Identification
- Summary
Arsenic trioxide is a chemotherapeutic agent used in the treatment of refractory or relapsed acute promyelocytic leukemia in patients with prior retinoid and anthracycline chemotherapy.
- Brand Names
- Trisenox
- Generic Name
- Arsenic trioxide
- DrugBank Accession Number
- DB01169
- Background
Arsenic trioxide is a chemotherapeutic agent of idiopathic function used to treat leukemia that is unresponsive to first line agents. It is suspected that arsenic trisulfide induces cancer cells to undergo apoptosis. In general, arsenic is known to be a naturally toxic substance capable of eliciting a variety of dangerous adverse effects. The enzyme thioredoxin reductase has recently been identified as a target for arsenic trioxide.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Arsenic trioxide (DB01169)
- Weight
- Average: 197.84
Monoisotopic: 197.827934 - Chemical Formula
- As2O3
- Synonyms
- Acide Arsenieux
- Anhydride Arsenieux
- Arsenic Blanc
- Arsenic oxide
- Arsenic trioxide
- Arsenic(III) oxide
- arsénico trióxido
- Arsenigen Saure
- Arsenolite
- Arsenous oxide
- Arsenous oxide anhydride
- Diarsenic oxide
- Diarsenic trioxide
- White arsenic
Pharmacology
- Indication
For induction of remission and consolidation in patients with acute promyelocytic leukemia (APL), and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Acute promyelocytic leukemia (apl) Regimen in combination with: Tretinoin (DB00755) •••••••••••• ••••• ••••••••• Used in combination to treat Acute promyelocytic leukemia (apl) Regimen in combination with: Tretinoin (DB00755) •••••••••••• ••••• •••••••••• •••••••• ••••••••••••• Treatment of Refractory acute promyelocytic leukemia •••••••••••• •••••••• ••••••••••••• Treatment of Refractory acute promyelocytic leukemia •••••••••••• Treatment of Relapsed acute promyelocytic leukemia •••••••••••• •••••••• ••••••••••••• - Contraindications & Blackbox Warnings
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Arsenic Trioxide is indicated for induction of remission and consolidation in patients with acute promyelocytic leukemia (APL) who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy.
- Mechanism of action
The mechanism of action of Arsenic Trioxide is not completely understood. Arsenic trioxide causes morphological changes and DNA fragmentation characteristic of apoptosis in NB4 human promyelocytic leukemia cells in vitro. Arsenic trioxide also causes damage or degradation of the fusion protein PML/RAR-alpha. It is suspected that arsenic trioxide induces cancer cells to undergo apoptosis.
Target Actions Organism AInhibitor of nuclear factor kappa-B kinase subunit beta inducerHumans AThioredoxin reductase 1, cytoplasmic inhibitorHumans ATranscription factor AP-1 inducerHumans AG1/S-specific cyclin-D1 antagonistHumans AMitogen-activated protein kinase 3 inducerHumans AMitogen-activated protein kinase 1 inducerHumans URAC-alpha serine/threonine-protein kinase inducerHumans UCyclin-dependent kinase inhibitor 1 Not Available Humans UHistone deacetylase 1 Not Available Humans UProtein PML Not Available Humans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
75% bound
- Metabolism
Inorganic, lyophilized arsenic trioxide, when placed in solution, is immediately hydrolyzed to arsenous acid - this appears to be the pharmacologically active species of arsenic trioxide.2 Further metabolism involves the oxidation of arsenous acid to arsenic acid, and an oxidative methylation of arsenous acid to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) by methyltransferases in the liver. Both MMA and DMA have relatively long half-lives and can accumulate following multiple doses, the extent of which depends upon the dosing regimen in question.2
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- Route of elimination
Trivalent arsenic is mostly methylated in humans and excreted in urine.
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Symptoms of overdose include convulsions, muscle weakness and confusion.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Arsenic trioxide which could result in a higher serum level. Abaloparatide The risk or severity of adverse effects can be increased when Arsenic trioxide is combined with Abaloparatide. Abatacept The risk or severity of adverse effects can be increased when Arsenic trioxide is combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Arsenic trioxide. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Arsenic trioxide. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Arsenic Trioxide Accord Injection, solution, concentrate 1 mg/ml Intravenous Accord Healthcare S.L.U. 2020-12-16 Not applicable EU 
Arsenic Trioxide Accord Injection, solution, concentrate 1 mg/ml Intravenous Accord Healthcare S.L.U. 2020-12-16 Not applicable EU Arsenic Trioxide Accord Injection, solution, concentrate 1 mg/ml Intravenous Accord Healthcare S.L.U. 2020-12-16 Not applicable EU Arsenic Trioxide for Injection Solution 10 mg / 10 mL Intravenous Sandoz Canada Incorporated 2022-03-11 Not applicable Canada 
Arsenic Trioxide for Injection Solution 2 mg / mL Intravenous Eugia Pharma Inc. Not applicable Not applicable Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Arsenic Trioxide Injection 1 mg/1mL Intravenous Nexus Pharmaceuticals Inc 2018-11-19 Not applicable US 
Arsenic Trioxide Injection 1 mg/1mL Intravenous Gland Pharma Limited 2022-04-22 Not applicable US Arsenic trioxide Injection, solution 2 mg/1mL Intravenous Zydus Lifesciences Limited 2019-09-03 Not applicable US Arsenic Trioxide Injection, solution 2 mg/1mL Intravenous AuroMedics Pharma LLC 2021-10-15 Not applicable US Arsenic trioxide Injection, solution 1 mg/1mL Intravenous Zydus Pharmaceuticals USA Inc. 2018-11-14 Not applicable US
Categories
- ATC Codes
- L01XX27 — Arsenic trioxide
- Drug Categories
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Arsenicals
- Cardiotoxic antineoplastic agents
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 Enzyme Inhibitors
- Drugs that are Mainly Renally Excreted
- Highest Risk QTc-Prolonging Agents
- Hyperglycemia-Associated Agents
- Hypotensive Agents
- Immunosuppressive Agents
- Myelosuppressive Agents
- Narrow Therapeutic Index Drugs
- Oxides
- Oxygen Compounds
- P-glycoprotein inhibitors
- QTc Prolonging Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of inorganic compounds known as metalloid oxides. These are inorganic compounds containing an oxygen atom of an oxidation state of -2, in which the heaviest atom bonded to the oxygen is a metalloid.
