Details of the Drug Combination

General Information of Drug Combination (ID: DCIAJWJ)

Drug Combination Name
GDC0941 Obatoclax
Indication
Disease Entry Status REF
Glioblastoma Investigative [1]
Component Drugs GDC0941   DM1YAK6 Obatoclax   DMPF9ZM
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: JHH-136
Zero Interaction Potency (ZIP) Score: 83.434
Bliss Independence Score: 81.607
Loewe Additivity Score: 9.75
LHighest Single Agent (HSA) Score: 14.643

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of GDC0941
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Phase 2 [2]
Non-hodgkin lymphoma 2B33.5 Phase 2 [3]
Solid tumour/cancer 2A00-2F9Z Phase 2 [3]
GDC0941 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
PI3-kinase gamma (PIK3CG) TTHBTOP PK3CG_HUMAN Inhibitor [6]
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GDC0941 Interacts with 54 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [7]
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (PIK3CD) OTOMP6TH PK3CD_HUMAN Decreases Activity [8]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Increases Expression [9]
Forkhead box protein O3 (FOXO3) OTHXQG4P FOXO3_HUMAN Decreases Phosphorylation [10]
L-lactate dehydrogenase A chain (LDHA) OTN7K4XB LDHA_HUMAN Decreases Expression [11]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Decreases Expression [10]
High affinity nerve growth factor receptor (NTRK1) OTJORQAU NTRK1_HUMAN Decreases Activity [8]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [12]
Cyclin-dependent kinase 1 (CDK1) OTW1SC2N CDK1_HUMAN Decreases Phosphorylation [13]
Cathepsin B (CTSB) OTP9G5QB CATB_HUMAN Increases Expression [14]
Hepatocyte growth factor receptor (MET) OT7K55MU MET_HUMAN Increases Expression [5]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [15]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [12]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1) OTA675TJ GTR1_HUMAN Decreases Expression [11]
Lysosome-associated membrane glycoprotein 1 (LAMP1) OTYE92QY LAMP1_HUMAN Increases Expression [14]
G2/mitotic-specific cyclin-B1 (CCNB1) OT19S7E5 CCNB1_HUMAN Decreases Expression [13]
Transcription factor EB (TFEB) OTJUJJQY TFEB_HUMAN Increases Expression [14]
Receptor tyrosine-protein kinase erbB-3 (ERBB3) OTRSST0A ERBB3_HUMAN Increases Expression [5]
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Decreases Phosphorylation [16]
Eukaryotic translation initiation factor 4B (EIF4B) OTE8TXA8 IF4B_HUMAN Decreases Phosphorylation [12]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [13]
G1/S-specific cyclin-E1 (CCNE1) OTLD7UID CCNE1_HUMAN Decreases Expression [12]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Activity [17]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Activity [17]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [8]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [12]
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB) OTO8JQJA PK3CB_HUMAN Affects Activity [8]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Decreases Activity [18]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [19]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Increases Expression [12]
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (PIK3CG) OT3FAU4Y PK3CG_HUMAN Affects Activity [8]
Glycogen synthase kinase-3 beta (GSK3B) OTL3L14B GSK3B_HUMAN Decreases Phosphorylation [16]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [10]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [15]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [5]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) OTHBQVD5 4EBP1_HUMAN Decreases Phosphorylation [20]
Cyclin-G2 (CCNG2) OTII38K2 CCNG2_HUMAN Increases Expression [5]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Decreases Expression [11]
