUMAN	Decreases Expression	[49]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[60]
G1/S-specific cyclin-D2 (CCND2)	OTDULQF9	CCND2_HUMAN	Increases Expression	[61]
G1/S-specific cyclin-D3 (CCND3)	OTNKPQ22	CCND3_HUMAN	Increases Expression	[61]
Sodium-dependent serotonin transporter (SLC6A4)	OT6FGDLW	SC6A4_HUMAN	Decreases Expression	[59]
Cyclin-dependent kinases regulatory subunit 2 (CKS2)	OTPTMHIV	CKS2_HUMAN	Decreases Expression	[48]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[60]
Cyclin-dependent kinase inhibitor 2A (CDKN2A)	OTN0ZWAE	CDN2A_HUMAN	Increases Expression	[62]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Increases Expression	[62]
Neurogenic locus notch homolog protein 1 (NOTCH1)	OTI1WADQ	NOTC1_HUMAN	Decreases Expression	[63]
LIM/homeobox protein Lhx2 (LHX2)	OTK61NP8	LHX2_HUMAN	Decreases Expression	[49]
Max-interacting protein 1 (MXI1)	OTUQ9E0D	MXI1_HUMAN	Decreases Expression	[50]
Cyclin-G1 (CCNG1)	OT17IA9L	CCNG1_HUMAN	Increases Expression	[60]
Importin subunit alpha-1 (KPNA2)	OTU7FOE6	IMA1_HUMAN	Decreases Expression	[48]
DNA mismatch repair protein Msh6 (MSH6)	OT46FP09	MSH6_HUMAN	Decreases Expression	[49]
Serine/threonine-protein kinase PLK1 (PLK1)	OTRZX45T	PLK1_HUMAN	Decreases Phosphorylation	[63]
RecQ-like DNA helicase BLM (BLM)	OTEJOAJX	BLM_HUMAN	Decreases Expression	[49]
Ataxin-1 (ATXN1)	OTQF0HNR	ATX1_HUMAN	Decreases Expression	[49]
Ras-related protein Rap-2b (RAP2B)	OTD2NDQP	RAP2B_HUMAN	Decreases Expression	[49]
Protein BTG2 (BTG2)	OTZF6K1H	BTG2_HUMAN	Increases Expression	[49]
Transcription factor E2F1 (E2F1)	OTLKYBBC	E2F1_HUMAN	Decreases Expression	[49]
Histone-lysine N-methyltransferase MECOM (MECOM)	OTP983W8	MECOM_HUMAN	Increases Expression	[64]
Unconventional myosin-Ie (MYO1E)	OTM9YSIZ	MYO1E_HUMAN	Decreases Expression	[50]
E3 ubiquitin-protein ligase TRIM32 (TRIM32)	OTJOV0PG	TRI32_HUMAN	Decreases Expression	[49]
Serine-protein kinase ATM (ATM)	OTQVOHLT	ATM_HUMAN	Increases Phosphorylation	[63]
Oligodendrocyte transcription factor 2 (OLIG2)	OTMCN6D3	OLIG2_HUMAN	Decreases Expression	[59]
Protein BTG3 (BTG3)	OT9ANHVT	BTG3_HUMAN	Decreases Expression	[49]
Histone RNA hairpin-binding protein (SLBP)	OTVYYQRT	SLBP_HUMAN	Decreases Expression	[49]
Cyclin-dependent kinase 5 activator 1 (CDK5R1)	OTJELWK0	CD5R1_HUMAN	Increases Expression	[50]
Neutral amino acid transporter B(0) (SLC1A5)	OTE2H26Q	AAAT_HUMAN	Decreases Expression	[49]
Flap endonuclease GEN homolog 1 (GEN1)	OT1XFQXF	GEN_HUMAN	Increases Expression	[65]
Proline/serine-rich coiled-coil protein 1 (PSRC1)	OT7MDJMN	PSRC1_HUMAN	Decreases Expression	[48]
Protein aurora borealis (BORA)	OTV2ZPKP	BORA_HUMAN	Decreases Expression	[48]
