Details of the Drug Combination

General Information of Drug Combination (ID: DCK37TP)

• Drug Combination Name: Verapamil + Hydroxyurea
• Indication: Cancer; Status: Phase 1 [1]
• Component Drugs:
  Verapamil (DMA7PEW): Small molecular drug
  Hydroxyurea (DMOQVU9): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Verapamil

Disease Entry	ICD 11	Status	REF
Angina pectoris	BA40	Approved	[2]
Atrial fibrillation	BC81.3	Approved	[2]
Classic phenylketonuria	N.A.	Approved	[2]
Hypertension	BA00-BA04	Approved	[3]
Malignant essential hypertension	BA00	Approved	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2/3	[4]

Verapamil Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Voltage-gated calcium channel alpha Cav3.1 (CACNA1G)	TT729IR	CAC1G_HUMAN	Blocker	[7]
HUMAN two pore channel subtype 2 (TPC2)	TTHQJ2Y	TPC2_HUMAN	Blocker	[8]

Verapamil Interacts with 6 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[9]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[10]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[11]
Multidrug resistance protein 3 (ABCB4)	DTZRMK5	MDR3_HUMAN	Substrate	[12]
Organic cation/carnitine transporter 2 (SLC22A5)	DT3HUVD	S22A5_HUMAN	Substrate	[13]
Organic cation/carnitine transporter 1 (SLC22A4)	DT2EG60	S22A4_HUMAN	Substrate	[14]

Verapamil Interacts with 10 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[15]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[16]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[17]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[18]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[19]
Cytochrome P450 2C18 (CYP2C18)	DEZMWRE	CP2CI_HUMAN	Metabolism	[18]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[20]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[21]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[18]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[22]

Verapamil Interacts with 24 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[23]
Dynamin-1-like protein (DNM1L)	OTXK1Q1G	DNM1L_HUMAN	Increases Phosphorylation	[24]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Activity	[25]
Organic cation/carnitine transporter 2 (SLC22A5)	OTC36TYB	S22A5_HUMAN	Decreases Activity	[26]
ATP-binding cassette sub-family C member 6 (ABCC6)	OTZT0LKT	MRP6_HUMAN	Decreases Activity	[27]
Metalloproteinase inhibitor 1 (TIMP1)	OTOXC51H	TIMP1_HUMAN	Affects Expression	[28]
Protein c-Fos (FOS)	OTJBUVWS	FOS_HUMAN	Increases Expression	[29]
Natriuretic peptides A (NPPA)	OTMQNTNX	ANF_HUMAN	Increases Expression	[30]
Platelet basic protein (PPBP)	OT1FHGQS	CXCL7_HUMAN	Decreases Expression	[31]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Decreases Expression	[32]
Potassium voltage-gated channel subfamily A member 3 (KCNA3)	OTXSP3AA	KCNA3_HUMAN	Decreases Activity	[33]
Galanin peptides (GAL)	OTB3VPTO	GALA_HUMAN	Affects Expression	[28]
Alpha-1D adrenergic receptor (ADRA1D)	OTW2CD1O	ADA1D_HUMAN	Affects Binding	[34]
MHC class II transactivator (CIITA)	OTRJNZFO	C2TA_HUMAN	Affects Expression	[35]
Alpha-1A adrenergic receptor (ADRA1A)	OTUIWCL5	ADA1A_HUMAN	Affects Binding	[34]
Alpha-1B adrenergic receptor (ADRA1B)	OTSAYAFD	ADA1B_HUMAN	Affects Binding	[34]
Multidrug and toxin extrusion protein 1 (SLC47A1)	OTZX0U5Q	S47A1_HUMAN	Decreases Activity	[36]
Potassium voltage-gated channel subfamily D member 3 (KCND3)	OTRPIH7J	KCND3_HUMAN	Decreases Activity	[37]
Voltage-dependent L-type calcium channel subunit alpha-1C (CACNA1C)	OT6KFNMS	CAC1C_HUMAN	Increases Response To Substance	[38]
Sodium channel protein type 5 subunit alpha (SCN5A)	OTGYZWR6	SCN5A_HUMAN	Increases ADR	[39]
Calcium-activated potassium channel subunit beta-1 (KCNMB1)	OTO4KNJ4	KCMB1_HUMAN	Affects Response To Substance	[40]
Beta-1 adrenergic receptor (ADRB1)	OTQBWN4U	ADRB1_HUMAN	Affects Response To Substance	[41]
Beta-1 adrenergic receptor (ADRB1)	OTQBWN4U	ADRB1_HUMAN	Increases Response	[41]
Potassium voltage-gated channel subfamily E member 1 (KCNE1)	OTZNQUW9	KCNE1_HUMAN	Increases ADR	[39]

