Drug Information

Drug (ID: DG00275) and It's Reported Resistant Information
Name
Thalidomide
Synonyms
Algosediv; Asmadion; Asmaval; Bonbrain; Bonbrrin; Calmore; Calmorex; Contergan; Corronarobetin; Distaval; Distaxal; Distoval; Ectiluran; Enterosediv; Gastrinide; Glupan; Glutanon; Grippex; Hippuzon; Imidene; Isomin; Kedavon; Kevadon; Neaufatin; Neosedyn; Neosydyn; Nerosedyn; Neufatin; Neurodyn; Neurosedin; Neurosedym; Neurosedyn; Nevrodyn; Nibrol; Noctosediv; Noxodyn; Pangul; Pantosediv; Polygripan; Profarmil; Psycholiquid; Psychotablets; Quetimid; Quietoplex; Sandormin; Sedalis; Sedimide; Sedin; Sedisperil; Sedoval; Shinnibrol; Sleepan; Slipro; Softenil; Softenon; Synovir; Talargan; Talidomida; Talidomide; Talimol; Talismol; Talizer; Telagan; Telargan; Telargean; Tensival; Thaled; Thalidomidum; Thalin; Thalinette; Thalomid; Thalomide; Theophilcholine; Valgis; Valgraine; Yodomin; Celgene Brand of Thalidomide; Talidomide [DCIT]; Thalidomide Celgene; Thalidomide Pharmion; Asidon 3; ENMD 0995; IN1061; Thalidomine USP26; Alpha-Phthalimidoglutarimide; E-217; Imida-lab; Imidan (peyta); N-Phthalimidoglutamic acid imide; N-Phthaloylglutamimide; N-Phthalylglutamic acid imide; Poly-Giron; Predni-Sediv; Pro-Bam M; Pro-ban M; Sedalis sedi-lab; Shin-naito S; THALIDOMIDE (AIDS INITIATIVE); Talidomida [INN-Spanish]; Thaled (TN); Thalidomide (soluble form); Thalidomidum [INN-Latin]; Thalomid (TM); Thalomid (TN); Thalomid, Thalidomide; Alpha-N-Phthalylglutaramide; Thalidomide [USAN:INN:BAN]; Alpha-(N-Phthalimido)glutarimide; N-Phthalyl-glutaminsaeure-imid; N-Phthalyl-glutaminsaeure-imid [German]; Thalidomide (+ and-); Thalidomide (JAN/USP/INN); N-(2,6-Dioxo-3-piperidyl)phthalimide; (+)-Thalidomide; (+-)-Thalidomide; (+/-)-THALIDOMIDE; (inverted question mark)-Thalidomide; 2,6-Dioxo-3-phthalimidopiperidine; 3-Phthalimidoglutarimide
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Indication
In total 1 Indication(s)
Multiple myeloma [ICD-11: 2A83]
Approved
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
Multiple myeloma [ICD-11: 2A83]
[2], [3]
Target Tumor necrosis factor (TNF) TNFA_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C13H10N2O4
IsoSMILES
C1CC(=O)NC(=O)C1N2C(=O)C3=CC=CC=C3C2=O
InChI
1S/C13H10N2O4/c16-10-6-5-9(11(17)14-10)15-12(18)7-3-1-2-4-8(7)13(15)19/h1-4,9H,5-6H2,(H,14,16,17)
InChIKey
UEJJHQNACJXSKW-UHFFFAOYSA-N
PubChem CID
5426
ChEBI ID
CHEBI:74947
TTD Drug ID
D0U7GK
VARIDT ID
DR00461
INTEDE ID
DR1572
DrugBank ID
DB01041
Type(s) of Resistant Mechanism of This Drug
  EADR: Epigenetic Alteration of DNA, RNA or Protein
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
Click to Show/Hide the Resistance Disease of This Class
Multiple myeloma [ICD-11: 2A83]
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Zinc finger protein Aiolos (IKZF3) [4], [5]
Molecule Alteration Missense mutation
p.Q147H
 Molecule Info 
Resistant Disease Multiple myeloma [ICD-11: 2A83.0]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell proliferation Activation hsa05200
PI3K/RAS signaling pathway Regulation hsa04151
In Vitro Model Bone marrow Blood Homo sapiens (Human) N.A.
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Gene expression profiling assay; High-resolution copy number arrays assay; Whole-exome sequencing assay
Experiment for
Drug Resistance		 Longitudinal copy number aberration (CNA) analysis
Mechanism Description Resistance to immunomodulatory drugs (IMiD) and proteasome inhibitors was recently associated with mutations in IMiD response genes IRF4, CRBN, DDB1, CUL4A, CUL4B, IkZF1, IkZF2, and IkZF3 or in the proteasome inhibitor response genes PSMB5 and PSMG2, respectively. Mechanistically, bi-allelic loss of tumor-suppressor genes is a crucial mechanism, allowing units of selection to evade treatment-induced apoptosis with the acquisition of subsequent proliferative advantage leading to their outgrowth.
