General Information of Drug Combination (ID: DCOGRNR)

Drug Combination Name
Busulfan FORMESTANE
Indication
Disease Entry Status REF
Minimally invasive lung adenocarcinoma Investigative [1]
Component Drugs Busulfan   DMXYJ9C FORMESTANE   DMWIDJK
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: NCI-H322M
Zero Interaction Potency (ZIP) Score: 4.67
Bliss Independence Score: 6.27
Loewe Additivity Score: 1.67
LHighest Single Agent (HSA) Score: 1.1

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Busulfan
Disease Entry ICD 11 Status REF
Chronic myelogenous leukaemia 2A20.0 Approved [2]
Hematologic disease 3C0Z Approved [2]
Immunodeficiency 4A00-4A85 Approved [2]
Leukemia N.A. Approved [2]
Myeloproliferative syndrome 2A22 Approved [3]
Systemic lupus erythematosus 4A40.0 Approved [2]
Systemic sclerosis 4A42 Approved [2]
Neuroblastoma 2D11.2 Investigative [2]
Retinoblastoma 2D02.2 Investigative [2]
Busulfan Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Modulator [6]
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Busulfan Interacts with 6 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [7]
Glutathione S-transferase alpha-1 (GSTA1) DE4ZHS1 GSTA1_HUMAN Metabolism [8]
Glutathione S-transferase alpha-2 (GSTA2) DEH49YS GSTA2_HUMAN Metabolism [9]
Glutathione S-transferase pi (GSTP1) DEK6079 GSTP1_HUMAN Metabolism [10]
Microsomal glutathione S-transferase 2 (MGST2) DE31KMQ MGST2_HUMAN Metabolism [11]
Glutathione S-transferase mu-1 (GSTM1) DEYZEJA GSTM1_HUMAN Metabolism [10]
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⏷ Show the Full List of 6 DME(s)
Busulfan Interacts with 34 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Glutathione S-transferase P (GSTP1) OTLP0A0Y GSTP1_HUMAN Affects Abundance [12]
Glutathione S-transferase Mu 1 (GSTM1) OTSBF2MO GSTM1_HUMAN Affects Abundance [12]
Microsomal glutathione S-transferase 2 (MGST2) OT4UGTDO MGST2_HUMAN Decreases Response To Substance [11]
Glutathione S-transferase A1 (GSTA1) OTA7K5XA GSTA1_HUMAN Decreases Response To Substance [13]
Serotransferrin (TF) OT41PEMS TRFE_HUMAN Increases Expression [14]
Inhibin beta A chain (INHBA) OTSP64PQ INHBA_HUMAN Increases Expression [14]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Increases Expression [14]
Antithrombin-III (SERPINC1) OTDFATG0 ANT3_HUMAN Affects Expression [15]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Increases Expression [16]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Expression [16]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [5]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Activity [17]
Plasminogen activator inhibitor 1 (SERPINE1) OTT0MPQ3 PAI1_HUMAN Increases Expression [16]
Thrombospondin-1 (THBS1) OT0ECWK3 TSP1_HUMAN Increases Expression [16]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [18]
Tissue factor pathway inhibitor (TFPI) OTA0FX16 TFPI1_HUMAN Decreases Expression [16]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Phosphorylation [18]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4) OTRFV19J ATF4_HUMAN Increases Expression [5]
Nuclear factor NF-kappa-B p105 subunit (NFKB1) OTNRRD8I NFKB1_HUMAN Increases Expression [5]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Activity [19]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Activity [19]
Aryl hydrocarbon receptor (AHR) OTFE4EYE AHR_HUMAN Increases Expression [5]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Affects Expression [5]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [19]
Signal transducer and activator of transcription 1-alpha/beta (STAT1) OTLMBUZ6 STAT1_HUMAN Affects Expression [5]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [20]
Signal transducer and activator of transcription 2 (STAT2) OTO9G2RZ STAT2_HUMAN Decreases Expression [5]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Activity [18]
Metal regulatory transcription factor 1 (MTF1) OTJWVLLF MTF1_HUMAN Decreases Expression [5]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Increases Expression [5]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Increases Expression [5]
Pseudouridylate synthase 7 homolog (PUS7) OTE5AQHJ PUS7_HUMAN Increases Expression [21]
DNA repair nuclease/redox regulator APEX1 (APEX1) OT53OI14 APEX1_HUMAN Increases Response To Substance [22]
Rho GDP-dissociation inhibitor 1 (ARHGDIA) OTEXWJDO GDIR1_HUMAN Affects Response To Substance [20]
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⏷ Show the Full List of 34 DOT(s)
Indication(s) of FORMESTANE
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Withdrawn from market [4]
FORMESTANE Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Aromatase (CYP19A1) TTSZLWK CP19A_HUMAN Inhibitor [23]
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FORMESTANE Interacts with 5 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Adenylate kinase isoenzyme 1 (AK1) OT614AR3 KAD1_HUMAN Increases ADR [24]
Aromatase (CYP19A1) OTZ6XF74 CP19A_HUMAN Decreases Activity [25]
17-beta-hydroxysteroid dehydrogenase type 1 (HSD17B1) OT6EBDHM DHB1_HUMAN Decreases Activity [26]
Estrogen receptor (ESR1) OTKLU61J ESR1_HUMAN Increases Expression [27]
Androgen receptor (AR) OTUBKAZZ ANDR_HUMAN Increases Expression [27]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adenocarcinoma DCAKJE8 OVCAR3 Investigative [1]
Adenocarcinoma DCKU2XL NCIH23 Investigative [1]
Adenocarcinoma DCA5UUM HCT116 Investigative [1]
Adenocarcinoma DCPZWMS SW-620 Investigative [1]
Adult acute myeloid leukemia DCV2S7Q HL-60(TB) Investigative [1]
Adult T acute lymphoblastic leukemia DC53DMC MOLT-4 Investigative [1]
Amelanotic melanoma DCG9EBX M14 Investigative [1]
Astrocytoma DC5BTNT SNB-19 Investigative [1]
Childhood T acute lymphoblastic leukemia DCIFTSN CCRF-CEM Investigative [1]
Chronic myelogenous leukemia DCL9ESH K-562 Investigative [1]
Clear cell renal cell carcinoma DC1ONGM TK-10 Investigative [1]
Cutaneous melanoma DCTBO2K SK-MEL-28 Investigative [1]
Cutaneous melanoma DCWSZ9N SK-MEL-5 Investigative [1]
Glioma DC9DVP6 SF-539 Investigative [1]
High grade ovarian serous adenocarcinoma DCG6N37 OVCAR-8 Investigative [1]
High grade ovarian serous adenocarcinoma DC304KY NCI\\/ADR-RES Investigative [1]
Lung adenocarcinoma DCU6VSB HOP-62 Investigative [1]
Melanoma DCPI0H0 SK-MEL-2 Investigative [1]
Pleural epithelioid mesothelioma DCQGM53 NCI-H226 Investigative [1]
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⏷ Show the Full List of 19 DrugCom(s)

