General Information of Drug Combination (ID: DCUSBEL)

Drug Combination Name
Sitagliptin Pamidronate
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Sitagliptin   DMGDKXN Pamidronate   DMB4AVP
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 13.69
Bliss Independence Score: 13.69
Loewe Additivity Score: 27.68
LHighest Single Agent (HSA) Score: 27.7

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Sitagliptin
Disease Entry ICD 11 Status REF
Cystic fibrosis CA25 Approved [2]
Non-insulin dependent diabetes 5A11 Approved [2]
Renal hypoplasia N.A. Approved [2]
Type-2 diabetes 5A11 Approved [3]
Peripheral arterial disease BD4Z Phase 1/2 [4]
Sitagliptin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Dipeptidyl peptidase 4 (DPP-4) TTDIGC1 DPP4_HUMAN Inhibitor [7]
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Sitagliptin Interacts with 3 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [8]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [9]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [10]
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Sitagliptin Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [11]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [11]
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Indication(s) of Pamidronate
Disease Entry ICD 11 Status REF
Bone Paget disease N.A. Approved [5]
Hypercalcaemia 5B91.0 Approved [6]
Pamidronate Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Geranyltranstransferase (FDPS) TTIKWV4 FPPS_HUMAN Inhibitor [12]
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Pamidronate Interacts with 18 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
C-reactive protein (CRP) OT0RFT8F CRP_HUMAN Decreases Expression [13]
Osteocalcin (BGLAP) OTK1YLWQ OSTCN_HUMAN Increases Expression [13]
Alkaline phosphatase, tissue-nonspecific isozyme (ALPL) OTG7J4BP PPBT_HUMAN Increases Expression [13]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Decreases Expression [13]
Beta-2-microglobulin (B2M) OTDWN6NX B2MG_HUMAN Decreases Expression [13]
Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B) OTQ4W7MT TR11B_HUMAN Increases Expression [14]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Expression [15]
Collagen alpha-1(I) chain (COL1A1) OTI31178 CO1A1_HUMAN Decreases Expression [16]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [17]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [17]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Expression [18]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [18]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [18]
Transforming protein RhoA (RHOA) OT6YOJ9N RHOA_HUMAN Decreases Expression [18]
Ras-related protein Rap-1A (RAP1A) OT5RH6TI RAP1A_HUMAN Decreases Prenylation [19]
Rho-associated protein kinase 1 (ROCK1) OTSXYVW1 ROCK1_HUMAN Decreases Expression [18]
Fibroblast growth factor 23 (FGF23) OTZT523D FGF23_HUMAN Decreases Expression [20]
Bcl-2-interacting killer (BIK) OTTH1T3D BIK_HUMAN Increases Response To Substance [21]
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⏷ Show the Full List of 18 DOT(s)

References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2 Sitagliptin FDA Label
3 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: 6286).
4 ClinicalTrials.gov (NCT01619332) Clinical Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LEZ763. U.S. National Institutes of Health.
5 Pamidronate FDA Label
6 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: 7259).
7 Novel therapeutics for type 2 diabetes: incretin hormone mimetics (glucagon-like peptide-1 receptor agonists) and dipeptidyl peptidase-4 inhibitors. Pharmacol Ther. 2009 Oct;124(1):113-38.
8 Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
9 265 effect of dietary cholesterol on gallbladder bile lithogenicity and gene expression in the enterohepatic axis of non-obese gallstone and control women. Journal of Hepatology, 2009, 50(09):S105-S106.
10 Transport of the dipeptidyl peptidase-4 inhibitor sitagliptin by human organic anion transporter 3, organic anion transporting polypeptide 4C1, and multidrug resistance P-glycoprotein. J Pharmacol Exp Ther. 2007 May;321(2):673-83.
11 Pharmacokinetics of dipeptidylpeptidase-4 inhibitors. Diabetes Obes Metab. 2010 Aug;12(8):648-58.
12 Detection of nonsterol isoprenoids by HPLC-MS/MS. Anal Biochem. 2008 Dec 1;383(1):18-24.
13 Pamidronate increases markers of bone formation in patients with multiple myeloma in plateau phase under interferon-alpha treatment. Calcif Tissue Int. 2001 May;68(5):285-90.
14 Bisphosphonates pamidronate and zoledronic acid stimulate osteoprotegerin production by primary human osteoblasts. Biochem Biophys Res Commun. 2002 Mar 1;291(3):680-6. doi: 10.1006/bbrc.2002.6510.
15 An in vitro and in vivo study of cytokines in the acute-phase response associated with bisphosphonates. Calcif Tissue Int. 1997 Nov;61(5):386-92. doi: 10.1007/s002239900353.
16 Expression profile and synthesis of different collagen types I, II, III, and V of human gingival fibroblasts, osteoblasts, and SaOS-2 cells after bisphosphonate treatment. Clin Oral Investig. 2010 Feb;14(1):51-8. doi: 10.1007/s00784-009-0312-2. Epub 2009 Jul 14.
17 Bisphosphonates induce apoptosis in human breast cancer cell lines. Br J Cancer. 2000 Apr;82(8):1459-68. doi: 10.1054/bjoc.1999.1131.
18 Pamidronate induced anti-proliferative, apoptotic, and anti-migratory effects in hepatocellular carcinoma. J Hepatol. 2006 Jan;44(1):142-50. doi: 10.1016/j.jhep.2005.09.022. Epub 2005 Nov 9.
19 Nitrogen-containing bisphosphonates induce apoptosis of Caco-2 cells in vitro by inhibiting the mevalonate pathway: a model of bisphosphonate-induced gastrointestinal toxicity. Bone. 2001 Oct;29(4):336-43. doi: 10.1016/s8756-3282(01)00589-0.
20 The role of fibroblast growth factor 23 for hypophosphatemia and abnormal regulation of vitamin D metabolism in patients with McCune-Albright syndrome. J Bone Miner Metab. 2005;23(3):231-7. doi: 10.1007/s00774-004-0589-9.
21 Caspase-independent induction of apoptosis in human melanoma cells by the proapoptotic Bcl-2-related protein Nbk / Bik. Oncogene. 2005 Nov 10;24(49):7369-80. doi: 10.1038/sj.onc.1208890.