Details of the Drug Combination

General Information of Drug Combination (ID: DCEMT1F)

• Drug Combination Name: Carfilzomib + Tacrolimus
• Indication: Hematologic Malignancies; Status: Phase 1 [1]
• Component Drugs:
  Carfilzomib (DM48K0X): Small molecular drug
  Tacrolimus (DMZ7XNQ): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Carfilzomib

Disease Entry	ICD 11	Status	REF
Multiple myeloma	2A83	Approved	[2]
Plasma cell myeloma	2A83.1	Approved	[3]
Small-cell lung cancer	2C25.Y	Phase 1/2	[4]

Carfilzomib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Proteasome (PS)	TTU7ZMG	NOUNIPROTAC	Modulator	[8]

Carfilzomib Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[9]

Carfilzomib Interacts with 8 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Decreases Activity	[10]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Activity	[11]
Cytochrome c oxidase subunit 8A, mitochondrial (COX8A)	OTU0NR39	COX8A_HUMAN	Decreases Expression	[11]
Basigin (BSG)	OTD0CVEC	BASI_HUMAN	Decreases Expression	[12]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Cleavage	[12]
C-X-C chemokine receptor type 4 (CXCR4)	OTUFSBX2	CXCR4_HUMAN	Decreases Expression	[12]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Increases Activity	[11]
Breast cancer type 1 susceptibility protein (BRCA1)	OT5BN6VH	BRCA1_HUMAN	Increases Response To Substance	[13]

Indication(s) of Tacrolimus

Disease Entry	ICD 11	Status	REF
Graft-versus-host disease	4B24	Approved	[5]
Hepatosplenic T-cell lymphoma	N.A.	Approved	[5]
Kidney transplant rejection	NE84	Approved	[5]
Large granular lymphocytic leukemia	2A90.1	Approved	[5]
Leukemia	N.A.	Approved	[5]
Lupus nephritis	4A40.0Y	Approved	[5]
MALT lymphoma	N.A.	Approved	[5]
Myeloproliferative neoplasm	2A20	Approved	[5]
Nodal marginal zone lymphoma	2A85.0	Approved	[5]
Organ transplant rejection	NE84	Approved	[6]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	N.A.	Approved	[5]
Recurrent adult burkitt lymphoma	2A85.6	Approved	[5]
Small intestine lymphoma	N.A.	Approved	[5]
Splenic marginal zone lymphoma	N.A.	Approved	[5]
Testicular lymphoma	N.A.	Approved	[5]
Ocular allergy	4A81	Phase 3	[6]
Classic Hodgkin lymphoma	N.A.	Investigative	[5]

Tacrolimus Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Calcineurin (PPP3CA)	TTA4LDE	PP2BA_HUMAN	Inhibitor	[16]

Tacrolimus Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[17]

Tacrolimus Interacts with 5 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[18]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[19]
NADPH-cytochrome P450 reductase (CPR)	DE3N2FM	NCPR_HUMAN	Metabolism	[20]
Ribosomal 23S RNA methyltransferase Erm (erm)	DEW6V07	A0A5N1AHF6_CORAY	Metabolism	[21]
Ribosomal 23S RNA methyltransferase Erm (erm)	DEA65D8	A0A381KDL2_CORJE	Metabolism	[21]