Leucine-rich repeat-containing protein 47 (LRRC47)	OTSE8NAO	LRC47_HUMAN	Decreases Expression	[49]
Lipase member H (LIPH)	OTRGYLKL	LIPH_HUMAN	Decreases Expression	[50]
Cytochrome c oxidase assembly factor 7 (COA7)	OTRQJYL6	COA7_HUMAN	Decreases Expression	[49]
Mitochondrial potassium channel (CCDC51)	OTOJNHNA	MITOK_HUMAN	Decreases Expression	[49]
Integrator complex subunit 15 (INTS15)	OT3O4INM	INT15_HUMAN	Decreases Expression	[49]
Small integral membrane protein 14 (SMIM14)	OT47IF19	SIM14_HUMAN	Decreases Expression	[50]
Protein pelota homolog (PELO)	OTF3WLIM	PELO_HUMAN	Decreases Expression	[49]
TIMELESS-interacting protein (TIPIN)	OT9PZHXV	TIPIN_HUMAN	Decreases Expression	[49]
tRNA pseudouridine(38/39) synthase (PUS3)	OT6WG6M2	PUS3_HUMAN	Decreases Expression	[49]
Transmembrane protein 185B (TMEM185B)	OTGNYS0J	T185B_HUMAN	Decreases Expression	[49]
Interferon-stimulated 20 kDa exonuclease-like 2 (ISG20L2)	OT3Q11WQ	I20L2_HUMAN	Decreases Expression	[49]
GrpE protein homolog 1, mitochondrial (GRPEL1)	OT8O00YJ	GRPE1_HUMAN	Decreases Expression	[49]
Protein CLN8 (CLN8)	OT0D4CB5	CLN8_HUMAN	Decreases Expression	[49]
Inactive cell surface hyaluronidase CEMIP2 (CEMIP2)	OT9I1XUO	CEIP2_HUMAN	Decreases Expression	[50]
rRNA methyltransferase 2, mitochondrial (MRM2)	OTRYA1HU	MRM2_HUMAN	Decreases Expression	[49]
ERBB receptor feedback inhibitor 1 (ERRFI1)	OT7VZ2IZ	ERRFI_HUMAN	Decreases Expression	[50]
Frizzled-1 (FZD1)	OTZATHVS	FZD1_HUMAN	Decreases Expression	[49]
RING finger protein 24 (RNF24)	OTUZI597	RNF24_HUMAN	Decreases Expression	[50]
DNA polymerase eta (POLH)	OTN07WXU	POLH_HUMAN	Increases Expression	[66]
5'-AMP-activated protein kinase subunit beta-1 (PRKAB1)	OT1OG4QZ	AAKB1_HUMAN	Increases Expression	[49]
V-type proton ATPase 116 kDa subunit a 2 (ATP6V0A2)	OTJBDX0Y	VPP2_HUMAN	Decreases Expression	[59]
Pleckstrin homology-like domain family A member 3 (PHLDA3)	OTXFUDO2	PHLA3_HUMAN	Increases Expression	[49]
Sestrin-1 (SESN1)	OTSFDZWL	SESN1_HUMAN	Increases Expression	[49]
Solute carrier family 22 member 4 (SLC22A4)	OT4LOVI9	S22A4_HUMAN	Increases Uptake	[54]
Organic cation/carnitine transporter 2 (SLC22A5)	OTC36TYB	S22A5_HUMAN	Increases Uptake	[54]
Protein artemis (DCLRE1C)	OTW3KB1I	DCR1C_HUMAN	Increases Response To Substance	[51]
Urea transporter 2 (SLC14A2)	OTYI6SX1	UT2_HUMAN	Increases Uptake	[54]

References

• [1] ClinicalTrials.gov (NCT00154375) Study of Imatinib Mesylate in Combination With Hydroxyurea Versus Hydroxyurea Alone as an Oral Therapy in Patients With Temozolomide Resistant Progressive Glioblastoma
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] Imatinib 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: 5687).
