Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCDPH5D)

DOT Name 3-mercaptopyruvate sulfurtransferase (MPST)
Synonyms MST; EC 2.8.1.2
Gene Name MPST
Related Disease
Leishmaniasis ( )
Acute myelogenous leukaemia ( )
Alzheimer disease ( )
Breast cancer ( )
Breast carcinoma ( )
Carcinoma ( )
Carcinoma of liver and intrahepatic biliary tract ( )
Colon adenocarcinoma ( )
Colon cancer ( )
Colon carcinoma ( )
Fatty liver disease ( )
Hepatocellular carcinoma ( )
Hyperthyroidism ( )
Insomnia ( )
Kidney neoplasm ( )
Liver cancer ( )
Non-alcoholic fatty liver disease ( )
Non-insulin dependent diabetes ( )
Post-traumatic stress disorder ( )
Promyelocytic leukaemia ( )
Bone osteosarcoma ( )
Brain neoplasm ( )
Melanoma ( )
Osteosarcoma ( )
Pancreatic cancer ( )
Plasma cell myeloma ( )
Rhabdomyosarcoma ( )
Acute lymphocytic leukaemia ( )
Adult glioblastoma ( )
Advanced cancer ( )
Astrocytoma ( )
Childhood acute lymphoblastic leukemia ( )
Glioblastoma multiforme ( )
High blood pressure ( )
Mesothelioma ( )
Neuroblastoma ( )
Non-small-cell lung cancer ( )
Osteoarthritis ( )
T-cell acute lymphoblastic leukaemia ( )
Type-1/2 diabetes ( )
Encephalopathy due to beta-mercaptolactate-cysteine disulfiduria ( )
UniProt ID
THTM_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
3OLH; 4JGT
EC Number
2.8.1.2
Pfam ID
PF00581
Sequence
MASPQLCRALVSAQWVAEALRAPRAGQPLQLLDASWYLPKLGRDARREFEERHIPGAAFF
DIDQCSDRTSPYDHMLPGAEHFAEYAGRLGVGAATHVVIYDASDQGLYSAPRVWWMFRAF
GHHAVSLLDGGLRHWLRQNLPLSSGKSQPAPAEFRAQLDPAFIKTYEDIKENLESRRFQV
VDSRATGRFRGTEPEPRDGIEPGHIPGTVNIPFTDFLSQEGLEKSPEEIRHLFQEKKVDL
SKPLVATCGSGVTACHVALGAYLCGKPDVPIYDGSWVEWYMRARPEDVISEGRGKTH
Function
Transfer of a sulfur ion to cyanide or to other thiol compounds. Also has weak rhodanese activity. Detoxifies cyanide and is required for thiosulfate biosynthesis. Acts as an antioxidant. In combination with cysteine aminotransferase (CAT), contributes to the catabolism of cysteine and is an important producer of hydrogen sulfide in the brain, retina and vascular endothelial cells. Hydrogen sulfide H(2)S is an important synaptic modulator, signaling molecule, smooth muscle contractor and neuroprotectant. Its production by the 3MST/CAT pathway is regulated by calcium ions.
KEGG Pathway
Cysteine and methionine metabolism (hsa00270 )
Sulfur metabolism (hsa00920 )
Metabolic pathways (hsa01100 )
Sulfur relay system (hsa04122 )
Reactome Pathway
Degradation of cysteine and homocysteine (R-HSA-1614558 )
BioCyc Pathway
MetaCyc:HS05177-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

41 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Leishmaniasis DISABTW7 Definitive Biomarker [1]
Acute myelogenous leukaemia DISCSPTN Strong Biomarker [2]
Alzheimer disease DISF8S70 Strong Biomarker [3]
Breast cancer DIS7DPX1 Strong Altered Expression [4]
Breast carcinoma DIS2UE88 Strong Altered Expression [4]
Carcinoma DISH9F1N Strong Altered Expression [5]
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W Strong Biomarker [6]
Colon adenocarcinoma DISDRE0J Strong Biomarker [5]
Colon cancer DISVC52G Strong Biomarker [7]
Colon carcinoma DISJYKUO Strong Biomarker [7]
Fatty liver disease DIS485QZ Strong Genetic Variation [8]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [9]
Hyperthyroidism DISX87ZH Strong Altered Expression [10]
Insomnia DIS0AFR7 Strong Biomarker [11]
Kidney neoplasm DISBNZTN Strong Biomarker [12]
Liver cancer DISDE4BI Strong Biomarker [6]
Non-alcoholic fatty liver disease DISDG1NL Strong Altered Expression [8]
Non-insulin dependent diabetes DISK1O5Z Strong Biomarker [13]
Post-traumatic stress disorder DISHL1EY Strong Biomarker [11]
Promyelocytic leukaemia DISYGG13 Strong Biomarker [14]
Bone osteosarcoma DIST1004 moderate Biomarker [15]
Brain neoplasm DISY3EKS moderate Biomarker [15]
Melanoma DIS1RRCY moderate Biomarker [16]
Osteosarcoma DISLQ7E2 moderate Biomarker [15]
Pancreatic cancer DISJC981 moderate Biomarker [17]
Plasma cell myeloma DIS0DFZ0 moderate Biomarker [18]
Rhabdomyosarcoma DISNR7MS moderate Altered Expression [19]
Acute lymphocytic leukaemia DISPX75S Limited Genetic Variation [20]
Adult glioblastoma DISVP4LU Limited Biomarker [21]
Advanced cancer DISAT1Z9 Limited Biomarker [5]
