Details of the Drug Combination

General Information of Drug Combination (ID: DCIFUAV)

Drug Combination Name
Palbociclib PHA848125
Indication
Disease Entry Status REF
Diffuse intrinsic pontine glioma Investigative [1]
Component Drugs Palbociclib   DMD7L94 PHA848125   DMS2Q9G
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: DIPG25
Zero Interaction Potency (ZIP) Score: 14.016
Bliss Independence Score: 14.757
Loewe Additivity Score: 9.997
LHighest Single Agent (HSA) Score: 13.007

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Palbociclib
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Approved [2]
Solid tumour/cancer 2A00-2F9Z Phase 2 [3]
Schizophrenia 6A20 Terminated [4]
Palbociclib Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Cyclin-dependent kinase 4 (CDK4) TT0PG8F CDK4_HUMAN Modulator [2]
Cyclin-dependent kinase 6 (CDK6) TTO0FDJ CDK6_HUMAN Modulator [2]
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Palbociclib Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [7]
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Palbociclib Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [8]
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Palbociclib Interacts with 114 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
CCN family member 1 (CCN1) OTKJBEMD CCN1_HUMAN Increases Expression [6]
Kinetochore protein NDC80 homolog (NDC80) OTS7D306 NDC80_HUMAN Decreases Expression [6]
Monocarboxylate transporter 5 (SLC16A4) OT1YXBKC MOT5_HUMAN Increases Expression [6]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [6]
Protein Mis18-beta (OIP5) OTI5C2DE MS18B_HUMAN Decreases Expression [6]
Zinc finger protein SNAI2 (SNAI2) OT7Y8EJ2 SNAI2_HUMAN Increases Expression [6]
Protein regulator of cytokinesis 1 (PRC1) OTHD0XS0 PRC1_HUMAN Decreases Expression [6]
Mitotic checkpoint serine/threonine-protein kinase BUB1 (BUB1) OT80DZMT BUB1_HUMAN Decreases Expression [6]
Hyaluronan mediated motility receptor (HMMR) OT4M0JTZ HMMR_HUMAN Decreases Expression [6]
Cell division control protein 45 homolog (CDC45) OT6NNLOD CDC45_HUMAN Decreases Expression [6]
Glutaminase kidney isoform, mitochondrial (GLS) OTGOZG2M GLSK_HUMAN Increases Expression [9]
G2/mitotic-specific cyclin-B2 (CCNB2) OTIEXTDK CCNB2_HUMAN Decreases Expression [6]
Serine protease 23 (PRSS23) OT6DQAM1 PRS23_HUMAN Increases Expression [6]
Kinesin-like protein KIF20A (KIF20A) OTXOQHE0 KI20A_HUMAN Decreases Expression [6]
Chromosome-associated kinesin KIF4A (KIF4A) OT3UWL7D KIF4A_HUMAN Decreases Expression [6]
Phospholipid-transporting ATPase ABCA1 (ABCA1) OT94G6BQ ABCA1_HUMAN Increases Expression [6]
Securin (PTTG1) OTIMYS4W PTTG1_HUMAN Decreases Expression [6]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Decreases Expression [10]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Increases Activity [6]
Thymidine kinase, cytosolic (TK1) OTY5JFM1 KITH_HUMAN Decreases Expression [11]
Plasminogen activator inhibitor 1 (SERPINE1) OTT0MPQ3 PAI1_HUMAN Increases Expression [6]
SPARC (SPARC) OTPN90H0 SPRC_HUMAN Increases Expression [9]
Cadherin-1 (CDH1) OTFJMXPM CADH1_HUMAN Affects Localization [6]
Elastin (ELN) OTFSO7PG ELN_HUMAN Increases Expression [12]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Decreases Phosphorylation [13]
Cadherin-2 (CDH2) OTH0Y56P CADH2_HUMAN Increases Expression [6]
Lamin-B1 (LMNB1) OT100T3P LMNB1_HUMAN Decreases Expression [6]
Ribonucleoside-diphosphate reductase large subunit (RRM1) OTXGQOR9 RIR1_HUMAN Decreases Expression [6]
Retinoblastoma-like protein 1 (RBL1) OTDEBFYC RBL1_HUMAN Decreases Expression [14]
G1/S-specific cyclin-D3 (CCND3) OTNKPQ22 CCND3_HUMAN Increases Expression [15]
M-phase inducer phosphatase 1 (CDC25A) OTSLKKCO MPIP1_HUMAN Decreases Expression [6]
