Details of the Drug Combination

General Information of Drug Combination (ID: DC8AFVH)

Drug Combination Name
Thalidomide NV-07a
Indication
Disease Entry Status REF
Coronavirus Disease 2019 (COVID-19) Phase 2 [1]
Component Drugs Thalidomide   DM70BU5 NV-07a   DMWLQV8
Small molecular drug N.A.

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Thalidomide
Disease Entry ICD 11 Status REF
Adult T-cell leukemia/lymphoma N.A. Approved [2]
Advanced cancer 2A00-2F9Z Approved [2]
Complex regional pain syndrome type 1 N.A. Approved [2]
Hepatosplenic T-cell lymphoma N.A. Approved [2]
Large granular lymphocytic leukemia 2A90.1 Approved [2]
Leukemia N.A. Approved [2]
MALT lymphoma N.A. Approved [2]
Multiple myeloma 2A83 Approved [3]
Nodal marginal zone lymphoma 2A85.0 Approved [2]
Pain MG30-MG3Z Approved [2]
Plasma cell myeloma 2A83.1 Approved [2]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified N.A. Approved [2]
Prolymphocytic leukaemia 2A82.1 Approved [2]
Recurrent adult burkitt lymphoma 2A85.6 Approved [2]
Small intestine lymphoma N.A. Approved [2]
Splenic marginal zone lymphoma N.A. Approved [2]
Testicular lymphoma N.A. Approved [2]
Urinary bladder neoplasm N.A. Approved [2]
Waldenstrom macroglobulinemia 2A85.4 Approved [2]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2 [4]
Colon cancer 2B90.Z Investigative [2]
Thalidomide Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Tumor necrosis factor (TNF) TTF8CQI TNFA_HUMAN Inhibitor [12]
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Thalidomide Interacts with 9 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Metabolism [13]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [14]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Metabolism [15]
Cytochrome P450 2C18 (CYP2C18) DEZMWRE CP2CI_HUMAN Metabolism [16]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [16]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [16]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [13]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [17]
Prostaglandin G/H synthase 1 (COX-1) DE073H6 PGH1_HUMAN Metabolism [15]
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⏷ Show the Full List of 9 DME(s)
Thalidomide Interacts with 70 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Increases Hydroxylation [14]
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Increases Expression [18]
Tumor necrosis factor receptor superfamily member 10A (TNFRSF10A) OTBPCU2O TR10A_HUMAN Decreases Expression [19]
Voltage-dependent L-type calcium channel subunit beta-4 (CACNB4) OTYAI1UO CACB4_HUMAN Decreases Expression [20]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Decreases Expression [19]
CASP8 and FADD-like apoptosis regulator (CFLAR) OTX14BAS CFLAR_HUMAN Decreases Expression [21]
Kalirin (KALRN) OT8WRCBH KALRN_HUMAN Decreases Expression [20]
Protein phosphatase 1 regulatory subunit 15A (PPP1R15A) OTYG179K PR15A_HUMAN Increases Expression [22]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Increases Expression [22]
C-reactive protein (CRP) OT0RFT8F CRP_HUMAN Decreases Expression [23]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Increases Expression [22]
Calbindin (CALB1) OTM7IXDG CALB1_HUMAN Decreases Expression [11]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Decreases Expression [24]
