Details of the Drug Combination

General Information of Drug Combination (ID: DCLK7PY)

• Drug Combination Name: Sirolimus + Docetaxel
• Indication: Adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Sirolimus (DMGW1ID): Small molecular drug
  Docetaxel (DMDI269): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: OVCAR3
  Zero Interaction Potency (ZIP) Score: 4.79
  Bliss Independence Score: 8.71
  Loewe Additivity Score: 8
  LHighest Single Agent (HSA) Score: 6.36

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Sirolimus

Disease Entry	ICD 11	Status	REF
Advanced cancer	2A00-2F9Z	Approved	[2]
Brainstem neoplasm	N.A.	Approved	[2]
Graft-versus-host disease	4B24	Approved	[2]
Intracranial meningioma	N.A.	Approved	[2]
Lung cancer	2C25.0	Approved	[2]
Lung lymphangioleiomyomatosis	N.A.	Approved	[2]
Lymphangioleiomyomatosis	CB07	Approved	[3]
Mucosal melanoma	N.A.	Approved	[2]
Multiple myeloma	2A83	Approved	[4]
Multiple sclerosis	8A40	Approved	[2]
Non-small-cell lung cancer	2C25.Y	Approved	[2]
Organ transplant rejection	NE84	Approved	[5]
Plasma cell myeloma	2A83.1	Approved	[2]
Prostate cancer	2C82.0	Approved	[2]
Salivary gland squamous cell carcinoma	N.A.	Approved	[2]
Uveitis	9A96.Z	Phase 3	[6]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[7]
Dutch elm disease	8D64	Phase 1/2	[5]
Castration-resistant prostate carcinoma	N.A.	Investigative	[2]
Neuroblastoma	2D11.2	Investigative	[2]
Pancreatic acinar cell carcinoma	N.A.	Investigative	[2]
Polycystic kidney disease	GB8Y	Investigative	[2]
Rheumatoid arthritis	FA20	Investigative	[2]

Sirolimus Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Serine/threonine-protein kinase mTOR (mTOR)	TTCJG29	MTOR_HUMAN	Inhibitor	[10]
PI3K/AKT/mTOR pathway (PAm pathway)	TTGQUFK	NOUNIPROTAC	Inhibitor	[11]
HUMAN mammalian target of rapamycin (mTOR)	TT7HQAF	MTOR_HUMAN	Inhibitor	[12]

Sirolimus Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[13]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[14]

Sirolimus Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[15]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[16]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[16]

Sirolimus Interacts with 3 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Interleukin-2 (IL2)	OTGI4NSA	IL2_HUMAN	Increases ADR	[17]
Calcineurin subunit B type 1 (PPP3R1)	OTGQNFJQ	CANB1_HUMAN	Increases ADR	[17]
Nuclear receptor ROR-gamma (RORC)	OTUBFRPC	RORG_HUMAN	Increases ADR	[17]

Indication(s) of Docetaxel

Disease Entry	ICD 11	Status	REF
Advanced cancer	2A00-2F9Z	Approved	[8]
Breast carcinoma	N.A.	Approved	[8]
Head and neck cancer	2D42	Approved	[8]
Leiomyosarcoma	2B58	Approved	[8]
Lung cancer	2C25.0	Approved	[8]
Non-small-cell lung cancer	2C25.Y	Approved	[8]
Prostate adenocarcinoma	N.A.	Approved	[8]
Prostate cancer	2C82.0	Approved	[8]
Solid tumour/cancer	2A00-2F9Z	Approved	[9]
Urinary system neoplasm	N.A.	Approved	[8]
Gastric cancer	2B72	Investigative	[8]

Docetaxel Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tubulin (TUB)	TTML2WA	NOUNIPROTAC	Inhibitor	[21]

Docetaxel Interacts with 8 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[22]
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[23]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[24]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[25]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[26]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[27]
TAP-like protein (ABCB9)	DT68UV2	ABCB9_HUMAN	Substrate	[28]
Multidrug resistance-associated protein 7 (ABCC10)	DTPS120	MRP7_HUMAN	Substrate	[29]

Docetaxel Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[30]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[16]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[16]