Carbonic anhydrase 9 (CA9) OTNA51XT CAH9_HUMAN Decreases Expression [11]
Atos homolog protein A (ATOSA) OTWFM5G0 ATOSA_HUMAN Increases Expression [5]
Bcl2-associated agonist of cell death (BAD) OT63ERYM BAD_HUMAN Decreases Phosphorylation [20]
Proline-rich AKT1 substrate 1 (AKT1S1) OT4JHN4Y AKTS1_HUMAN Decreases Phosphorylation [21]
Serine/threonine-protein kinase Sgk3 (SGK3) OTQ6QO99 SGK3_HUMAN Decreases Phosphorylation [13]
Phosphoinositide-3-kinase-interacting protein 1 (PIK3IP1) OTWE5G4T P3IP1_HUMAN Increases Expression [5]
UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase 110 kDa subunit (OGT) OT1Z1ZXE OGT1_HUMAN Increases Response To Substance [22]
RNA cytidine acetyltransferase (NAT10) OT6JQO26 NAT10_HUMAN Affects Response To Substance [23]
GTPase KRas (KRAS) OT78QCN8 RASK_HUMAN Increases Response To Substance [5]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Increases Response To Substance [5]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Affects Transport [24]
Dendrin (DDN) OTM52ZF5 DEND_HUMAN Increases Response To Substance [22]
Receptor tyrosine-protein kinase erbB-2 (ERBB2) OTOAUNCK ERBB2_HUMAN Increases Response To Substance [25]
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) OTOWDUNT PTEN_HUMAN Increases Response To Substance [21]
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) OTTOMI8J PK3CA_HUMAN Increases Response To Substance [25]
Pro-neuregulin-1, membrane-bound isoform (NRG1) OTZO6F1X NRG1_HUMAN Decreases Response To Substance [26]
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⏷ Show the Full List of 54 DOT(s)
Indication(s) of Obatoclax
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 2 [4]
Obatoclax Interacts with 3 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) TTL53M6 MCL1_HUMAN Inhibitor [4]
Apoptosis regulator Bcl-2 (BCL-2) TTJGNVC BCL2_HUMAN Inhibitor [4]
Apoptosis regulator Bcl-xL (BCL-xL) TTU1E82 B2CL1_HUMAN Inhibitor [4]
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References

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2 Phase II Randomized Preoperative Window-of-Opportunity Study of the PI3K Inhibitor Pictilisib Plus Anastrozole Compared With Anastrozole Alone in P... J Clin Oncol. 2016 Jun 10;34(17):1987-94.
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: 5682).
4 Phase II study of obatoclax mesylate (GX15-070), a small-molecule BCL-2 family antagonist, for patients with myelofibrosis. Clin Lymphoma Myeloma Leuk. 2010 Aug;10(4):285-9.
5 Phosphoinositide 3-kinase (PI3K) pathway alterations are associated with histologic subtypes and are predictive of sensitivity to PI3K inhibitors in lung cancer preclinical models. Clin Cancer Res. 2012 Dec 15;18(24):6771-83. doi: 10.1158/1078-0432.CCR-12-2347. Epub 2012 Nov 7.
6 Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44.
7 A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
8 The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer. J Med Chem. 2008 Sep 25;51(18):5522-32. doi: 10.1021/jm800295d.
9 Intermittent administration of MEK inhibitor GDC-0973 plus PI3K inhibitor GDC-0941 triggers robust apoptosis and tumor growth inhibition. Cancer Res. 2012 Jan 1;72(1):210-9. doi: 10.1158/0008-5472.CAN-11-1515. Epub 2011 Nov 14.
10 The PI3K inhibitor GDC-0941 combines with existing clinical regimens for superior activity in multiple myeloma. Oncogene. 2014 Jan 16;33(3):316-25. doi: 10.1038/onc.2012.594. Epub 2013 Jan 14.
11 GDC-0941 inhibits metastatic characteristics of thyroid carcinomas by targeting both the phosphoinositide-3 kinase (PI3K) and hypoxia-inducible factor-1 (HIF-1) pathways. J Clin Endocrinol Metab. 2011 Dec;96(12):E1934-43. doi: 10.1210/jc.2011-1426. Epub 2011 Oct 12.