References

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2 Busulfan FDA Label
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4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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8 Glutathione S-transferase M1 polymorphism: a risk factor for hepatic venoocclusive disease in bone marrow transplantation. Blood. 2004 Sep 1;104(5):1574-7.
9 Endothelial cells do not express GSTA1: potential relevance to busulfan-mediated endothelial damage during haematopoietic stem cell transplantation. Eur J Haematol. 2008 Apr;80(4):299-302.
10 Busulfan conjugation by glutathione S-transferases alpha, mu, and pi. Drug Metab Dispos. 1996 Sep;24(9):1015-9.
11 Overexpression of glutathione-S-transferase, MGSTII, confers resistance to busulfan and melphalan. Cancer Invest. 2005;23(1):19-25.
12 Influence of glutathione S-transferase A1, P1, M1, T1 polymorphisms on oral busulfan pharmacokinetics in children with congenital hemoglobinopathies undergoing hematopoietic stem cell transplantation. Pediatr Blood Cancer. 2010 Dec 1;55(6):1172-9. doi: 10.1002/pbc.22739.
13 Overexpression of glutathione S-transferase A1-1 in ECV 304 cells protects against busulfan mediated G2-arrest and induces tissue factor expression. Br J Pharmacol. 2002 Dec;137(7):1100-6. doi: 10.1038/sj.bjp.0704972.
14 Busulfan induces activin A expression in vitro and in vivo: a possible link to venous occlusive disease. Clin Pharmacol Ther. 2003 Sep;74(3):264-74.
15 Decreased incidence of hepatic veno-occlusive disease and fewer hemostatic derangements associated with intravenous busulfan vs oral busulfan in adults conditioned with busulfan + cyclophosphamide for allogeneic bone marrow transplantation. Ann Hematol. 2005 May;84(5):321-30. doi: 10.1007/s00277-004-0982-4. Epub 2004 Dec 4.
16 Antineoplastic agent busulfan regulates a network of genes related to coagulation and fibrinolysis. Eur J Clin Pharmacol. 2012 Jun;68(6):923-35. doi: 10.1007/s00228-011-1209-y.
17 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.
18 Altered gene expression in busulfan-resistant human myeloid leukemia. Leuk Res. 2008 Nov;32(11):1684-97. doi: 10.1016/j.leukres.2008.01.016. Epub 2008 Mar 12.
19 Busulfan selectively induces cellular senescence but not apoptosis in WI38 fibroblasts via a p53-independent but extracellular signal-regulated kinase-p38 mitogen-activated protein kinase-dependent mechanism. J Pharmacol Exp Ther. 2006 Nov;319(2):551-60. doi: 10.1124/jpet.106.107771. Epub 2006 Aug 1.
20 Reduced expression of Rho guanine nucleotide dissociation inhibitor-alpha modulates the cytotoxic effect of busulfan in HEK293 cells. Anticancer Drugs. 2007 Mar;18(3):333-40. doi: 10.1097/CAD.0b013e328011fd7f.
21 CD34+ derived macrophage and dendritic cells display differential responses to paraquat. Toxicol In Vitro. 2021 Sep;75:105198. doi: 10.1016/j.tiv.2021.105198. Epub 2021 Jun 9.
22 Impairment of APE1 function enhances cellular sensitivity to clinically relevant alkylators and antimetabolites. Mol Cancer Res. 2009 Jun;7(6):897-906. doi: 10.1158/1541-7786.MCR-08-0519. Epub 2009 May 26.
23 The taiwaniaquinoids: a review. J Nat Prod. 2010 Feb 26;73(2):284-98.
24 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.
25 Screening of selected pesticides for inhibition of CYP19 aromatase activity in vitro. Toxicol In Vitro. 2000 Jun;14(3):227-34.
26 Mammalian lignans and genistein decrease the activities of aromatase and 17beta-hydroxysteroid dehydrogenase in MCF-7 cells. J Steroid Biochem Mol Biol. 2005 Apr;94(5):461-7.
27 Androgen- and estrogen-receptor mediated activities of 4-hydroxytestosterone, 4-hydroxyandrostenedione and their human metabolites in yeast based assays. Toxicol Lett. 2018 Aug;292:39-45. doi: 10.1016/j.toxlet.2018.04.026. Epub 2018 Apr 24.