Homeobox protein Hox-B7 (HOXB7) OTC7WYU8 HXB7_HUMAN Increases Expression [6]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [10]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Decreases Activity [25]
Transcriptional activator Myb (MYB) OTJH64IV MYB_HUMAN Decreases Activity [26]
Cadherin-1 (CDH1) OTFJMXPM CADH1_HUMAN Increases Expression [9]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Decreases Expression [22]
HLA class I histocompatibility antigen, alpha chain E (HLA-E) OTX1CTFB HLAE_HUMAN Affects Expression [27]
Homeobox protein Hox-B9 (HOXB9) OTMVHQOU HXB9_HUMAN Increases Expression [6]
Cadherin-2 (CDH2) OTH0Y56P CADH2_HUMAN Decreases Expression [9]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) OT2D9DOV TNR1A_HUMAN Decreases Expression [28]
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) OTDS2EAR TNR1B_HUMAN Decreases Expression [28]
Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1) OTGP6GA4 NR4A1_HUMAN Increases Expression [22]
Paired box protein Pax-3 (PAX3) OTN5PJZV PAX3_HUMAN Decreases Expression [6]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Decreases Expression [19]
DnaJ homolog subfamily B member 1 (DNAJB1) OTCOSEVH DNJB1_HUMAN Increases Expression [22]
Paired box protein Pax-6 (PAX6) OTOC9876 PAX6_HUMAN Increases Expression [6]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [10]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [10]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [22]
Interleukin-6 receptor subunit beta (IL6ST) OT1N9C70 IL6RB_HUMAN Decreases Expression [28]
Nuclear receptor subfamily 4 group A member 2 (NR4A2) OT3F9IR2 NR4A2_HUMAN Increases Expression [22]
Tumor necrosis factor ligand superfamily member 6 (FASLG) OTZARCHH TNFL6_HUMAN Decreases Expression [19]
Homeobox protein MOX-1 (MEOX1) OTJEMT2D MEOX1_HUMAN Decreases Expression [6]
Tumor necrosis factor ligand superfamily member 10 (TNFSF10) OT4PXBTA TNF10_HUMAN Decreases Expression [19]
Protein FosB (FOSB) OTW6C05J FOSB_HUMAN Increases Expression [22]
Sorting nexin-16 (SNX16) OTYQ0TV4 SNX16_HUMAN Increases Expression [22]
Neurexin-1-beta (NRXN1) OTJN1JQA NRX1B_HUMAN Decreases Expression [20]
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) OTOWDUNT PTEN_HUMAN Increases Expression [29]
Cytochrome c (CYCS) OTBFALJD CYC_HUMAN Increases Expression [30]
Transcription factor RelB (RELB) OTU3QYEF RELB_HUMAN Increases Expression [22]
Cyclic AMP-responsive element-binding protein 5 (CREB5) OTJDUJPI CREB5_HUMAN Decreases Expression [20]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Expression [21]
Mesoderm posterior protein 2 (MESP2) OT7H4LYA MESP2_HUMAN Decreases Expression [6]
Transcription factor 15 (TCF15) OTA6UCWC TCF15_HUMAN Decreases Expression [6]
Dual specificity protein phosphatase 8 (DUSP8) OTPLMPG9 DUS8_HUMAN Increases Expression [22]
Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein (HERPUD1) OT9EROL6 HERP1_HUMAN Increases Expression [22]
Mitogen-activated protein kinase 14 (MAPK14) OT5TCO3O MK14_HUMAN Increases Phosphorylation [10]
Ephrin type-A receptor 10 (EPHA10) OT1XJGFG EPHAA_HUMAN Decreases Expression [20]
Oligodendrocyte transcription factor 3 (OLIG3) OTU8XLAF OLIG3_HUMAN Increases Expression [6]
CREB3 regulatory factor (CREBRF) OT2GK1HI CRERF_HUMAN Increases Expression [22]
Complexin-3 (CPLX3) OT0YTMN2 CPLX3_HUMAN Decreases Expression [20]
Heat shock protein 105 kDa (HSPH1) OTVRR73T HS105_HUMAN Increases Expression [22]