M-phase inducer phosphatase 3 (CDC25C) OTPQI71S MPIP3_HUMAN Decreases Expression [6]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Increases Expression [6]
Receptor-type tyrosine-protein kinase FLT3 (FLT3) OTMSRYMK FLT3_HUMAN Decreases Expression [10]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [15]
Flap endonuclease 1 (FEN1) OT6QGG7O FEN1_HUMAN Decreases Expression [6]
Replication factor C subunit 5 (RFC5) OTAD79RT RFC5_HUMAN Decreases Expression [6]
Cyclin-F (CCNF) OTJFVU43 CCNF_HUMAN Decreases Expression [6]
Lamina-associated polypeptide 2, isoform alpha (TMPO) OTL68EL4 LAP2A_HUMAN Decreases Expression [6]
Ran-specific GTPase-activating protein (RANBP1) OTQE226K RANG_HUMAN Decreases Expression [9]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Increases Expression [16]
Histone H3-like centromeric protein A (CENPA) OT0NEJ4X CENPA_HUMAN Decreases Expression [6]
Centromere protein F (CENPF) OT7AG0SW CENPF_HUMAN Decreases Expression [6]
DNA primase small subunit (PRIM1) OTWWP8Y6 PRI1_HUMAN Decreases Expression [6]
Serine/threonine-protein kinase Nek2 (NEK2) OT1H27HO NEK2_HUMAN Decreases Expression [6]
Importin subunit alpha-1 (KPNA2) OTU7FOE6 IMA1_HUMAN Decreases Expression [6]
Serine/threonine-protein kinase PLK1 (PLK1) OTRZX45T PLK1_HUMAN Decreases Expression [6]
DNA polymerase epsilon subunit 2 (POLE2) OTAC9V6L DPOE2_HUMAN Decreases Expression [6]
Small ribosomal subunit protein uS14 (RPS29) OTCC1872 RS29_HUMAN Increases Expression [6]
Histone H4 (H4C1) OTB71W46 H4_HUMAN Decreases Expression [6]
G-protein-signaling modulator 2 (GPSM2) OT6RPMRM GPSM2_HUMAN Decreases Expression [6]
Centromere-associated protein E (CENPE) OTQ7AP04 CENPE_HUMAN Decreases Expression [6]
Kinesin-like protein KIF23 (KIF23) OTY850JC KIF23_HUMAN Decreases Expression [6]
Retinoblastoma-like protein 2 (RBL2) OTBQSOE6 RBL2_HUMAN Decreases Phosphorylation [17]
Tastin (TROAP) OTC8CE0R TROAP_HUMAN Decreases Expression [6]
Laminin subunit beta-3 (LAMB3) OTFPU6W8 LAMB3_HUMAN Increases Expression [6]
Laminin subunit gamma-2 (LAMC2) OTJMTM72 LAMC2_HUMAN Increases Expression [6]
DNA polymerase alpha subunit B (POLA2) OTTWQ73N DPOA2_HUMAN Decreases Expression [6]
Max dimerization protein 4 (MXD4) OTUCXFRO MAD4_HUMAN Increases Expression [6]
PCNA-associated factor (PCLAF) OTMVIOUU PAF15_HUMAN Decreases Expression [6]
Condensin complex subunit 1 (NCAPD2) OT8VGE2O CND1_HUMAN Decreases Expression [6]
Kinesin-like protein KIF14 (KIF14) OTXHT4JM KIF14_HUMAN Decreases Expression [6]
Disks large-associated protein 5 (DLGAP5) OTWCN39U DLGP5_HUMAN Decreases Expression [6]
SCL-interrupting locus protein (STIL) OT9799VN STIL_HUMAN Decreases Expression [6]
Cyclin-dependent kinase inhibitor 3 (CDKN3) OTBE3H07 CDKN3_HUMAN Decreases Expression [6]
Laminin subunit alpha-3 (LAMA3) OTFME7HT LAMA3_HUMAN Increases Expression [6]
Centrosomal protein of 55 kDa (CEP55) OTGSG2PA CEP55_HUMAN Decreases Expression [6]
PHD finger protein 19 (PHF19) OTF6RUCR PHF19_HUMAN Decreases Expression [6]
Proline/serine-rich coiled-coil protein 1 (PSRC1) OT7MDJMN PSRC1_HUMAN Decreases Expression [6]
Protein aurora borealis (BORA) OTV2ZPKP BORA_HUMAN Decreases Expression [6]
Interleukin-20 receptor subunit beta (IL20RB) OTHFXK95 I20RB_HUMAN Increases Expression [6]
Protein MCM10 homolog (MCM10) OTV0O3JN MCM10_HUMAN Decreases Expression [6]
Suppressor APC domain-containing protein 2 (SAPCD2) OTXS0EXM SAPC2_HUMAN Decreases Expression [6]
Condensin-2 complex subunit G2 (NCAPG2) OTZYENKO CNDG2_HUMAN Decreases Expression [6]
Cytoskeleton-associated protein 2-like (CKAP2L) OT4T73GG CKP2L_HUMAN Decreases Expression [6]
Kinetochore protein Spc24 (SPC24) OT1HVYV4 SPC24_HUMAN Decreases Expression [6]
Holliday junction recognition protein (HJURP) OTWMV16B HJURP_HUMAN Decreases Expression [6]