Tacrolimus Interacts with 49 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Decreases Methylation	[22]
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Decreases Methylation	[22]
NADPH--cytochrome P450 reductase (POR)	OTVIDOCH	NCPR_HUMAN	Affects Response To Substance	[23]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Response To Substance	[24]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Increases Expression	[25]
Cytochrome b-245 light chain (CYBA)	OT16N9ZO	CY24A_HUMAN	Increases Expression	[25]
Nitric oxide synthase 3 (NOS3)	OTLDT7NR	NOS3_HUMAN	Increases Expression	[25]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[26]
Natural cytotoxicity triggering receptor 3 (NCR3)	OT20M764	NCTR3_HUMAN	Increases Expression	[27]
Hepatocyte growth factor-regulated tyrosine kinase substrate (HGS)	OTCYYCAC	HGS_HUMAN	Increases Expression	[15]
Rho guanine nucleotide exchange factor 11 (ARHGEF11)	OTDOMEH6	ARHGB_HUMAN	Increases Expression	[15]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[28]
Actin-related protein 2/3 complex subunit 5 (ARPC5)	OTFNMMDL	ARPC5_HUMAN	Increases Expression	[15]
G2/mitotic-specific cyclin-B2 (CCNB2)	OTIEXTDK	CCNB2_HUMAN	Decreases Expression	[28]
Zinc finger protein SNAI1 (SNAI1)	OTDPYAMC	SNAI1_HUMAN	Increases Expression	[14]
Insulin (INS)	OTZ85PDU	INS_HUMAN	Decreases Expression	[29]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Secretion	[30]
Interferon gamma (IFNG)	OTXG9JM7	IFNG_HUMAN	Decreases Expression	[31]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Expression	[32]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Increases Expression	[33]
Fibronectin (FN1)	OTB5ZN4Q	FINC_HUMAN	Increases Expression	[33]
Granulocyte-macrophage colony-stimulating factor (CSF2)	OT1M7D28	CSF2_HUMAN	Decreases Expression	[31]
Interleukin-4 (IL4)	OTOXBWAU	IL4_HUMAN	Decreases Expression	[31]
Interleukin-5 (IL5)	OTAFPSCO	IL5_HUMAN	Decreases Expression	[34]
Interleukin-3 (IL3)	OT0CQ35N	IL3_HUMAN	Decreases Expression	[31]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[35]
Cadherin-1 (CDH1)	OTFJMXPM	CADH1_HUMAN	Decreases Expression	[14]
C-C motif chemokine 5 (CCL5)	OTSCA5CK	CCL5_HUMAN	Decreases Expression	[34]
Ras-related protein Rab-4A (RAB4A)	OT7BL9WW	RAB4A_HUMAN	Increases Expression	[15]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Decreases Degradation	[30]
T-lymphocyte activation antigen CD80 (CD80)	OTJBLUQE	CD80_HUMAN	Decreases Expression	[36]
T-lymphocyte activation antigen CD86 (CD86)	OTJCSBPC	CD86_HUMAN	Decreases Expression	[36]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Cleavage	[37]
Troponin T, cardiac muscle (TNNT2)	OT80NN7R	TNNT2_HUMAN	Increases Expression	[38]
Tumor necrosis factor ligand superfamily member 6 (FASLG)	OTZARCHH	TNFL6_HUMAN	Decreases Secretion	[39]
Glycogen synthase kinase-3 alpha (GSK3A)	OT0F6DWV	GSK3A_HUMAN	Increases Phosphorylation	[14]
Glycogen synthase kinase-3 beta (GSK3B)	OTL3L14B	GSK3B_HUMAN	Increases Phosphorylation	[14]
Eotaxin (CCL11)	OT3BIFPK	CCL11_HUMAN	Decreases Expression	[34]
C-C chemokine receptor type 3 (CCR3)	OT6GBUFA	CCR3_HUMAN	Decreases Expression	[34]
LIM domain kinase 1 (LIMK1)	OTFZ8MZ0	LIMK1_HUMAN	Increases Expression	[15]
Interleukin-2 (IL2)	OTGI4NSA	IL2_HUMAN	Decreases Expression	[31]
Neutrophil gelatinase-associated lipocalin (LCN2)	OTSB42BR	NGAL_HUMAN	Increases Expression	[33]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[37]
Lethal(2) giant larvae protein homolog 1 (LLGL1)	OTAIQSXZ	L2GL1_HUMAN	Increases Expression	[15]
Calcineurin subunit B type 1 (PPP3R1)	OTGQNFJQ	CANB1_HUMAN	Increases ADR	[40]
Catalase (CAT)	OTHEBX9R	CATA_HUMAN	Decreases Response To Substance	[41]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Response To Substance	[41]
Peroxisome proliferator-activated receptor alpha (PPARA)	OTK095PP	PPARA_HUMAN	Affects Response To Substance	[23]
Cytochrome P450 3A7 (CYP3A7)	OTTCDHHM	CP3A7_HUMAN	Decreases Methylation	[22]

References

• [1] ClinicalTrials.gov (NCT02145403) Phase 1/2 Study of Carfilzomib for the Prevention of Relapse and GVHD in Allo-HCT for Hematologic Malignancies
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• [3] Carfilzomib FDA Label
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] Tacrolimus FDA Label
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