General Information of Drug Combination (ID: DCM6N9B)

Drug Combination Name
Lovastatin Colestipol
Indication
Disease Entry Status REF
Cardiovascular Diseases Phase 1 [1]
Component Drugs Lovastatin   DM9OZWQ Colestipol   DMIRPD8
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL is unavailable

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Lovastatin
Disease Entry ICD 11 Status REF
Arteriosclerosis BD40 Approved [2]
Hypercholesterolaemia 5C80.0 Approved [3]
Hyperlipidemia 5C80.Z Approved [2]
Hyperlipidemia, familial combined, LPL related N.A. Approved [2]
Hypertriglyceridemia 5C80.1 Approved [2]
Melanoma 2C30 Approved [2]
X-linked chondrodysplasia punctata 2 N.A. Approved [2]
Cardiovascular disease BA00-BE2Z Phase 3 [4]
Smith-Lemli-Opitz syndrome N.A. Investigative [2]
Lovastatin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
HMG-CoA reductase (HMGCR) TTPADOQ HMDH_HUMAN Inhibitor [7]
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Lovastatin Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [8]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [9]
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Lovastatin Interacts with 7 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [10]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [11]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [11]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [11]
UDP-glucuronosyltransferase 2B7 (UGT2B7) DEB3CV1 UD2B7_HUMAN Metabolism [11]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DEF2WXN UD13_HUMAN Metabolism [11]
Serum paraoxonase/lactonase 3 (PON3) DETXQZ1 PON3_HUMAN Metabolism [12]
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⏷ Show the Full List of 7 DME(s)
Lovastatin Interacts with 73 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2C8 (CYP2C8) OTHCWT42 CP2C8_HUMAN Decreases Activity [13]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [14]
Serum paraoxonase/lactonase 3 (PON3) OT80W9TA PON3_HUMAN Increases Hydrolysis [15]
Solute carrier organic anion transporter family member 1B1 (SLCO1B1) OTNEN8QK SO1B1_HUMAN Decreases Activity [16]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Transport [16]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) OTRT3F3U HMDH_HUMAN Increases Expression [17]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [18]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Activity [19]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Activity [20]
Squalene synthase (FDFT1) OTGDISIT FDFT_HUMAN Increases Activity [21]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Decreases Activity [16]
Insulin-induced gene 1 protein (INSIG1) OTZF5X1D INSI1_HUMAN Increases Expression [17]
Phospholipid-transporting ATPase ABCA1 (ABCA1) OT94G6BQ ABCA1_HUMAN Increases Expression [17]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [22]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [23]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Increases Expression [24]
GTPase NRas (NRAS) OTVQ1DG3 RASN_HUMAN Decreases Prenylation [25]
GTPase HRas (HRAS) OTWQN0DP RASH_HUMAN Decreases Prenylation [25]
GTPase KRas (KRAS) OT78QCN8 RASK_HUMAN Decreases Prenylation [25]
Low-density lipoprotein receptor (LDLR) OTH559LU LDLR_HUMAN Increases Expression [26]
Thyroglobulin (TG) OT3ELHIJ THYG_HUMAN Increases Secretion [27]
RAF proto-oncogene serine/threonine-protein kinase (RAF1) OT51LSFO RAF1_HUMAN Decreases Activity [28]
Apolipoprotein B-100 (APOB) OTH0UOCZ APOB_HUMAN Decreases Secretion [26]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [29]
Amyloid-beta precursor protein (APP) OTKFD7R4 A4_HUMAN Increases Cleavage [30]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Phosphorylation [31]
Tyrosine 3-monooxygenase (TH) OT6ZORKP TY3H_HUMAN Increases Expression [32]
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Decreases Expression [28]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [33]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [18]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [34]