Astrocytoma DISL3V18 Limited Biomarker [21]
Childhood acute lymphoblastic leukemia DISJ5D6U Limited Genetic Variation [20]
Glioblastoma multiforme DISK8246 Limited Biomarker [21]
High blood pressure DISY2OHH Limited Biomarker [22]
Mesothelioma DISKWK9M Limited Biomarker [23]
Neuroblastoma DISVZBI4 Limited Biomarker [21]
Non-small-cell lung cancer DIS5Y6R9 Limited Biomarker [24]
Osteoarthritis DIS05URM Limited Altered Expression [25]
T-cell acute lymphoblastic leukaemia DIS17AI2 Limited Biomarker [20]
Type-1/2 diabetes DISIUHAP Limited Biomarker [22]
Encephalopathy due to beta-mercaptolactate-cysteine disulfiduria DISOJMSO No Known Autosomal recessive [26]
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⏷ Show the Full List of 41 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 2 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Temozolomide DMKECZD Approved 3-mercaptopyruvate sulfurtransferase (MPST) affects the response to substance of Temozolomide. [37]
DTI-015 DMXZRW0 Approved 3-mercaptopyruvate sulfurtransferase (MPST) affects the response to substance of DTI-015. [37]
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11 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of 3-mercaptopyruvate sulfurtransferase (MPST). [27]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of 3-mercaptopyruvate sulfurtransferase (MPST). [28]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of 3-mercaptopyruvate sulfurtransferase (MPST). [29]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of 3-mercaptopyruvate sulfurtransferase (MPST). [30]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of 3-mercaptopyruvate sulfurtransferase (MPST). [31]
Testosterone DM7HUNW Approved Testosterone decreases the expression of 3-mercaptopyruvate sulfurtransferase (MPST). [32]
Selenium DM25CGV Approved Selenium increases the expression of 3-mercaptopyruvate sulfurtransferase (MPST). [33]
Irinotecan DMP6SC2 Approved Irinotecan decreases the expression of 3-mercaptopyruvate sulfurtransferase (MPST). [34]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of 3-mercaptopyruvate sulfurtransferase (MPST). [33]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of 3-mercaptopyruvate sulfurtransferase (MPST). [35]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of 3-mercaptopyruvate sulfurtransferase (MPST). [36]
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⏷ Show the Full List of 11 Drug(s)

References

1 Effectiveness of an immunohistochemical protocol for Leishmania detection in different clinical forms of American tegumentary leishmaniasis.Parasitol Int. 2017 Feb;66(1):884-888. doi: 10.1016/j.parint.2016.10.003. Epub 2016 Oct 8.
2 Current state of nonengrafting donor leukocyte infusion (focus on microtransplantation for acute myeloid leukemia).Curr Opin Hematol. 2019 Nov;26(6):373-378. doi: 10.1097/MOH.0000000000000539.
3 ApoE and SNAP-25 Polymorphisms Predict the Outcome of Multidimensional Stimulation Therapy Rehabilitation in Alzheimer's Disease.Neurorehabil Neural Repair. 2016 Oct;30(9):883-93. doi: 10.1177/1545968316642523. Epub 2016 Apr 13.
4 MST-312 Alters Telomere Dynamics, Gene Expression Profiles and Growth in Human Breast Cancer Cells.J Nutrigenet Nutrigenomics. 2014;7(4-6):283-98. doi: 10.1159/000381346. Epub 2015 May 27.
5 Potential role of the 3-mercaptopyruvate sulfurtransferase (3-MST)-hydrogen sulfide (H(2)S) pathway in cancer cells.Pharmacol Res. 2020 Apr;154:104083. doi: 10.1016/j.phrs.2018.11.034. Epub 2018 Nov 27.
6 Prognostic impact of transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation in patients with unresectable hepatocellular carcinoma: Comparison with TACE alone using decision-tree analysis after propensity score matching.Hepatol Res. 2019 Aug;49(8):919-928. doi: 10.1111/hepr.13348. Epub 2019 May 13.
7 N-Acetylcysteine Serves as Substrate of 3-Mercaptopyruvate Sulfurtransferase and Stimulates Sulfide Metabolism in Colon Cancer Cells.Cells. 2019 Aug 4;8(8):828. doi: 10.3390/cells8080828.
8 Fatty acids promote fatty liver disease via the dysregulation of 3-mercaptopyruvate sulfurtransferase/hydrogen sulfide pathway.Gut. 2018 Dec;67(12):2169-2180. doi: 10.1136/gutjnl-2017-313778. Epub 2017 Sep 6.