• [5] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 078340.
• [6] ClinicalTrials.gov (NCT04356495) Treatments to Decrease the Risk of Hospitalization or Death in Elderly Outpatients With Symptomatic SARS-CoV-2 Infection (COVID-19). U.S. National Institutes of Health.
• [7] Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
• [8] Design and development of antisense drugs. Expert Opin. Drug Discov. 2008 3(10):1189-1207.
• [9] 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: 6822).
• [10] Hydroxyurea FDA Label
• [11] Imatinib disturbs lysosomal function and morphology and impairs the activity of mTORC1 in human hepatocyte cell lines. Food Chem Toxicol. 2022 Apr;162:112869. doi: 10.1016/j.fct.2022.112869. Epub 2022 Feb 16.
• [12] Insulin-like growth factor I receptor pathway inhibition by ADW742, alone or in combination with imatinib, doxorubicin, or vincristine, is a novel therapeutic approach in Ewing tumor. Clin Cancer Res. 2006 Jun 1;12(11 Pt 1):3532-40. doi: 10.1158/1078-0432.CCR-05-1778.
• [13] Sensitivity to imatinib therapy may be predicted by testing Wilms tumor gene expression and colony growth after a short in vitro incubation. Cancer. 2004 Sep 1;101(5):979-88. doi: 10.1002/cncr.20457.
• [14] A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
• [15] Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
• [16] Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2.
• [17] Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
• [18] Pharmacologic markers and predictors of responses to imatinib therapy in patients with chronic myeloid leukemia. Leuk Lymphoma. 2008 Apr;49(4):639-42.
• [19] Environmental and genetic factors affecting transport of imatinib by OATP1A2. Clin Pharmacol Ther. 2011 Jun;89(6):816-20.
• [20] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [21] The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats. Biomed Res Int. 2013;2013:789184.
• [22] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [23] Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94.
• [24] Drug Interactions Flockhart Table
• [25] Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
• [26] Drug-drug interactions with imatinib: an observational study. Medicine (Baltimore). 2016 Oct;95(40):e5076.
• [27] Chronic imatinib mesylate exposure leads to reduced intracellular drug accumulation by induction of the ABCG2 (BCRP) and ABCB1 (MDR1) drug transport pumps. Cancer Biol Ther. 2005 Jul;4(7):747-52.
• [28] A systems biology understanding of the synergistic effects of arsenic sulfide and Imatinib in BCR/ABL-associated leukemia. Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3378-83.
• [29] Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci. 2010 Dec; 118(2):485-500.
• [30] Effects of Imatinib Mesylate (Gleevec) on human islet NF-kappaB activation and chemokine production in vitro. PLoS One. 2011;6(9):e24831. doi: 10.1371/journal.pone.0024831. Epub 2011 Sep 14.
• [31] Oral lichenoid eruption secondary to imatinib (Glivec). J Dermatolog Treat. 2004 Jul;15(4):253-5. doi: 10.1080/09546630410015556.
• [32] Imatinib mesylate inhibits T-cell proliferation in vitro and delayed-type hypersensitivity in vivo. Blood. 2004 Aug 15;104(4):1094-9. doi: 10.1182/blood-2003-12-4266. Epub 2004 Apr 20.
• [33] Combination of imatinib and clotrimazole enhances cell growth inhibition in T47D breast cancer cells. Chem Biol Interact. 2015 May 25;233:147-56. doi: 10.1016/j.cbi.2015.03.028. Epub 2015 Apr 8.