Tribbles homolog 3 (TRIB3) OTG5OS7X TRIB3_HUMAN Increases Expression [22]
Eyes absent homolog 1 (EYA1) OTHU807A EYA1_HUMAN Decreases Expression [6]
Synaptotagmin-15 (SYT15) OT7Q088G SYT15_HUMAN Decreases Expression [20]
Neurogenin-2 (NEUROG2) OTAEMIGT NGN2_HUMAN Increases Expression [6]
Synaptotagmin-4 (SYT4) OTA1D7VL SYT4_HUMAN Increases Expression [20]
Frizzled-8 (FZD8) OTZ9IRFL FZD8_HUMAN Decreases Expression [11]
Transcription factor SOX-17 (SOX17) OT9H4WWE SOX17_HUMAN Decreases Localization [11]
Serine/threonine-protein kinase LATS2 (LATS2) OT6XO8JP LATS2_HUMAN Increases Expression [22]
Inhibitor of growth protein 3 (ING3) OTDIJXFP ING3_HUMAN Increases Expression [22]
Programmed cell death 1 ligand 1 (CD274) OTJ0VFDL PD1L1_HUMAN Decreases Expression [9]
DnaJ homolog subfamily B member 9 (DNAJB9) OT38EQT6 DNJB9_HUMAN Increases Expression [22]
DnaJ homolog subfamily B member 4 (DNAJB4) OTUD01BK DNJB4_HUMAN Increases Expression [22]
Sal-like protein 4 (SALL4) OTC08PR5 SALL4_HUMAN Increases Expression [31]
Plasminogen activator inhibitor 2 (SERPINB2) OT72QLZB PAI2_HUMAN Increases Response To Substance [32]
Phospholipid-transporting ATPase ABCA1 (ABCA1) OT94G6BQ ABCA1_HUMAN Increases Response To Substance [32]
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⏷ Show the Full List of 70 DOT(s)
Indication(s) of NV-07a
Disease Entry ICD 11 Status REF
Inflammatory bowel disease DD72 Investigative [5]
NV-07a Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Hormone unspecific (HOM) TTXPQW1 NOUNIPROTAC Modulator [5]
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References

1 ClinicalTrials.gov (NCT04273581) The Efficacy and Safety of Thalidomide Combined With Low-dose Hormones in the Treatment of Severe COVID-19. U.S. National Institutes of Health.
2 Thalidomide FDA Label
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: 7327).
4 ClinicalTrials.gov (NCT04273529) The Efficacy and Safety of Thalidomide in the Adjuvant Treatment of Moderate New Coronavirus (COVID-19) Pneumonia. U.S. National Institutes of Health.
5 UV radiation-induced immunosuppression is greater in men and prevented by topical nicotinamide. J Invest Dermatol. 2008 Feb;128(2):447-54.
6 Exposure-based assessment of chemical teratogenicity using morphogenetic aggregates of human embryonic stem cells. Reprod Toxicol. 2020 Jan;91:74-91. doi: 10.1016/j.reprotox.2019.10.004. Epub 2019 Nov 8.
7 Inhibitory Effects of Arsenic Trioxide and Thalidomide on Angiogenesis and Vascular Endothelial Growth Factor Expression in Leukemia Cells. Asian Pac J Cancer Prev. 2018 Apr 27;19(4):1127-1134. doi: 10.22034/APJCP.2018.19.4.1127.
8 The enhancement of radiosensitivity in human esophageal carcinoma cells by thalidomide and its potential mechanism. Cancer Biother Radiopharm. 2011 Apr;26(2):219-27. doi: 10.1089/cbr.2010.0897.
9 Thalidomide suppresses angiogenesis and immune evasion via lncRNA FGD5-AS1/miR-454-3p/ZEB1 axis-mediated VEGFA expression and PD-1/PD-L1 checkpoint in NSCLC. Chem Biol Interact. 2021 Nov 1;349:109652. doi: 10.1016/j.cbi.2021.109652. Epub 2021 Sep 11.
10 Antimyeloma activity of two novel N-substituted and tetraflourinated thalidomide analogs. Leukemia. 2005 Jul;19(7):1253-61. doi: 10.1038/sj.leu.2403776.
11 A high-throughput screen for teratogens using human pluripotent stem cells. Toxicol Sci. 2014 Jan;137(1):76-90. doi: 10.1093/toxsci/kft239. Epub 2013 Oct 23.