Protein DENND6B (DENND6B) OTZ006UD DEN6B_HUMAN Increases Expression [6]
DEP domain-containing protein 1B (DEPDC1B) OTMVFOT1 DEP1B_HUMAN Decreases Expression [6]
RAD51-associated protein 1 (RAD51AP1) OTXM7UTD R51A1_HUMAN Decreases Expression [6]
Sororin (CDCA5) OTZLCQ5U CDCA5_HUMAN Decreases Expression [6]
Proline-rich protein 11 (PRR11) OT2JJ08Z PRR11_HUMAN Decreases Expression [6]
Lymphokine-activated killer T-cell-originated protein kinase (PBK) OT5Z27TW TOPK_HUMAN Decreases Expression [6]
Tetratricopeptide repeat protein 14 (TTC14) OTMTYOPF TTC14_HUMAN Increases Expression [6]
Serine protease FAM111A (FAM111A) OTVLARLG F111A_HUMAN Decreases Expression [6]
Cell division cycle-associated protein 3 (CDCA3) OTUI8QK3 CDCA3_HUMAN Decreases Expression [6]
Kinesin-like protein KIF2C (KIF2C) OTJ8G3NP KIF2C_HUMAN Decreases Expression [6]
BRCA1-associated RING domain protein 1 (BARD1) OTTC0Z9Y BARD1_HUMAN Decreases Expression [6]
Condensin complex subunit 3 (NCAPG) OT1AI9EO CND3_HUMAN Decreases Expression [6]
Protein PIMREG (PIMREG) OTKC8T3E PIMRE_HUMAN Decreases Expression [6]
Kinesin-like protein KIFC1 (KIFC1) OTNQDS00 KIFC1_HUMAN Decreases Expression [6]
Nucleolar and spindle-associated protein 1 (NUSAP1) OT85HIJ5 NUSAP_HUMAN Decreases Expression [6]
Rac GTPase-activating protein 1 (RACGAP1) OTQE8IEH RGAP1_HUMAN Decreases Expression [6]
DNA replication factor Cdt1 (CDT1) OTVY53VG CDT1_HUMAN Decreases Expression [6]
Protein FAM83D (FAM83D) OTQWZ1UO FA83D_HUMAN Decreases Expression [6]
Fanconi anemia group E protein (FANCE) OTKRPBW1 FANCE_HUMAN Decreases Expression [9]
Kinetochore protein Spc25 (SPC25) OTCAS0OH SPC25_HUMAN Decreases Expression [6]
Inner centromere protein (INCENP) OT9HFRYK INCE_HUMAN Decreases Expression [6]
Anillin (ANLN) OTXJY54C ANLN_HUMAN Decreases Expression [6]
Kinesin-like protein KIF15 (KIF15) OTJRJEXL KIF15_HUMAN Decreases Expression [6]
Centromere protein M (CENPM) OTYK9KOX CENPM_HUMAN Decreases Expression [6]
Structural maintenance of chromosomes protein 4 (SMC4) OTEJE6AG SMC4_HUMAN Decreases Expression [6]
Fanconi anemia group I protein (FANCI) OTW8E3SC FANCI_HUMAN Decreases Expression [6]
Histone chaperone ASF1B (ASF1B) OTKXX12I ASF1B_HUMAN Decreases Expression [6]
Protein downstream neighbor of Son (DONSON) OTN5HE0W DONS_HUMAN Decreases Expression [6]
F-box only protein 5 (FBXO5) OTTR957W FBX5_HUMAN Decreases Expression [6]
Targeting protein for Xklp2 (TPX2) OTWLJYH0 TPX2_HUMAN Decreases Expression [6]
Exonuclease 1 (EXO1) OTI87RS5 EXO1_HUMAN Decreases Expression [6]
DNA replication complex GINS protein PSF2 (GINS2) OT974IYI PSF2_HUMAN Decreases Expression [6]
Small kinetochore-associated protein (KNSTRN) OTYA7UXS SKAP_HUMAN Decreases Expression [6]
Transforming acidic coiled-coil-containing protein 3 (TACC3) OTRNEZTA TACC3_HUMAN Decreases Expression [9]
Cyclin-dependent kinase 4 inhibitor B (CDKN2B) OTAG24N1 CDN2B_HUMAN Decreases Response To Substance [18]
Cyclin-dependent kinase inhibitor 2A (CDKN2A) OTN0ZWAE CDN2A_HUMAN Increases Response To Substance [19]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Response To Substance [19]
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⏷ Show the Full List of 114 DOT(s)
Indication(s) of PHA848125
Disease Entry ICD 11 Status REF
Thymic cancer 2C27 Phase 2 [5]
PHA848125 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Cyclin-dependent kinase 2 (CDK2) TT7HF4W CDK2_HUMAN Inhibitor [20]
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References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2017
3 ClinicalTrials.gov (NCT01723774) PD 0332991 and Anastrozole for Stage 2 or 3 Estrogen Receptor Positive and HER2 Negative Breast Cancer. U.S. National Institutes of Health.