• [34] Efficacy of the polo-like kinase inhibitor rigosertib, alone or in combination with Abelson tyrosine kinase inhibitors, against break point cluster region-c-Abelson-positive leukemia cells. Oncotarget. 2015 Aug 21;6(24):20231-40. doi: 10.18632/oncotarget.4047.
• [35] AMP-activated protein kinase activation primes cytoplasmic translocation and autophagic degradation of the BCR-ABL protein in CML cells. Cancer Sci. 2021 Jan;112(1):194-204. doi: 10.1111/cas.14698. Epub 2020 Nov 16.
• [36] Proapoptotic activity of bortezomib in gastrointestinal stromal tumor cells. Cancer Res. 2010 Jan 1;70(1):150-9. doi: 10.1158/0008-5472.CAN-09-1449. Epub 2009 Dec 22.
• [37] Anthelmintic Niclosamide Disrupts the Interplay of p65 and FOXM1/-catenin and Eradicates Leukemia Stem Cells in Chronic Myelogenous Leukemia. Clin Cancer Res. 2017 Feb 1;23(3):789-803. doi: 10.1158/1078-0432.CCR-16-0226. Epub 2016 Aug 4.
• [38] Establishment and characterization of a novel imatinib-sensitive chronic myeloid leukemia cell line MYL, and an imatinib-resistant subline MYL-R showing overexpression of Lyn. Eur J Haematol. 2007 May;78(5):417-31. doi: 10.1111/j.1600-0609.2007.00835.x.
• [39] The catalytic DNA topoisomerase II inhibitor dexrazoxane (ICRF-187) induces differentiation and apoptosis in human leukemia K562 cells. Mol Pharmacol. 2001 Mar;59(3):453-61. doi: 10.1124/mol.59.3.453.
• [40] Investigation of imatinib and other approved drugs as starting points for antidiabetic drug discovery with FXR modulating activity. Biochem Pharmacol. 2012 Jun 15;83(12):1674-81. doi: 10.1016/j.bcp.2012.02.027. Epub 2012 Mar 7.
• [41] Imatinib-induced hepatotoxicity via oxidative stress and activation of NLRP3 inflammasome: an in vitro and in vivo study. Arch Toxicol. 2022 Apr;96(4):1075-1087. doi: 10.1007/s00204-022-03245-x. Epub 2022 Feb 22.
• [42] Sorafenib induces apoptosis specifically in cells expressing BCR/ABL by inhibiting its kinase activity to activate the intrinsic mitochondrial pathway. Cancer Res. 2009 May 1;69(9):3927-36. doi: 10.1158/0008-5472.CAN-08-2978. Epub 2009 Apr 14.
• [43] A high-throughput screen for teratogens using human pluripotent stem cells. Toxicol Sci. 2014 Jan;137(1):76-90. doi: 10.1093/toxsci/kft239. Epub 2013 Oct 23.
• [44] Identification of Genes That Modulate Susceptibility to Formaldehyde and Imatinib by Functional Genomic Screening in Human Haploid KBM7 Cells. Toxicol Sci. 2016 May;151(1):10-22. doi: 10.1093/toxsci/kfw032. Epub 2016 Mar 22.
• [45] Disruption of the inhibitor of apoptosis protein survivin sensitizes Bcr-abl-positive cells to STI571-induced apoptosis. Cancer Res. 2005 Sep 15;65(18):8224-32. doi: 10.1158/0008-5472.CAN-05-0303.
• [46] Epigenetic down-regulation of BIM expression is associated with reduced optimal responses to imatinib treatment in chronic myeloid leukaemia. Eur J Cancer. 2009 Jul;45(10):1877-89. doi: 10.1016/j.ejca.2009.04.005. Epub 2009 May 4.
• [47] Differential expression of TP53 associated genes in Fanconi anemia cells after mitomycin C and hydroxyurea treatment. Mutat Res. 2008 Oct 30;656(1-2):1-7.