Indication(s) of Hydroxyurea

Disease Entry	ICD 11	Status	REF
Chronic myelogenous leukaemia	2A20.0	Approved	[5]
Desmoid tumour	2F7C	Approved	[6]
Fibromatosis	N.A.	Approved	[6]
Head and neck cancer	2D42	Approved	[6]
Melanoma	2C30	Approved	[6]
Pulmonary hypertension	BB01	Approved	[6]
Sickle-cell anaemia	3A51	Approved	[6]

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	[47]

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	[48]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[49]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[49]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[49]

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	[49]
Solute carrier organic anion transporter family member 1B3 (SLCO1B3)	OTOM3BUH	SO1B3_HUMAN	Increases Uptake	[49]
Solute carrier organic anion transporter family member 1A2 (SLCO1A2)	OTO70C5O	SO1A2_HUMAN	Increases Uptake	[49]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[42]
TP53-regulated inhibitor of apoptosis 1 (TRIAP1)	OTEAUJXN	TRIA1_HUMAN	Increases Expression	[42]
Heat shock cognate 71 kDa protein (HSPA8)	OTJI2RCI	HSP7C_HUMAN	Increases Expression	[42]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A)	OTDRV63V	GA45A_HUMAN	Increases Expression	[42]
Ribonucleoside-diphosphate reductase subunit M2 B (RRM2B)	OTE8GBUR	RIR2B_HUMAN	Increases Expression	[42]
DNA damage-binding protein 2 (DDB2)	OTO8HVVB	DDB2_HUMAN	Increases Expression	[42]
Transcription factor E2F8 (E2F8)	OTQKZGFP	E2F8_HUMAN	Increases Expression	[45]
Transmembrane protein 250 (TMEM250)	OTLJ4G5G	TM250_HUMAN	Increases Expression	[45]
E3 ubiquitin-protein ligase TRIM38 (TRIM38)	OT6SP1M9	TRI38_HUMAN	Decreases Expression	[44]
Serine/threonine-protein kinase Chk1 (CHEK1)	OTTTI622	CHK1_HUMAN	Increases Phosphorylation	[50]
Transcription factor EC (TFEC)	OTUST8MR	TFEC_HUMAN	Decreases Expression	[44]
E3 ubiquitin-protein ligase RNF113A (RNF113A)	OTR6N7HU	R113A_HUMAN	Decreases Expression	[44]
DNA repair protein RAD51 homolog 3 (RAD51C)	OTUD6SY5	RA51C_HUMAN	Increases Expression	[51]
Protein regulator of cytokinesis 1 (PRC1)	OTHD0XS0	PRC1_HUMAN	Decreases Expression	[43]
HMG box-containing protein 1 (HBP1)	OTDPGGDV	HBP1_HUMAN	Decreases Expression	[44]
Kinesin-like protein KIF20A (KIF20A)	OTXOQHE0	KI20A_HUMAN	Decreases Expression	[44]
Myelin protein zero-like protein 1 (MPZL1)	OTJSUUHR	MPZL1_HUMAN	Decreases Expression	[44]
Serine/threonine-protein kinase Chk2 (CHEK2)	OT8ZPCNS	CHK2_HUMAN	Increases Phosphorylation	[50]
Cystatin-A (CSTA)	OT1K68KE	CYTA_HUMAN	Affects Expression	[51]