Matrix metalloproteinase-9 (MMP9) OTB2QDAV MMP9_HUMAN Decreases Expression [28]
CD44 antigen (CD44) OT9TTJ41 CD44_HUMAN Decreases Expression [29]
Neuromodulin (GAP43) OT2OTGGV NEUM_HUMAN Increases Expression [32]
Lamin-B1 (LMNB1) OT100T3P LMNB1_HUMAN Decreases Farnesylation [35]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [36]
Cyclin-dependent kinase 2 (CDK2) OTB5DYYZ CDK2_HUMAN Decreases Activity [31]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Activity [28]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Activity [28]
G1/S-specific cyclin-D3 (CCND3) OTNKPQ22 CCND3_HUMAN Decreases Expression [31]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [37]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Increases Expression [18]
Sterol regulatory element-binding protein 1 (SREBF1) OTWBRPAI SRBP1_HUMAN Increases Expression [38]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Affects Localization [18]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [36]
Caspase-2 (CASP2) OTUDYSPP CASP2_HUMAN Increases Activity [19]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Increases Expression [31]
Fatty acid synthase (FASN) OTFII9KG FAS_HUMAN Increases Expression [26]
Centromere protein F (CENPF) OT7AG0SW CENPF_HUMAN Increases Expression [39]
Glycogen synthase kinase-3 beta (GSK3B) OTL3L14B GSK3B_HUMAN Decreases Phosphorylation [40]
Tumor necrosis factor ligand superfamily member 10 (TNFSF10) OT4PXBTA TNF10_HUMAN Increases Response To Substance [41]
Caspase-6 (CASP6) OTXLD3EC CASP6_HUMAN Increases Activity [42]
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) OTOWDUNT PTEN_HUMAN Increases Expression [37]
Cell division control protein 42 homolog (CDC42) OT5QBC5M CDC42_HUMAN Increases Expression [24]
Transforming protein RhoA (RHOA) OT6YOJ9N RHOA_HUMAN Decreases Prenylation [25]
Actin, aortic smooth muscle (ACTA2) OTEDLG8E ACTA_HUMAN Decreases Expression [43]
Rho-related GTP-binding protein RhoB (RHOB) OTHQFQF7 RHOB_HUMAN Decreases Prenylation [25]
Ras-related protein Rap-1A (RAP1A) OT5RH6TI RAP1A_HUMAN Increases Expression [39]
Ras-related C3 botulinum toxin substrate 1 (RAC1) OTKRO61U RAC1_HUMAN Decreases Activity [28]
HLA class II histocompatibility antigen, DR beta 3 chain (HLA-DRB3) OT5PM9N7 DRB3_HUMAN Affects Expression [44]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [34]
Sterol regulatory element-binding protein 2 (SREBF2) OTBXUNPL SRBP2_HUMAN Increases Localization [26]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Affects Activity [45]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [46]
Lymphoid enhancer-binding factor 1 (LEF1) OTWS5I5H LEF1_HUMAN Affects Localization [40]
A-kinase anchor protein 7 isoforms alpha and beta (AKAP7) OT0L3PZ6 AKA7A_HUMAN Decreases Response To Substance [47]
Beta-parvin (PARVB) OT9OGVWX PARVB_HUMAN Decreases Response To Substance [47]
Metalloreductase STEAP2 (STEAP2) OTGE9ETG STEA2_HUMAN Decreases Response To Substance [47]
Interleukin-2 (IL2) OTGI4NSA IL2_HUMAN Increases ADR [48]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases ADR [48]
Phosphatidate phosphatase LPIN2 (LPIN2) OTRRTMXX LPIN2_HUMAN Decreases Response To Substance [47]
ELL-associated factor 2 (EAF2) OTSOET5L EAF2_HUMAN Decreases Response To Substance [47]
Ankyrin-2 (ANK2) OTWB4R1Y ANK2_HUMAN Decreases Response To Substance [47]
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⏷ Show the Full List of 73 DOT(s)
Indication(s) of Colestipol
Disease Entry ICD 11 Status REF
Hypercholesterolaemia 5C80.0 Approved [5]
Hyperlipidemia 5C80.Z Approved [5]
Primary hypercholesterolemia 5C80.00 Approved [6]

References

1 ClinicalTrials.gov (NCT00000512) Familial Atherosclerosis Treatment Study
2 Lovastatin 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: 2739).
4 Clinical pipeline report, company report or official report of CardioPharma Wilmington.
5 Colestipol FDA Label
6 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
7 Microarray and biochemical analysis of lovastatin-induced apoptosis of squamous cell carcinomas. Neoplasia. 2002 Jul-Aug;4(4):337-46.