Key Molecule: Zinc finger protein Helios (IKZF2) [3]
Molecule Alteration Mutation
.
 Molecule Info 
Resistant Disease Multiple myeloma [ICD-11: 2A83.0]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell proliferation Activation hsa05200
PI3K/RAS signaling pathway Regulation hsa04151
In Vitro Model Bone marrow Blood Homo sapiens (Human) N.A.
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Gene expression profiling assay; High-resolution copy number arrays assay; Whole-exome sequencing assay
Experiment for
Drug Resistance		 Longitudinal copy number aberration (CNA) analysis
Mechanism Description Resistance to immunomodulatory drugs (IMiD) and proteasome inhibitors was recently associated with mutations in IMiD response genes IRF4, CRBN, DDB1, CUL4A, CUL4B, IkZF1, IkZF2, and IkZF3 or in the proteasome inhibitor response genes PSMB5 and PSMG2, respectively. Mechanistically, bi-allelic loss of tumor-suppressor genes is a crucial mechanism, allowing units of selection to evade treatment-induced apoptosis with the acquisition of subsequent proliferative advantage leading to their outgrowth.
Key Molecule: DNA-binding protein Ikaros (IKZF1) [3]
Molecule Alteration Mutation
.
 Molecule Info 
Resistant Disease Multiple myeloma [ICD-11: 2A83.0]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell proliferation Activation hsa05200
PI3K/RAS signaling pathway Regulation hsa04151
In Vitro Model Bone marrow Blood Homo sapiens (Human) N.A.
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Gene expression profiling assay; High-resolution copy number arrays assay; Whole-exome sequencing assay
Experiment for
Drug Resistance		 Longitudinal copy number aberration (CNA) analysis
Mechanism Description Resistance to immunomodulatory drugs (IMiD) and proteasome inhibitors was recently associated with mutations in IMiD response genes IRF4, CRBN, DDB1, CUL4A, CUL4B, IkZF1, IkZF2, and IkZF3 or in the proteasome inhibitor response genes PSMB5 and PSMG2, respectively. Mechanistically, bi-allelic loss of tumor-suppressor genes is a crucial mechanism, allowing units of selection to evade treatment-induced apoptosis with the acquisition of subsequent proliferative advantage leading to their outgrowth.
Key Molecule: DNA damage-binding protein 1 (DDB1) [3]
Molecule Alteration Mutation
.
 Molecule Info 
Resistant Disease Multiple myeloma [ICD-11: 2A83.0]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell proliferation Activation hsa05200
PI3K/RAS signaling pathway Regulation hsa04151
In Vitro Model Bone marrow Blood Homo sapiens (Human) N.A.
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Gene expression profiling assay; High-resolution copy number arrays assay; Whole-exome sequencing assay
Experiment for
Drug Resistance		 Longitudinal copy number aberration (CNA) analysis
Mechanism Description Resistance to immunomodulatory drugs (IMiD) and proteasome inhibitors was recently associated with mutations in IMiD response genes IRF4, CRBN, DDB1, CUL4A, CUL4B, IkZF1, IkZF2, and IkZF3 or in the proteasome inhibitor response genes PSMB5 and PSMG2, respectively. Mechanistically, bi-allelic loss of tumor-suppressor genes is a crucial mechanism, allowing units of selection to evade treatment-induced apoptosis with the acquisition of subsequent proliferative advantage leading to their outgrowth.
Key Molecule: Cullin-4B (CUL4B) [3]
Molecule Alteration Mutation
.
 Molecule Info 
Resistant Disease Multiple myeloma [ICD-11: 2A83.0]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell proliferation Activation hsa05200
PI3K/RAS signaling pathway Regulation hsa04151
In Vitro Model Bone marrow Blood Homo sapiens (Human) N.A.
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Gene expression profiling assay; High-resolution copy number arrays assay; Whole-exome sequencing assay
Experiment for
Drug Resistance		 Longitudinal copy number aberration (CNA) analysis
Mechanism Description Resistance to immunomodulatory drugs (IMiD) and proteasome inhibitors was recently associated with mutations in IMiD response genes IRF4, CRBN, DDB1, CUL4A, CUL4B, IkZF1, IkZF2, and IkZF3 or in the proteasome inhibitor response genes PSMB5 and PSMG2, respectively. Mechanistically, bi-allelic loss of tumor-suppressor genes is a crucial mechanism, allowing units of selection to evade treatment-induced apoptosis with the acquisition of subsequent proliferative advantage leading to their outgrowth.
Key Molecule: Cullin-4A (CUL4A) [3]
Molecule Alteration Mutation
.