12 The novel dual PI3K/mTOR inhibitor GDC-0941 synergizes with the MEK inhibitor U0126 in non-small cell lung cancer cells. Mol Med Rep. 2012 Feb;5(2):503-8. doi: 10.3892/mmr.2011.682. Epub 2011 Nov 16.
13 Nuclear phospho-Akt increase predicts synergy of PI3K inhibition and doxorubicin in breast and ovarian cancer. Sci Transl Med. 2010 Sep 8;2(48):48ra66. doi: 10.1126/scitranslmed.3000630.
14 GDC-0941 enhances the lysosomal compartment via TFEB and primes glioblastoma cells to lysosomal membrane permeabilization and cell death. Cancer Lett. 2013 Feb 1;329(1):27-36. doi: 10.1016/j.canlet.2012.09.007. Epub 2012 Sep 18.
15 Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941. Cancer Cell. 2009 May 5;15(5):429-40. doi: 10.1016/j.ccr.2009.03.020.
16 Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941. Mol Cancer Ther. 2009 Jul;8(7):1725-38. doi: 10.1158/1535-7163.MCT-08-1200. Epub 2009 Jul 7.
17 Simultaneous inhibition of pan-phosphatidylinositol-3-kinases and MEK as a potential therapeutic strategy in peripheral T-cell lymphomas. Haematologica. 2013 Jan;98(1):57-64. doi: 10.3324/haematol.2012.068510. Epub 2012 Jul 16.
18 Mechanisms of apoptosis induction by simultaneous inhibition of PI3K and FLT3-ITD in AML cells in the hypoxic bone marrow microenvironment. Cancer Lett. 2013 Feb 1;329(1):45-58. doi: 10.1016/j.canlet.2012.09.020. Epub 2012 Oct 2.
19 PI3K inhibition enhances doxorubicin-induced apoptosis in sarcoma cells. PLoS One. 2012;7(12):e52898. doi: 10.1371/journal.pone.0052898. Epub 2012 Dec 31.
20 Pim 1 kinase inhibitor ETP-45299 suppresses cellular proliferation and synergizes with PI3K inhibition. Cancer Lett. 2011 Jan 28;300(2):145-53. doi: 10.1016/j.canlet.2010.09.016. Epub 2010 Nov 3.
21 Isoform-specific phosphoinositide 3-kinase inhibitors exert distinct effects in solid tumors. Cancer Res. 2010 Feb 1;70(3):1164-72. doi: 10.1158/0008-5472.CAN-09-2525. Epub 2010 Jan 26.
22 Modulators of sensitivity and resistance to inhibition of PI3K identified in a pharmacogenomic screen of the NCI-60 human tumor cell line collection. PLoS One. 2012;7(9):e46518. doi: 10.1371/journal.pone.0046518. Epub 2012 Sep 28.
23 Regulatory roles of NAT10 in airway epithelial cell function and metabolism in pathological conditions. Cell Biol Toxicol. 2023 Aug;39(4):1237-1256. doi: 10.1007/s10565-022-09743-z. Epub 2022 Jul 25.
24 Role of P-glycoprotein and breast cancer resistance protein-1 in the brain penetration and brain pharmacodynamic activity of the novel phosphatidylinositol 3-kinase inhibitor GDC-0941. Drug Metab Dispos. 2010 Sep;38(9):1422-6. doi: 10.1124/dmd.110.034256. Epub 2010 Jun 3.
25 Predictive biomarkers of sensitivity to the phosphatidylinositol 3' kinase inhibitor GDC-0941 in breast cancer preclinical models. Clin Cancer Res. 2010 Jul 15;16(14):3670-83. doi: 10.1158/1078-0432.CCR-09-2828. Epub 2010 May 7.
26 Suppression of HER2/HER3-mediated growth of breast cancer cells with combinations of GDC-0941 PI3K inhibitor, trastuzumab, and pertuzumab. Clin Cancer Res. 2009 Jun 15;15(12):4147-56. doi: 10.1158/1078-0432.CCR-08-2814. Epub 2009 Jun 9.