Docetaxel Interacts with 83 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Response To Substance	[31]
ATP-binding cassette sub-family C member 2 (ABCC2)	OTJSIGV5	MRP2_HUMAN	Increases ADR	[32]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Increases Expression	[33]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Response To Substance	[31]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[34]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[35]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Expression	[36]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases Expression	[36]
Progesterone receptor (PGR)	OT0FZ3QE	PRGR_HUMAN	Decreases Expression	[36]
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Expression	[36]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Increases Expression	[36]
Dihydropyrimidine dehydrogenase (DPYD)	OTWRF2NR	DPYD_HUMAN	Decreases Activity	[18]
Tumor necrosis factor receptor superfamily member 10A (TNFRSF10A)	OTBPCU2O	TR10A_HUMAN	Increases Expression	[37]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[37]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Degradation	[38]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Activity	[39]
PC4 and SFRS1-interacting protein (PSIP1)	OT4YAFUS	PSIP1_HUMAN	Increases Cleavage	[40]
RAF proto-oncogene serine/threonine-protein kinase (RAF1)	OT51LSFO	RAF1_HUMAN	Increases Expression	[41]
Granulocyte-macrophage colony-stimulating factor (CSF2)	OT1M7D28	CSF2_HUMAN	Increases Secretion	[42]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[19]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Phosphorylation	[43]
Protein kinase C beta type (PRKCB)	OTYQ0656	KPCB_HUMAN	Increases Phosphorylation	[44]
Keratin, type I cytoskeletal 18 (KRT18)	OTVLQFIP	K1C18_HUMAN	Increases Expression	[45]
Cyclin-dependent kinase 1 (CDK1)	OTW1SC2N	CDK1_HUMAN	Increases Activity	[46]
Prostate-specific antigen (KLK3)	OTFGSBFJ	KLK3_HUMAN	Decreases Expression	[47]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[43]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Decreases Expression	[48]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[49]
Natriuretic peptides B (NPPB)	OTSN2IPY	ANFB_HUMAN	Increases Expression	[50]
Cyclic AMP-dependent transcription factor ATF-3 (ATF3)	OTC1UOHP	ATF3_HUMAN	Decreases Expression	[51]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A)	OTDRV63V	GA45A_HUMAN	Decreases Expression	[51]
Cyclin-dependent kinase 2 (CDK2)	OTB5DYYZ	CDK2_HUMAN	Increases Activity	[46]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[52]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[41]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[41]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Phosphorylation	[20]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Decreases Expression	[51]
Signal transducer and activator of transcription 3 (STAT3)	OTAAGKYZ	STAT3_HUMAN	Decreases Phosphorylation	[53]
Caspase-2 (CASP2)	OTUDYSPP	CASP2_HUMAN	Increases Activity	[40]
Cyclin-dependent kinase inhibitor 2A (CDKN2A)	OTN0ZWAE	CDN2A_HUMAN	Decreases Expression	[54]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Decreases Expression	[34]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[55]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[56]
E3 ubiquitin-protein ligase Mdm2 (MDM2)	OTOVXARF	MDM2_HUMAN	Increases Expression	[19]
Focal adhesion kinase 1 (PTK2)	OT3Q1JDY	FAK1_HUMAN	Increases Cleavage	[57]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[58]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Increases Expression	[38]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[57]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Increases Activity	[38]
Bcl2-associated agonist of cell death (BAD)	OT63ERYM	BAD_HUMAN	Decreases Phosphorylation	[38]
ELL-associated factor 2 (EAF2)	OTSOET5L	EAF2_HUMAN	Decreases Expression	[51]
Small integral membrane protein 14 (SMIM14)	OT47IF19	SIM14_HUMAN	Decreases Expression	[51]
Protein FAM117A (FAM117A)	OT2FBGGV	F117A_HUMAN	Decreases Expression	[51]
