Details of the Drug Combination

General Information of Drug Combination (ID: DCPDJND)

Drug Combination Name
PF-05212384 Palbociclib
Indication
Disease Entry Status REF
Lung Cancer Squamous Cell Phase 1 [1]
Component Drugs PF-05212384   DMBL3VD Palbociclib   DMD7L94
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of PF-05212384
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 2 [2]
PF-05212384 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Serine/threonine-protein kinase mTOR (mTOR) TTCJG29 MTOR_HUMAN Modulator [6]
PI3-kinase gamma (PIK3CG) TTHBTOP PK3CG_HUMAN Modulator [6]
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Indication(s) of Palbociclib
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Approved [3]
Solid tumour/cancer 2A00-2F9Z Phase 2 [4]
Schizophrenia 6A20 Terminated [5]
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 [3]
Cyclin-dependent kinase 6 (CDK6) TTO0FDJ CDK6_HUMAN Modulator [3]
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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 [8]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [8]
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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 [9]
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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 [7]
Kinetochore protein NDC80 homolog (NDC80) OTS7D306 NDC80_HUMAN Decreases Expression [7]
Monocarboxylate transporter 5 (SLC16A4) OT1YXBKC MOT5_HUMAN Increases Expression [7]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [7]
Protein Mis18-beta (OIP5) OTI5C2DE MS18B_HUMAN Decreases Expression [7]
Zinc finger protein SNAI2 (SNAI2) OT7Y8EJ2 SNAI2_HUMAN Increases Expression [7]
Protein regulator of cytokinesis 1 (PRC1) OTHD0XS0 PRC1_HUMAN Decreases Expression [7]
Mitotic checkpoint serine/threonine-protein kinase BUB1 (BUB1) OT80DZMT BUB1_HUMAN Decreases Expression [7]
Hyaluronan mediated motility receptor (HMMR) OT4M0JTZ HMMR_HUMAN Decreases Expression [7]
Cell division control protein 45 homolog (CDC45) OT6NNLOD CDC45_HUMAN Decreases Expression [7]
Glutaminase kidney isoform, mitochondrial (GLS) OTGOZG2M GLSK_HUMAN Increases Expression [10]
G2/mitotic-specific cyclin-B2 (CCNB2) OTIEXTDK CCNB2_HUMAN Decreases Expression [7]
Serine protease 23 (PRSS23) OT6DQAM1 PRS23_HUMAN Increases Expression [7]
Kinesin-like protein KIF20A (KIF20A) OTXOQHE0 KI20A_HUMAN Decreases Expression [7]
Chromosome-associated kinesin KIF4A (KIF4A) OT3UWL7D KIF4A_HUMAN Decreases Expression [7]
Phospholipid-transporting ATPase ABCA1 (ABCA1) OT94G6BQ ABCA1_HUMAN Increases Expression [7]
Securin (PTTG1) OTIMYS4W PTTG1_HUMAN Decreases Expression [7]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Decreases Expression [11]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Increases Activity [7]
Thymidine kinase, cytosolic (TK1) OTY5JFM1 KITH_HUMAN Decreases Expression [12]
Plasminogen activator inhibitor 1 (SERPINE1) OTT0MPQ3 PAI1_HUMAN Increases Expression [7]
SPARC (SPARC) OTPN90H0 SPRC_HUMAN Increases Expression [10]
Cadherin-1 (CDH1) OTFJMXPM CADH1_HUMAN Affects Localization [7]
Elastin (ELN) OTFSO7PG ELN_HUMAN Increases Expression [13]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Decreases Phosphorylation [14]
Cadherin-2 (CDH2) OTH0Y56P CADH2_HUMAN Increases Expression [7]
Lamin-B1 (LMNB1) OT100T3P LMNB1_HUMAN Decreases Expression [7]
Ribonucleoside-diphosphate reductase large subunit (RRM1) OTXGQOR9 RIR1_HUMAN Decreases Expression [7]
Retinoblastoma-like protein 1 (RBL1) OTDEBFYC RBL1_HUMAN Decreases Expression [15]
G1/S-specific cyclin-D3 (CCND3) OTNKPQ22 CCND3_HUMAN Increases Expression [16]
M-phase inducer phosphatase 1 (CDC25A) OTSLKKCO MPIP1_HUMAN Decreases Expression [7]
M-phase inducer phosphatase 3 (CDC25C) OTPQI71S MPIP3_HUMAN Decreases Expression [7]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Increases Expression [7]
Receptor-type tyrosine-protein kinase FLT3 (FLT3) OTMSRYMK FLT3_HUMAN Decreases Expression [11]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [16]
Flap endonuclease 1 (FEN1) OT6QGG7O FEN1_HUMAN Decreases Expression [7]