Endothelin-3 (EDN3)	OTN7Q9BE	EDN3_HUMAN	Decreases Expression	[52]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[53]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Decreases Expression	[54]
Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2)	OTIN6G20	CPT2_HUMAN	Decreases Expression	[44]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[55]
G1/S-specific cyclin-D2 (CCND2)	OTDULQF9	CCND2_HUMAN	Increases Expression	[56]
G1/S-specific cyclin-D3 (CCND3)	OTNKPQ22	CCND3_HUMAN	Increases Expression	[56]
Sodium-dependent serotonin transporter (SLC6A4)	OT6FGDLW	SC6A4_HUMAN	Decreases Expression	[54]
Cyclin-dependent kinases regulatory subunit 2 (CKS2)	OTPTMHIV	CKS2_HUMAN	Decreases Expression	[43]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[55]
Cyclin-dependent kinase inhibitor 2A (CDKN2A)	OTN0ZWAE	CDN2A_HUMAN	Increases Expression	[57]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Increases Expression	[57]
Neurogenic locus notch homolog protein 1 (NOTCH1)	OTI1WADQ	NOTC1_HUMAN	Decreases Expression	[58]
LIM/homeobox protein Lhx2 (LHX2)	OTK61NP8	LHX2_HUMAN	Decreases Expression	[44]
Max-interacting protein 1 (MXI1)	OTUQ9E0D	MXI1_HUMAN	Decreases Expression	[45]
Cyclin-G1 (CCNG1)	OT17IA9L	CCNG1_HUMAN	Increases Expression	[55]
Importin subunit alpha-1 (KPNA2)	OTU7FOE6	IMA1_HUMAN	Decreases Expression	[43]
DNA mismatch repair protein Msh6 (MSH6)	OT46FP09	MSH6_HUMAN	Decreases Expression	[44]
Serine/threonine-protein kinase PLK1 (PLK1)	OTRZX45T	PLK1_HUMAN	Decreases Phosphorylation	[58]
RecQ-like DNA helicase BLM (BLM)	OTEJOAJX	BLM_HUMAN	Decreases Expression	[44]
Ataxin-1 (ATXN1)	OTQF0HNR	ATX1_HUMAN	Decreases Expression	[44]
Ras-related protein Rap-2b (RAP2B)	OTD2NDQP	RAP2B_HUMAN	Decreases Expression	[44]
Protein BTG2 (BTG2)	OTZF6K1H	BTG2_HUMAN	Increases Expression	[44]
Transcription factor E2F1 (E2F1)	OTLKYBBC	E2F1_HUMAN	Decreases Expression	[44]
Histone-lysine N-methyltransferase MECOM (MECOM)	OTP983W8	MECOM_HUMAN	Increases Expression	[59]
Unconventional myosin-Ie (MYO1E)	OTM9YSIZ	MYO1E_HUMAN	Decreases Expression	[45]
E3 ubiquitin-protein ligase TRIM32 (TRIM32)	OTJOV0PG	TRI32_HUMAN	Decreases Expression	[44]
Serine-protein kinase ATM (ATM)	OTQVOHLT	ATM_HUMAN	Increases Phosphorylation	[58]
Oligodendrocyte transcription factor 2 (OLIG2)	OTMCN6D3	OLIG2_HUMAN	Decreases Expression	[54]
Protein BTG3 (BTG3)	OT9ANHVT	BTG3_HUMAN	Decreases Expression	[44]
Histone RNA hairpin-binding protein (SLBP)	OTVYYQRT	SLBP_HUMAN	Decreases Expression	[44]
Cyclin-dependent kinase 5 activator 1 (CDK5R1)	OTJELWK0	CD5R1_HUMAN	Increases Expression	[45]
Neutral amino acid transporter B(0) (SLC1A5)	OTE2H26Q	AAAT_HUMAN	Decreases Expression	[44]