 Molecule Info 
Resistant Disease Multiple myeloma [ICD-11: 2A83.0]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell proliferation Activation hsa05200
PI3K/RAS signaling pathway Regulation hsa04151
In Vitro Model Bone marrow Blood Homo sapiens (Human) N.A.
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Gene expression profiling assay; High-resolution copy number arrays assay; Whole-exome sequencing assay
Experiment for
Drug Resistance		 Longitudinal copy number aberration (CNA) analysis
Mechanism Description Resistance to immunomodulatory drugs (IMiD) and proteasome inhibitors was recently associated with mutations in IMiD response genes IRF4, CRBN, DDB1, CUL4A, CUL4B, IkZF1, IkZF2, and IkZF3 or in the proteasome inhibitor response genes PSMB5 and PSMG2, respectively. Mechanistically, bi-allelic loss of tumor-suppressor genes is a crucial mechanism, allowing units of selection to evade treatment-induced apoptosis with the acquisition of subsequent proliferative advantage leading to their outgrowth.
Key Molecule: Protein cereblon (CRBN) [2], [3]
Molecule Alteration Truncating mutation
p.R283K
 Molecule Info 
Resistant Disease Multiple myeloma [ICD-11: 2A83.0]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell proliferation Activation hsa05200
PI3K/RAS signaling pathway Regulation hsa04151
In Vitro Model Bone marrow Blood Homo sapiens (Human) N.A.
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Gene expression profiling assay; High-resolution copy number arrays assay; Whole-exome sequencing assay
Experiment for
Drug Resistance		 Longitudinal copy number aberration (CNA) analysis
Mechanism Description Resistance to immunomodulatory drugs (IMiD) and proteasome inhibitors was recently associated with mutations in IMiD response genes IRF4, CRBN, DDB1, CUL4A, CUL4B, IkZF1, IkZF2, and IkZF3 or in the proteasome inhibitor response genes PSMB5 and PSMG2, respectively. Mechanistically, bi-allelic loss of tumor-suppressor genes is a crucial mechanism, allowing units of selection to evade treatment-induced apoptosis with the acquisition of subsequent proliferative advantage leading to their outgrowth.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-202 [1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Multiple myeloma [ICD-11: 2A83.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
JNk/SAPk signaling pathway Regulation hsa05161
In Vitro Model U266 cells Bone marrow Homo sapiens (Human) CVCL_0566
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 WST assay
Mechanism Description miR-202 was functioned as a modulator of BAFF expression. miR-202 over-expression sensitized MM cells to bortezomib (Bort) but less to Thalidomide (Thal) and dexamethasone (Dex). miR-202 mimics in combination with Bort inhibited MM cell survival more effectively as compared with Bort treatment alone. Our study also provided experimental evidence that JNk/SAPk signaling pathway was involved in the regulatory effect of miR-202 on drug resistance of MM cells.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Tumor necrosis factor ligand superfamily member 13B (TNFSF13B) [1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Multiple myeloma [ICD-11: 2A83.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
JNk/SAPk signaling pathway Regulation hsa05161
In Vitro Model U266 cells Bone marrow Homo sapiens (Human) CVCL_0566
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 WST assay
Mechanism Description miR-202 was functioned as a modulator of BAFF expression. miR-202 over-expression sensitized MM cells to bortezomib (Bort) but less to Thalidomide (Thal) and dexamethasone (Dex). miR-202 mimics in combination with Bort inhibited MM cell survival more effectively as compared with Bort treatment alone. Our study also provided experimental evidence that JNk/SAPk signaling pathway was involved in the regulatory effect of miR-202 on drug resistance of MM cells.
References
Ref 1 Study on the Association Between miRNA-202 Expression and Drug Sensitivity in Multiple Myeloma Cells. Pathol Oncol Res. 2016 Jul;22(3):531-9. doi: 10.1007/s12253-015-0035-4. Epub 2015 Dec 21.
Ref 2 Extramedullary myeloma whole genome sequencing reveals novel mutations in Cereblon, proteasome subunit G2 and the glucocorticoid receptor in multi drug resistant disease. Br J Haematol. 2013 Jun;161(5):748-51. doi: 10.1111/bjh.12291. Epub 2013 Mar 11.
Ref 3 Clonal selection and double-hit events involving tumor suppressor genes underlie relapse in myeloma. Blood. 2016 Sep 29;128(13):1735-44. doi: 10.1182/blood-2016-06-723007. Epub 2016 Aug 11.
Ref 4 Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science. 2014 Jan 17;343(6168):301-5. doi: 10.1126/science.1244851. Epub 2013 Nov 29.
Ref 5 Clonal rat parathyroid cell line expresses a parathyroid hormone-related peptide but not parathyroid hormone itself. Biochem Biophys Res Commun. 1989 Jul 14;162(1):108-15. doi: 10.1016/0006-291x(89)91969-4.

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