Delta-like protein 4 (DLL4)	OTRA4K2V	DLL4_HUMAN	Increases Expression	[55]
Tumor necrosis factor receptor superfamily member 19 (TNFRSF19)	OTTVT4MB	TNR19_HUMAN	Decreases Expression	[51]
Tropomodulin-2 (TMOD2)	OTTTUH2W	TMOD2_HUMAN	Decreases Expression	[51]
Flavin-containing monooxygenase 3 (FMO3)	OT1G2EV3	FMO3_HUMAN	Affects Response To Substance	[59]
Kinesin heavy chain isoform 5A (KIF5A)	OT3ETTI6	KIF5A_HUMAN	Decreases Response To Substance	[60]
Proteinase-activated receptor 1 (F2R)	OT4WVWBO	PAR1_HUMAN	Decreases Response To Substance	[61]
ATP-binding cassette sub-family G member 1 (ABCG1)	OT5BG6MK	ABCG1_HUMAN	Affects Response To Substance	[59]
Regulator of G-protein signaling 17 (RGS17)	OT5RVUDS	RGS17_HUMAN	Increases Response To Substance	[62]
Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B)	OT8KME51	BUB1B_HUMAN	Affects Response To Substance	[63]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Decreases Response To Substance	[64]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Response To Substance	[65]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Decreases Response To Substance	[66]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Affects Response To Substance	[59]
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Increases Response To Substance	[31]
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Increases Response To Substance	[67]
Kinesin-like protein KIFC3 (KIFC3)	OTOPD4QO	KIFC3_HUMAN	Decreases Response To Substance	[60]
Regulator of G-protein signaling 10 (RGS10)	OTQ8N1QH	RGS10_HUMAN	Increases Response To Substance	[62]
E3 ubiquitin-protein ligase CHFR (CHFR)	OTRAD2TT	CHFR_HUMAN	Decreases Response To Substance	[68]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Response To Substance	[69]
Cell surface glycoprotein MUC18 (MCAM)	OTT8XKGE	MUC18_HUMAN	Decreases Response To Substance	[70]
Kinesin-like protein KIF12 (KIF12)	OTTALNDD	KIF12_HUMAN	Decreases Response To Substance	[60]
Nucleophosmin (NPM1)	OTTBYYT0	NPM_HUMAN	Decreases Response To Substance	[71]
Flavin-containing monooxygenase 2 (FMO2)	OTUJUL9S	FMO2_HUMAN	Affects Response To Substance	[59]
NADPH--cytochrome P450 reductase (POR)	OTVIDOCH	NCPR_HUMAN	Increases Response To Substance	[31]
Kinesin-like protein KIF14 (KIF14)	OTXHT4JM	KIF14_HUMAN	Decreases Response To Substance	[72]
Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1)	OTXNGZCG	MD2L1_HUMAN	Affects Response To Substance	[63]
Cellular retinoic acid-binding protein 2 (CRABP2)	OTY01V9G	RABP2_HUMAN	Affects Response To Substance	[73]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Affects Response To Substance	[74]
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Affects Response To Substance	[59]
ATP-binding cassette sub-family C member 6 (ABCC6)	OTZT0LKT	MRP6_HUMAN	Affects Response To Substance	[59]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult acute myeloid leukemia	DCWA53B	HL-60(TB)	Investigative	[75]
Astrocytoma	DCJSDSY	U251	Investigative	[75]
Chronic myelogenous leukemia	DCBSFSP	K-562	Investigative	[75]
Clear cell renal cell carcinoma	DCXKPNV	A498	Investigative	[75]
Clear cell renal cell carcinoma	DCYYZIW	TK-10	Investigative	[75]
Colon adenocarcinoma	DC1PSUA	COLO 205	Investigative	[76]
Colon carcinoma	DCF70NK	KM12	Investigative	[76]
Invasive ductal carcinoma	DCBTY2J	T-47D	Investigative	[76]
Adenocarcinoma	DCOW7RM	DU-145	Investigative	[1]
Adenocarcinoma	DCY02V0	A549	Investigative	[1]
Adenocarcinoma	DC8ZNH5	HT29	Investigative	[1]
Adenocarcinoma	DC845ZU	HCT116	Investigative	[1]
Amelanotic melanoma	DCMZYRP	MDA-MB-435	Investigative	[1]
Cutaneous melanoma	DCW5LD9	SK-MEL-5	Investigative	[1]
High grade ovarian serous adenocarcinoma	DC6ZYWG	OVCAR-8	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCHFDIF	OVCAR-5	Investigative	[1]
Large cell lung carcinoma	DCZGZWG	NCI-H460	Investigative	[1]
Malignant melanoma	DCZ986H	UACC62	Investigative	[1]
Minimally invasive lung adenocarcinoma	DCEZJCM	NCI-H322M	Investigative	[1]
Prostate carcinoma	DCQ0IS4	PC-3	Investigative	[1]

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