Details of the Drug Combination

General Information of Drug Combination (ID: DC68296)

Drug Combination Name
Acitretin PF-02545920
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Acitretin   DM8BKU9 PF-02545920   DMJPE61
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: 7.53
Bliss Independence Score: 7.53
Loewe Additivity Score: 27.04
LHighest Single Agent (HSA) Score: 27.05

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Acitretin
Disease Entry ICD 11 Status REF
Psoriasis vulgaris EA90 Approved [2]
Acitretin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Signal transducer and activator of transcription 3 (STAT3) TTH8FZW STAT3_HUMAN Inhibitor [5]
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Acitretin Interacts with 14 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Activity [6]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Activity [7]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [8]
Retinoic acid receptor RXR-alpha (RXRA) OTP1TBDM RXRA_HUMAN Affects Binding [9]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [10]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Increases Expression [7]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Expression [10]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Expression [10]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [11]
Tumor necrosis factor ligand superfamily member 6 (FASLG) OTZARCHH TNFL6_HUMAN Increases Expression [7]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Activity [7]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [8]
FAS-associated death domain protein (FADD) OTV7GFHH FADD_HUMAN Increases Expression [7]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Activity [7]
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⏷ Show the Full List of 14 DOT(s)
Indication(s) of PF-02545920
Disease Entry ICD 11 Status REF
Huntington disease 8A01.10 Phase 2 [3]
Schizophrenia 6A20 Phase 2 [4]
PF-02545920 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Phosphodiesterase 10A (PDE10) TTJW4LU PDE10_HUMAN Inhibitor [3]
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PF-02545920 Interacts with 3 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Lipid transferase CIDEA (CIDEA) OTDUTSOV CIDEA_HUMAN Increases Expression [12]
Type II iodothyronine deiodinase (DIO2) OTGPNSLH IOD2_HUMAN Increases Expression [12]
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) OTHCDQ22 PRGC1_HUMAN Increases Expression [12]
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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 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: 7598).
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 ClinicalTrials.gov (NCT01939548) An Outpatient Study Of The Efficacy, Safety, And Tolerability Of PF-02545920 In The Adjunctive Treatment Of Sub-Optimally Controlled Symptoms of Schizophrenia. U.S. National Institutes of Health.
5 Effects of acitretin on the expression of signaling pathway-related genes in epidermal squamous-cell carcinoma cells. Zhonghua Zhong Liu Za Zhi. 2006 Jan;28(1):21-4.
6 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.
7 Acitretin induces apoptosis through CD95 signalling pathway in human cutaneous squamous cell carcinoma cell line SCL-1. J Cell Mol Med. 2009 Sep;13(9A):2888-98. doi: 10.1111/j.1582-4934.2008.00397.x. Epub 2009 Jun 20.
8 [Effects of all-trans-retinoic acid, acitretin and tazarotene on apoptosis and Bax/Bcl-2 expressions of human melanoma cells A375 and the significance]. Di Yi Jun Yi Da Xue Xue Bao. 2005 Aug;25(8):972-4, 978.
9 Limited Chemical Structural Diversity Found to Modulate Thyroid Hormone Receptor in the Tox21 Chemical Library. Environ Health Perspect. 2019 Sep;127(9):97009. doi: 10.1289/EHP5314. Epub 2019 Sep 30.
10 [Acitretin induces apoptosis and changes of relative signaling pathway in epidermoid carcinoma cell line A431]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2006 Mar;35(2):182-8. doi: 10.3785/j.issn.1008-9292.2006.02.013.
11 Effects of ATRA, acitretin and tazarotene on growth and apoptosis of Tca8113 cells. J Huazhong Univ Sci Technolog Med Sci. 2005;25(4):393-6. doi: 10.1007/BF02828205.
12 A novel thermoregulatory role for PDE10A in mouse and human adipocytes. EMBO Mol Med. 2016 Jul 1;8(7):796-812. doi: 10.15252/emmm.201506085. Print 2016 Jul.