Replication factor C subunit 5 (RFC5) OTAD79RT RFC5_HUMAN Decreases Expression [7]
Cyclin-F (CCNF) OTJFVU43 CCNF_HUMAN Decreases Expression [7]
Lamina-associated polypeptide 2, isoform alpha (TMPO) OTL68EL4 LAP2A_HUMAN Decreases Expression [7]
Ran-specific GTPase-activating protein (RANBP1) OTQE226K RANG_HUMAN Decreases Expression [10]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Increases Expression [17]
Histone H3-like centromeric protein A (CENPA) OT0NEJ4X CENPA_HUMAN Decreases Expression [7]
Centromere protein F (CENPF) OT7AG0SW CENPF_HUMAN Decreases Expression [7]
DNA primase small subunit (PRIM1) OTWWP8Y6 PRI1_HUMAN Decreases Expression [7]
Serine/threonine-protein kinase Nek2 (NEK2) OT1H27HO NEK2_HUMAN Decreases Expression [7]
Importin subunit alpha-1 (KPNA2) OTU7FOE6 IMA1_HUMAN Decreases Expression [7]
Serine/threonine-protein kinase PLK1 (PLK1) OTRZX45T PLK1_HUMAN Decreases Expression [7]
DNA polymerase epsilon subunit 2 (POLE2) OTAC9V6L DPOE2_HUMAN Decreases Expression [7]
Small ribosomal subunit protein uS14 (RPS29) OTCC1872 RS29_HUMAN Increases Expression [7]
Histone H4 (H4C1) OTB71W46 H4_HUMAN Decreases Expression [7]
G-protein-signaling modulator 2 (GPSM2) OT6RPMRM GPSM2_HUMAN Decreases Expression [7]
Centromere-associated protein E (CENPE) OTQ7AP04 CENPE_HUMAN Decreases Expression [7]
Kinesin-like protein KIF23 (KIF23) OTY850JC KIF23_HUMAN Decreases Expression [7]
Retinoblastoma-like protein 2 (RBL2) OTBQSOE6 RBL2_HUMAN Decreases Phosphorylation [18]
Tastin (TROAP) OTC8CE0R TROAP_HUMAN Decreases Expression [7]
Laminin subunit beta-3 (LAMB3) OTFPU6W8 LAMB3_HUMAN Increases Expression [7]
Laminin subunit gamma-2 (LAMC2) OTJMTM72 LAMC2_HUMAN Increases Expression [7]
DNA polymerase alpha subunit B (POLA2) OTTWQ73N DPOA2_HUMAN Decreases Expression [7]
Max dimerization protein 4 (MXD4) OTUCXFRO MAD4_HUMAN Increases Expression [7]
PCNA-associated factor (PCLAF) OTMVIOUU PAF15_HUMAN Decreases Expression [7]
Condensin complex subunit 1 (NCAPD2) OT8VGE2O CND1_HUMAN Decreases Expression [7]
Kinesin-like protein KIF14 (KIF14) OTXHT4JM KIF14_HUMAN Decreases Expression [7]
Disks large-associated protein 5 (DLGAP5) OTWCN39U DLGP5_HUMAN Decreases Expression [7]
SCL-interrupting locus protein (STIL) OT9799VN STIL_HUMAN Decreases Expression [7]
Cyclin-dependent kinase inhibitor 3 (CDKN3) OTBE3H07 CDKN3_HUMAN Decreases Expression [7]
Laminin subunit alpha-3 (LAMA3) OTFME7HT LAMA3_HUMAN Increases Expression [7]
Centrosomal protein of 55 kDa (CEP55) OTGSG2PA CEP55_HUMAN Decreases Expression [7]
PHD finger protein 19 (PHF19) OTF6RUCR PHF19_HUMAN Decreases Expression [7]
Proline/serine-rich coiled-coil protein 1 (PSRC1) OT7MDJMN PSRC1_HUMAN Decreases Expression [7]
Protein aurora borealis (BORA) OTV2ZPKP BORA_HUMAN Decreases Expression [7]
Interleukin-20 receptor subunit beta (IL20RB) OTHFXK95 I20RB_HUMAN Increases Expression [7]
Protein MCM10 homolog (MCM10) OTV0O3JN MCM10_HUMAN Decreases Expression [7]
Suppressor APC domain-containing protein 2 (SAPCD2) OTXS0EXM SAPC2_HUMAN Decreases Expression [7]
Condensin-2 complex subunit G2 (NCAPG2) OTZYENKO CNDG2_HUMAN Decreases Expression [7]
Cytoskeleton-associated protein 2-like (CKAP2L) OT4T73GG CKP2L_HUMAN Decreases Expression [7]
Kinetochore protein Spc24 (SPC24) OT1HVYV4 SPC24_HUMAN Decreases Expression [7]
Holliday junction recognition protein (HJURP) OTWMV16B HJURP_HUMAN Decreases Expression [7]
Protein DENND6B (DENND6B) OTZ006UD DEN6B_HUMAN Increases Expression [7]
DEP domain-containing protein 1B (DEPDC1B) OTMVFOT1 DEP1B_HUMAN Decreases Expression [7]
RAD51-associated protein 1 (RAD51AP1) OTXM7UTD R51A1_HUMAN Decreases Expression [7]
Sororin (CDCA5) OTZLCQ5U CDCA5_HUMAN Decreases Expression [7]
Proline-rich protein 11 (PRR11) OT2JJ08Z PRR11_HUMAN Decreases Expression [7]
Lymphokine-activated killer T-cell-originated protein kinase (PBK) OT5Z27TW TOPK_HUMAN Decreases Expression [7]
Tetratricopeptide repeat protein 14 (TTC14) OTMTYOPF TTC14_HUMAN Increases Expression [7]
Serine protease FAM111A (FAM111A) OTVLARLG F111A_HUMAN Decreases Expression [7]