9 Tum-1, a tumstatin fragment, gene delivery into hepatocellular carcinoma suppresses tumor growth through inhibiting angiogenesis.Int J Oncol. 2008 Jul;33(1):33-40.
10 Altered gene expression of hydrogen sulfide-producing enzymes in the liver and muscles tissues of hyperthyroid rats.J Cell Physiol. 2019 Aug;234(10):17937-17945. doi: 10.1002/jcp.28426. Epub 2019 Mar 1.
11 Associations between traumatic brain injury from intimate partner violence and future psychosocial health risks in women.Compr Psychiatry. 2019 Jul;92:13-21. doi: 10.1016/j.comppsych.2019.05.001. Epub 2019 May 14.
12 Endogenous H(2)S producing enzymes are involved in apoptosis induction in clear cell renal cell carcinoma.BMC Cancer. 2018 May 24;18(1):591. doi: 10.1186/s12885-018-4508-1.
13 Proteomic profiling of non-obese type 2 diabetic skeletal muscle.Int J Mol Med. 2010 Mar;25(3):445-58. doi: 10.3892/ijmm_00000364.
14 MST-312 induces G2/M cell cycle arrest and apoptosis in APL cells through inhibition of telomerase activity and suppression of NF-B pathway.Tumour Biol. 2015 Nov;36(11):8425-37. doi: 10.1007/s13277-015-3575-z. Epub 2015 May 29.
15 Targeting DNA-PKcs and telomerase in brain tumour cells.Mol Cancer. 2014 Oct 13;13:232. doi: 10.1186/1476-4598-13-232.
16 Role of the cystathionine lyase/hydrogen sulfide pathway in human melanoma progression.Pigment Cell Melanoma Res. 2015 Jan;28(1):61-72. doi: 10.1111/pcmr.12312. Epub 2014 Oct 6.
17 The MST4-MOB4 complex disrupts the MST1-MOB1 complex in the Hippo-YAP pathway and plays a pro-oncogenic role in pancreatic cancer.J Biol Chem. 2018 Sep 14;293(37):14455-14469. doi: 10.1074/jbc.RA118.003279. Epub 2018 Aug 2.
18 Telomerase inhibitor MST-312 induces apoptosis of multiple myeloma cells and down-regulation of anti-apoptotic, proliferative and inflammatory genes.Life Sci. 2019 Jul 1;228:66-71. doi: 10.1016/j.lfs.2019.04.060. Epub 2019 Apr 25.
19 Loss of MST/Hippo Signaling in a Genetically Engineered Mouse Model of Fusion-Positive Rhabdomyosarcoma Accelerates Tumorigenesis.Cancer Res. 2018 Oct 1;78(19):5513-5520. doi: 10.1158/0008-5472.CAN-17-3912. Epub 2018 Aug 9.
20 Frequent deletions at 12q14.3 chromosomal locus in adult acute lymphoblastic leukemia.Genes Chromosomes Cancer. 2005 Jan;42(1):87-94. doi: 10.1002/gcc.20116.
21 Hydrogen sulfide generation from l-cysteine in the human glioblastoma-astrocytoma U-87 MG and neuroblastoma SHSY5Y cell lines.Acta Biochim Pol. 2017;64(1):171-176. doi: 10.18388/abp.2016_1394. Epub 2017 Mar 14.
22 Impact of long-term antihypertensive and antidiabetic medications on the prognosis of post-surgical colorectal cancer: the Fujian prospective investigation of cancer (FIESTA) study.Aging (Albany NY). 2018 May 24;10(5):1166-1181. doi: 10.18632/aging.101459.
23 CD9 expression as a favorable prognostic marker for patients with malignant mesothelioma.Oncol Rep. 2013 Jan;29(1):21-8. doi: 10.3892/or.2012.2116. Epub 2012 Oct 31.
24 Non-surgical therapy for patients with advanced non-small cell lung cancer.Respirology. 1998 Sep;3(3):151-7. doi: 10.1111/j.1440-1843.1998.tb00114.x.
25 Hydrogen sulfide biosynthesis is impaired in the osteoarthritic joint.Int J Biometeorol. 2020 Jun;64(6):997-1010. doi: 10.1007/s00484-019-01823-w. Epub 2019 Nov 16.
26 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
27 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
28 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
29 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
30 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
31 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
32 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
33 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
34 Gene expression profile of colon cancer cell lines treated with SN-38. Chemotherapy. 2010;56(1):17-25. doi: 10.1159/000287353. Epub 2010 Feb 24.
35 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
36 Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
37 Tumor necrosis factor-alpha-induced protein 3 as a putative regulator of nuclear factor-kappaB-mediated resistance to O6-alkylating agents in human glioblastomas. J Clin Oncol. 2006 Jan 10;24(2):274-87. doi: 10.1200/JCO.2005.02.9405. Epub 2005 Dec 19.