8 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.
9 A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. J Biol Chem. 1999 Dec 24;274(52):37161-8.
10 Metabolic interactions with statins. Tidsskr Nor Laegeforen. 2001 Jan 20;121(2):189-93.
11 Pharmacogenomics of statins: understanding susceptibility to adverse effects. Pharmgenomics Pers Med. 2016 Oct 3;9:97-106.
12 Paraoxonases-1, -2 and -3: what are their functions? Chem Biol Interact. 2016 Nov 25;259(Pt B):51-62.
13 Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78.
14 Receptor-dependent regulation of the CYP3A4 gene. Toxicology. 2002 Dec 27;181-182:199-202.
15 Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities. J Lipid Res. 2005 Jun;46(6):1239-47. doi: 10.1194/jlr.M400511-JLR200. Epub 2005 Mar 16.
16 Differential interaction of 3-hydroxy-3-methylglutaryl-coa reductase inhibitors with ABCB1, ABCC2, and OATP1B1. Drug Metab Dispos. 2005 Apr;33(4):537-46.
17 Desmosterol can replace cholesterol in sustaining cell proliferation and regulating the SREBP pathway in a sterol-Delta24-reductase-deficient cell line. Biochem J. 2009 May 13;420(2):305-15.
18 Lovastatin lactone elicits human lung cancer cell apoptosis via a COX-2/PPAR-dependent pathway. Oncotarget. 2016 Mar 1;7(9):10345-62. doi: 10.18632/oncotarget.7213.
19 Lovastatin induces apoptosis of anaplastic thyroid cancer cells via inhibition of protein geranylgeranylation and de novo protein synthesis. Endocrinology. 2003 Sep;144(9):3852-9. doi: 10.1210/en.2003-0098.
20 Statins activate the mitochondrial pathway of apoptosis in human lymphoblasts and myeloma cells. Carcinogenesis. 2005 May;26(5):883-91. doi: 10.1093/carcin/bgi036. Epub 2005 Feb 10.
21 Pravastatin inhibited the cholesterol synthesis in human hepatoma cell line Hep G2 less than simvastatin and lovastatin, which is reflected in the upregulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase and squalene synthase. Biochem Pharmacol. 1993 Jun 9;45(11):2203-8.
22 A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
23 Survivin down-regulation plays a crucial role in 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor-induced apoptosis in cancer. J Biol Chem. 2007 Jul 6;282(27):19273-81. doi: 10.1074/jbc.M610350200. Epub 2007 May 1.
24 Statins induce apoptosis in ovarian cancer cells through activation of JNK and enhancement of Bim expression. Cancer Chemother Pharmacol. 2009 May;63(6):997-1005. doi: 10.1007/s00280-008-0830-7. Epub 2008 Sep 3.
25 Combining prenylation inhibitors causes synergistic cytotoxicity, apoptosis and disruption of RAS-to-MAP kinase signalling in multiple myeloma cells. Br J Haematol. 2005 Sep;130(6):912-25. doi: 10.1111/j.1365-2141.2005.05696.x.
26 Effect of atorvastatin, simvastatin, and lovastatin on the metabolism of cholesterol and triacylglycerides in HepG2 cells. Biochem Pharmacol. 2001 Dec 1;62(11):1545-55. doi: 10.1016/s0006-2952(01)00790-0.
27 Lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, induces apoptosis and differentiation in human anaplastic thyroid carcinoma cells. J Clin Endocrinol Metab. 2003 Jul;88(7):3021-6. doi: 10.1210/jc.2002-021834.
28 Simvastatin and lovastatin inhibit breast cell invasion induced by H-Ras. Oncol Rep. 2009 May;21(5):1317-22. doi: 10.3892/or_00000357.
29 Simvastatin prevents skeletal metastasis of breast cancer by an antagonistic interplay between p53 and CD44. J Biol Chem. 2011 Apr 1;286(13):11314-27. doi: 10.1074/jbc.M110.193714. Epub 2011 Jan 3.