Cell division cycle-associated protein 3 (CDCA3) OTUI8QK3 CDCA3_HUMAN Decreases Expression [7]
Kinesin-like protein KIF2C (KIF2C) OTJ8G3NP KIF2C_HUMAN Decreases Expression [7]
BRCA1-associated RING domain protein 1 (BARD1) OTTC0Z9Y BARD1_HUMAN Decreases Expression [7]
Condensin complex subunit 3 (NCAPG) OT1AI9EO CND3_HUMAN Decreases Expression [7]
Protein PIMREG (PIMREG) OTKC8T3E PIMRE_HUMAN Decreases Expression [7]
Kinesin-like protein KIFC1 (KIFC1) OTNQDS00 KIFC1_HUMAN Decreases Expression [7]
Nucleolar and spindle-associated protein 1 (NUSAP1) OT85HIJ5 NUSAP_HUMAN Decreases Expression [7]
Rac GTPase-activating protein 1 (RACGAP1) OTQE8IEH RGAP1_HUMAN Decreases Expression [7]
DNA replication factor Cdt1 (CDT1) OTVY53VG CDT1_HUMAN Decreases Expression [7]
Protein FAM83D (FAM83D) OTQWZ1UO FA83D_HUMAN Decreases Expression [7]
Fanconi anemia group E protein (FANCE) OTKRPBW1 FANCE_HUMAN Decreases Expression [10]
Kinetochore protein Spc25 (SPC25) OTCAS0OH SPC25_HUMAN Decreases Expression [7]
Inner centromere protein (INCENP) OT9HFRYK INCE_HUMAN Decreases Expression [7]
Anillin (ANLN) OTXJY54C ANLN_HUMAN Decreases Expression [7]
Kinesin-like protein KIF15 (KIF15) OTJRJEXL KIF15_HUMAN Decreases Expression [7]
Centromere protein M (CENPM) OTYK9KOX CENPM_HUMAN Decreases Expression [7]
Structural maintenance of chromosomes protein 4 (SMC4) OTEJE6AG SMC4_HUMAN Decreases Expression [7]
Fanconi anemia group I protein (FANCI) OTW8E3SC FANCI_HUMAN Decreases Expression [7]
Histone chaperone ASF1B (ASF1B) OTKXX12I ASF1B_HUMAN Decreases Expression [7]
Protein downstream neighbor of Son (DONSON) OTN5HE0W DONS_HUMAN Decreases Expression [7]
F-box only protein 5 (FBXO5) OTTR957W FBX5_HUMAN Decreases Expression [7]
Targeting protein for Xklp2 (TPX2) OTWLJYH0 TPX2_HUMAN Decreases Expression [7]
Exonuclease 1 (EXO1) OTI87RS5 EXO1_HUMAN Decreases Expression [7]
DNA replication complex GINS protein PSF2 (GINS2) OT974IYI PSF2_HUMAN Decreases Expression [7]
Small kinetochore-associated protein (KNSTRN) OTYA7UXS SKAP_HUMAN Decreases Expression [7]
Transforming acidic coiled-coil-containing protein 3 (TACC3) OTRNEZTA TACC3_HUMAN Decreases Expression [10]
Cyclin-dependent kinase 4 inhibitor B (CDKN2B) OTAG24N1 CDN2B_HUMAN Decreases Response To Substance [19]
Cyclin-dependent kinase inhibitor 2A (CDKN2A) OTN0ZWAE CDN2A_HUMAN Increases Response To Substance [20]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Response To Substance [20]
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⏷ Show the Full List of 114 DOT(s)

References

1 ClinicalTrials.gov (NCT03065062) Study of the CDK4/6 Inhibitor Palbociclib (PD-0332991) in Combination With the PI3K/mTOR Inhibitor Gedatolisib (PF-05212384) for Patients With Advanced Squamous Cell Lung, Pancreatic, Head & Neck and Other Solid Tumors
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: 7940).
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2017
4 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.
5 The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
6 First-in-Human Study of PF-05212384 (PKI-587), a Small-Molecule, Intravenous, Dual Inhibitor of PI3K and mTOR in Patients with Advanced Cancer. Clin Cancer Res. 2015 Apr 15;21(8):1888-95.
7 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.
8 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.
9 Progress with palbociclib in breast cancer: latest evidence and clinical considerations. Ther Adv Med Oncol. 2017 Feb;9(2):83-105.
10 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.
11 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.
12 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.
13 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.
14 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.
15 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.
16 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.
17 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.
18 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.
19 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.
20 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.