12 Efficacy of different thalidomide regimens for patients with multiple myeloma and its relationship with TNF-alpha level. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008 Dec;16(6):1312-5.
13 Metabolism of thalidomide in human microsomes, cloned human cytochrome P-450 isozymes, and Hansen's disease patients. J Biochem Mol Toxicol. 2000;14(3):140-7.
14 Human liver microsomal cytochrome P450 3A enzymes involved in thalidomide 5-hydroxylation and formation of a glutathione conjugate. Chem Res Toxicol. 2010 Jun 21;23(6):1018-24.
15 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
16 Thalidomide metabolism by the CYP2C subfamily. Clin Cancer Res. 2002 Jun;8(6):1964-73.
17 Pharmacogenetic associations of CYP2C19 genotype with in vivo metabolisms and pharmacological effects of thalidomide. Cancer Biol Ther. 2002 Nov-Dec;1(6):669-73.
18 Induction of human cytochrome P450 3A enzymes in cultured placental cells by thalidomide and relevance to bioactivation and toxicity. J Toxicol Sci. 2017;42(3):343-348.
19 Stimulation of erythropoiesis by thalidomide in multiple myeloma patients: its influence on FasL, TRAIL and their receptors on erythroblasts. Haematologica. 2006 Mar;91(3):386-9.
20 Early Transcriptomic Changes upon Thalidomide Exposure Influence the Later Neuronal Development in Human Embryonic Stem Cell-Derived Spheres. Int J Mol Sci. 2020 Aug 3;21(15):5564. doi: 10.3390/ijms21155564.
21 NF-kappaB protects Beh?et's disease T cells against CD95-induced apoptosis up-regulating antiapoptotic proteins. Arthritis Rheum. 2005 Jul;52(7):2179-91. doi: 10.1002/art.21145.
22 Polyunsaturated fatty acids synergize with lipid droplet binding thalidomide analogs to induce oxidative stress in cancer cells. Lipids Health Dis. 2010 Jun 2;9:56. doi: 10.1186/1476-511X-9-56.
23 Intractable insomnia after cessation of treatment with thalidomide. Gastroenterology. 2001 May;120(6):1567-8. doi: 10.1053/gast.2001.24495.
24 Long-term thalidomide therapy resulted in lack of mdr1 gene expression in a patient with primary resistant multiple myeloma. Leukemia. 2005 Aug;19(8):1497-9. doi: 10.1038/sj.leu.2403811.
25 Combination of thalidomide and cisplatin in an head and neck squamous cell carcinomas model results in an enhanced antiangiogenic activity in vitro and in vivo. Int J Cancer. 2007 Oct 15;121(8):1697-704. doi: 10.1002/ijc.22867.
26 Thalidomide alters c-MYB and PIM-1 signaling in K-562 cells. Pharmacol Res. 2006 Aug;54(2):91-6. doi: 10.1016/j.phrs.2006.02.010. Epub 2006 Mar 8.
27 Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
28 Circulating endothelial progenitor cells in multiple myeloma: implications and significance. Blood. 2005 Apr 15;105(8):3286-94. doi: 10.1182/blood-2004-06-2101. Epub 2004 Dec 23.
29 Mechanism of thalidomide to enhance cytotoxicity of temozolomide in U251-MG glioma cells in vitro. Chin Med J (Engl). 2009 Jun 5;122(11):1260-6.
30 Thalidomide inhibits growth of tumors through COX-2 degradation independent of antiangiogenesis. Vascul Pharmacol. 2005 Aug;43(2):112-9. doi: 10.1016/j.vph.2005.04.003.
31 Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome. Elife. 2018 Aug 1;7:e38430. doi: 10.7554/eLife.38430.
32 Genetic factors underlying the risk of thalidomide-related neuropathy in patients with multiple myeloma. J Clin Oncol. 2011 Mar 1;29(7):797-804. doi: 10.1200/JCO.2010.28.0792. Epub 2011 Jan 18.