30 Protection against the Neurotoxic Effects of -Amyloid Peptide on Cultured Neuronal Cells by Lovastatin Involves Elevated Expression of 7 Nicotinic Acetylcholine Receptors and Activating Phosphorylation of Protein Kinases. Am J Pathol. 2018 Apr;188(4):1081-1093. doi: 10.1016/j.ajpath.2017.11.020. Epub 2018 Jan 16.
31 Lovastatin inhibits G1/S transition of normal human B-lymphocytes independent of apoptosis. Exp Cell Res. 1999 Oct 10;252(1):144-53. doi: 10.1006/excr.1999.4608.
32 Lovastatin induces neuronal differentiation and apoptosis of embryonal carcinoma and neuroblastoma cells: enhanced differentiation and apoptosis in combination with dbcAMP. Mol Cell Biochem. 2010 Dec;345(1-2):1-11. doi: 10.1007/s11010-010-0553-z. Epub 2010 Aug 9.
33 Simvastatin-dependent up-regulation of heme oxygenase-1 via mRNA stabilization in human endothelial cells. Eur J Pharm Sci. 2010 Sep 11;41(1):118-24. doi: 10.1016/j.ejps.2010.05.021. Epub 2010 Jun 8.
34 Lovastatin augments apoptosis induced by chemotherapeutic agents in colon cancer cells. Clin Cancer Res. 1999 Aug;5(8):2223-9.
35 Apoptosis and cell-cycle arrest in human and murine tumor cells are initiated by isoprenoids. J Nutr. 1999 Apr;129(4):804-13. doi: 10.1093/jn/129.4.804.
36 In vitro mechanisms of lovastatin on lung cancer cell lines as a potential chemopreventive agent. Lung. 2008 Jan-Feb;186(1):45-54. doi: 10.1007/s00408-007-9053-7. Epub 2007 Nov 22.
37 Increased PTEN expression due to transcriptional activation of PPARgamma by Lovastatin and Rosiglitazone. Int J Cancer. 2006 May 15;118(10):2390-8. doi: 10.1002/ijc.21799.
38 Indirect co-cultivation of HepG2 with differentiated THP-1 cells induces AHR signalling and release of pro-inflammatory cytokines. Toxicol In Vitro. 2020 Oct;68:104957. doi: 10.1016/j.tiv.2020.104957. Epub 2020 Jul 30.
39 Synergistic interaction of lovastatin and paclitaxel in human cancer cells. Mol Cancer Ther. 2001 Dec;1(2):141-9.
40 Lovastatin protects human neurons against Abeta-induced toxicity and causes activation of beta-catenin-TCF/LEF signaling. Neurosci Lett. 2007 Feb 2;412(3):211-6. doi: 10.1016/j.neulet.2006.07.045. Epub 2007 Jan 17.
41 Lovastatin sensitized human glioblastoma cells to TRAIL-induced apoptosis. J Neurooncol. 2008 Feb;86(3):273-83. doi: 10.1007/s11060-007-9475-3. Epub 2007 Oct 11.
42 Lovastatin-induced apoptosis in thyroid cells: involvement of cytochrome c and lamin B. Eur J Endocrinol. 2001 Nov;145(5):645-50. doi: 10.1530/eje.0.1450645.
43 Inhibitory effects of clinical reagents having anti-oxidative activity on transforming growth factor-1-induced expression of -smooth muscle actin in human fetal lung fibroblasts. J Toxicol Sci. 2011;36(6):733-40. doi: 10.2131/jts.36.733.
44 Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
45 Comparative evaluation of HERG currents and QT intervals following challenge with suspected torsadogenic and nontorsadogenic drugs. J Pharmacol Exp Ther. 2006 Mar;316(3):1098-106. doi: 10.1124/jpet.105.093393. Epub 2005 Nov 8.
46 Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.
47 NCI60 cancer cell line panel data and RNAi analysis help identify EAF2 as a modulator of simvastatin and lovastatin response in HCT-116 cells. PLoS One. 2011 Apr 4;6(4):e18306. doi: 10.1371/journal.pone.0018306.
48 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.