Flap endonuclease GEN homolog 1 (GEN1)	OT1XFQXF	GEN_HUMAN	Increases Expression	[60]
Proline/serine-rich coiled-coil protein 1 (PSRC1)	OT7MDJMN	PSRC1_HUMAN	Decreases Expression	[43]
Protein aurora borealis (BORA)	OTV2ZPKP	BORA_HUMAN	Decreases Expression	[43]
Leucine-rich repeat-containing protein 47 (LRRC47)	OTSE8NAO	LRC47_HUMAN	Decreases Expression	[44]
Lipase member H (LIPH)	OTRGYLKL	LIPH_HUMAN	Decreases Expression	[45]
Cytochrome c oxidase assembly factor 7 (COA7)	OTRQJYL6	COA7_HUMAN	Decreases Expression	[44]
Mitochondrial potassium channel (CCDC51)	OTOJNHNA	MITOK_HUMAN	Decreases Expression	[44]
Integrator complex subunit 15 (INTS15)	OT3O4INM	INT15_HUMAN	Decreases Expression	[44]
Small integral membrane protein 14 (SMIM14)	OT47IF19	SIM14_HUMAN	Decreases Expression	[45]
Protein pelota homolog (PELO)	OTF3WLIM	PELO_HUMAN	Decreases Expression	[44]
TIMELESS-interacting protein (TIPIN)	OT9PZHXV	TIPIN_HUMAN	Decreases Expression	[44]
tRNA pseudouridine(38/39) synthase (PUS3)	OT6WG6M2	PUS3_HUMAN	Decreases Expression	[44]
Transmembrane protein 185B (TMEM185B)	OTGNYS0J	T185B_HUMAN	Decreases Expression	[44]
Interferon-stimulated 20 kDa exonuclease-like 2 (ISG20L2)	OT3Q11WQ	I20L2_HUMAN	Decreases Expression	[44]
GrpE protein homolog 1, mitochondrial (GRPEL1)	OT8O00YJ	GRPE1_HUMAN	Decreases Expression	[44]
Protein CLN8 (CLN8)	OT0D4CB5	CLN8_HUMAN	Decreases Expression	[44]
Inactive cell surface hyaluronidase CEMIP2 (CEMIP2)	OT9I1XUO	CEIP2_HUMAN	Decreases Expression	[45]
rRNA methyltransferase 2, mitochondrial (MRM2)	OTRYA1HU	MRM2_HUMAN	Decreases Expression	[44]
ERBB receptor feedback inhibitor 1 (ERRFI1)	OT7VZ2IZ	ERRFI_HUMAN	Decreases Expression	[45]
Frizzled-1 (FZD1)	OTZATHVS	FZD1_HUMAN	Decreases Expression	[44]
RING finger protein 24 (RNF24)	OTUZI597	RNF24_HUMAN	Decreases Expression	[45]
DNA polymerase eta (POLH)	OTN07WXU	POLH_HUMAN	Increases Expression	[61]
5'-AMP-activated protein kinase subunit beta-1 (PRKAB1)	OT1OG4QZ	AAKB1_HUMAN	Increases Expression	[44]
V-type proton ATPase 116 kDa subunit a 2 (ATP6V0A2)	OTJBDX0Y	VPP2_HUMAN	Decreases Expression	[54]
Pleckstrin homology-like domain family A member 3 (PHLDA3)	OTXFUDO2	PHLA3_HUMAN	Increases Expression	[44]
Sestrin-1 (SESN1)	OTSFDZWL	SESN1_HUMAN	Increases Expression	[44]
Solute carrier family 22 member 4 (SLC22A4)	OT4LOVI9	S22A4_HUMAN	Increases Uptake	[49]
Organic cation/carnitine transporter 2 (SLC22A5)	OTC36TYB	S22A5_HUMAN	Increases Uptake	[49]
Protein artemis (DCLRE1C)	OTW3KB1I	DCR1C_HUMAN	Increases Response To Substance	[46]
Urea transporter 2 (SLC14A2)	OTYI6SX1	UT2_HUMAN	Increases Uptake	[49]

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