• [48] Characterization of DNA reactive and non-DNA reactive anticancer drugs by gene expression profiling. Mutat Res. 2007 Jun 1;619(1-2):16-29. doi: 10.1016/j.mrfmmm.2006.12.007. Epub 2007 Feb 8.
• [49] Utilization of CDKN1A/p21 gene for class discrimination of DNA damage-induced clastogenicity. Toxicology. 2014 Jan 6;315:8-16. doi: 10.1016/j.tox.2013.10.009. Epub 2013 Nov 6.
• [50] Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells. Arch Toxicol. 2021 May;95(5):1631-1645. doi: 10.1007/s00204-021-03014-2. Epub 2021 Mar 26.
• [51] Differences in sensitivity to DNA-damaging Agents between XRCC4- and Artemis-deficient human cells. J Radiat Res. 2011;52(4):415-24. doi: 10.1269/jrr.10168.
• [52] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [53] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [54] Transcellular movement of hydroxyurea is mediated by specific solute carrier transporters. Exp Hematol. 2011 Apr;39(4):446-56.
• [55] Oncogenic Potential of Bisphenol A and Common Environmental Contaminants in Human Mammary Epithelial Cells. Int J Mol Sci. 2020 May 25;21(10):3735. doi: 10.3390/ijms21103735.
• [56] Quantitative analysis of gene expression changes in response to genotoxic compounds. Toxicol In Vitro. 2017 Mar;39:15-28. doi: 10.1016/j.tiv.2016.11.004. Epub 2016 Nov 5.
• [57] Circulating endothelin-3 levels in patients with sickle cell disease during hydroxyurea treatment. Haematologica. 2004 Mar;89(3):360-1.
• [58] Distinct mechanisms of cell-kill by triapine and its terminally dimethylated derivative Dp44mT due to a loss or gain of activity of their copper(II) complexes. Biochem Pharmacol. 2014 Oct 1;91(3):312-22. doi: 10.1016/j.bcp.2014.08.006. Epub 2014 Aug 15.
• [59] Establishment of a 13 genes-based molecular prediction score model to discriminate the neurotoxic potential of food relevant-chemicals. Toxicol Lett. 2022 Feb 1;355:1-18. doi: 10.1016/j.toxlet.2021.10.013. Epub 2021 Nov 5.
• [60] Hydroxyurea (HU)-induced apoptosis in the mouse fetal lung. Exp Mol Pathol. 2005 Aug;79(1):59-67. doi: 10.1016/j.yexmp.2005.02.007. Epub 2005 Apr 22.
• [61] The potential of iron chelators of the pyridoxal isonicotinoyl hydrazone class as effective antiproliferative agents, IV: The mechanisms involved in inhibiting cell-cycle progression. Blood. 2001 Aug 1;98(3):842-50. doi: 10.1182/blood.v98.3.842.
• [62] Hydroxyurea induces a senescence-like change of K562 human erythroleukemia cell. J Cancer Res Clin Oncol. 2000 Aug;126(8):455-60.
• [63] PLK1 targets NOTCH1 during DNA damage and mitotic progression. J Biol Chem. 2019 Nov 22;294(47):17941-17950. doi: 10.1074/jbc.RA119.009881. Epub 2019 Oct 9.
• [64] t(3;21)(q26;q22) in myeloid leukemia: an aggressive syndrome of blast transformation associated with hydroxyurea or antimetabolite therapy. Cancer. 2006 Apr 15;106(8):1730-8. doi: 10.1002/cncr.21797.
• [65] Expression and localization of GEN1 in mouse mammary epithelial cells. J Biochem Mol Toxicol. 2014 Oct;28(10):450-5. doi: 10.1002/jbt.21584. Epub 2014 Jun 30.
• [66] Translesion polymerase is upregulated by cancer therapeutics and confers anticancer drug resistance. Cancer Res. 2014 Oct 1;74(19):5585-96. doi: 10.1158/0008-5472.CAN-14-0953. Epub 2014 Aug 14.