4 The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
5 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: 7938).
6 Cdk4/6 inhibition induces epithelial-mesenchymal transition and enhances invasiveness in pancreatic cancer cells. Mol Cancer Ther. 2012 Oct;11(10):2138-48. doi: 10.1158/1535-7163.MCT-12-0562. Epub 2012 Aug 6.
7 Efflux transporters at the blood-brain barrier limit delivery and efficacy of cyclin-dependent kinase 4/6 inhibitor palbociclib (PD-0332991) in an orthotopic brain tumor model. J Pharmacol Exp Ther. 2015 Nov;355(2):264-71.
8 Progress with palbociclib in breast cancer: latest evidence and clinical considerations. Ther Adv Med Oncol. 2017 Feb;9(2):83-105.
9 Biological specificity of CDK4/6 inhibitors: dose response relationship, in vivo signaling, and composite response signature. Oncotarget. 2017 Jul 4;8(27):43678-43691. doi: 10.18632/oncotarget.18435.
10 Palbociclib treatment of FLT3-ITD+ AML cells uncovers a kinase-dependent transcriptional regulation of FLT3 and PIM1 by CDK6. Blood. 2016 Jun 9;127(23):2890-902. doi: 10.1182/blood-2015-11-683581. Epub 2016 Apr 20.
11 Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther. 2004 Nov;3(11):1427-38.
12 Retinoblastoma protein modulates the inverse relationship between cellular proliferation and elastogenesis. J Biol Chem. 2011 Oct 21;286(42):36580-91. doi: 10.1074/jbc.M111.269944. Epub 2011 Aug 31.
13 CDK4/6 inhibition antagonizes the cytotoxic response to anthracycline therapy. Cell Cycle. 2012 Jul 15;11(14):2747-55. doi: 10.4161/cc.21127. Epub 2012 Jul 15.
14 Proliferative suppression by CDK4/6 inhibition: complex function of the retinoblastoma pathway in liver tissue and hepatoma cells. Gastroenterology. 2010 May;138(5):1920-30. doi: 10.1053/j.gastro.2010.01.007. Epub 2010 Jan 25.
15 Therapeutic CDK4/6 inhibition in breast cancer: key mechanisms of response and failure. Oncogene. 2010 Jul 15;29(28):4018-32. doi: 10.1038/onc.2010.154. Epub 2010 May 17.
16 Pharmacologic inhibition of CDK4/6: mechanistic evidence for selective activity or acquired resistance in acute myeloid leukemia. Blood. 2007 Sep 15;110(6):2075-83. doi: 10.1182/blood-2007-02-071266. Epub 2007 May 30.
17 Dual inhibition of CDK4/Rb and PI3K/AKT/mTOR pathways by ON123300 induces synthetic lethality in mantle cell lymphomas. Leukemia. 2016 Jan;30(1):86-93. doi: 10.1038/leu.2015.185. Epub 2015 Jul 15.
18 p16-Cdk4-Rb axis controls sensitivity to a cyclin-dependent kinase inhibitor PD0332991 in glioblastoma xenograft cells. Neuro Oncol. 2012 Jul;14(7):870-81. doi: 10.1093/neuonc/nos114. Epub 2012 Jun 18.
19 Expression of p16 and retinoblastoma determines response to CDK4/6 inhibition in ovarian cancer. Clin Cancer Res. 2011 Mar 15;17(6):1591-602. doi: 10.1158/1078-0432.CCR-10-2307. Epub 2011 Jan 28.
20 Identification of N,1,4,4-tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (PHA-848125), a potent, orally available cyclin dependent kinase inhibitor. J Med Chem. 2009 Aug 27;52(16):5152-63.