- Kingdom
- Inorganic compounds
- Super Class
- Mixed metal/non-metal compounds
- Class
- Metalloid organides
- Sub Class
- Metalloid oxides
- Direct Parent
- Metalloid oxides
- Alternative Parents
- Metalloid salts / Inorganic oxides / Inorganic arsenic compounds
- Substituents
- Inorganic arsenic compound / Inorganic metalloid salt / Inorganic oxide / Metalloid oxide
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- S7V92P67HO
- CAS number
- 1327-53-3
- InChI Key
- IKWTVSLWAPBBKU-UHFFFAOYSA-N
- InChI
- InChI=1S/As2O3/c3-1-5-2-4
- IUPAC Name
- diarsorosooxidane
- SMILES
- O=[As]O[As]=O
References
- General References
- External Links
- KEGG Drug
- D02106
- PubChem Compound
- 261004
- PubChem Substance
- 46506448
- ChemSpider
- 229103
- 18330
- ChEMBL
- CHEMBL1200978
- Therapeutic Targets Database
- DNC000255
- PharmGKB
- PA448486
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Arsenic_trioxide
- MSDS
- Download (78.3 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Treatment Acute Promyelocytic Leukemia 1 4 Completed Treatment Childhood Acute Promyelocytic Leukemia (M3) 1 4 Unknown Status Treatment Acute Promyelocytic Leukemia 1 4 Unknown Status Treatment Refractory Acute Promyelocytic Leukemia / Relapsed Acute Promyelocytic Leukemia 1 3 Active Not Recruiting Treatment Acute Promyelocytic Leukemia 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Akorn Inc.
- Cell Therapeutics Inc.
- Cephalon Inc.
- CP Pharmaceuticals Ltd.
- Spectrum Pharmaceuticals
- TTY Biopharm Co. Ltd.
- Dosage Forms
Form Route Strength Injection Intravenous 1 mg/1mL Injection Intravenous 2 mg/1mL Injection, solution Intravenous 1 mg/1mL Injection, solution Intravenous 2 mg/2mL Solution Intravenous 1 mg / mL Solution Intravenous 2 mg / mL Injection, solution, concentrate Intravenous Injection Intravenous Injection, solution, concentrate Intravenous 10 mg/10ml Injection, solution Intravenous 2 mg/ml Injection, solution, concentrate Intravenous 1 MG/ML Injection, solution Intravenous 2 mg/1mL Injection, solution, concentrate Intravenous 2 mg/ml Injection, solution, concentrate Intravenous; Parenteral 1 MG/ML Injection, solution, concentrate Intravenous; Parenteral 2 MG/ML Solution Intravenous 10 mg / 10 mL Solution Intravenous 12 mg / 6 mL Injection, solution, concentrate Intravenous 1 mg/1ml Solution Intravenous 1.000 mg Solution Intravenous 1 mg/1ml - Prices
Unit description Cost Unit Trisenox 10 mg/10 ml ampule 43.58USD ml Arsenic trioxide powder 2.59USD g DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6723351 No 2004-04-20 2018-11-10 US US6855339 No 2005-02-15 2018-11-10 US US6861076 No 2005-03-01 2018-11-10 US US6884439 No 2005-04-26 2018-11-10 US US6982096 No 2006-01-03 2018-11-10 US US8273379 No 2012-09-25 2018-11-10 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility 1.7E+004 mg/L (at 16 °C) SHIU,WY ET AL. (1990) - Predicted Properties
Property Value Source logP 1.07 Chemaxon pKa (Strongest Basic) -6 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 43.37 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 4.24 m3·mol-1 Chemaxon Polarizability 6.91 Å3 Chemaxon Number of Rings 0 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9839 Blood Brain Barrier + 0.9549 Caco-2 permeable - 0.526 P-glycoprotein substrate Non-substrate 0.8227 P-glycoprotein inhibitor I Non-inhibitor 0.9138 P-glycoprotein inhibitor II Non-inhibitor 0.9925 Renal organic cation transporter Non-inhibitor 0.9297 CYP450 2C9 substrate Non-substrate 0.9036 CYP450 2D6 substrate Non-substrate 0.829 CYP450 3A4 substrate Non-substrate 0.7462 CYP450 1A2 substrate Non-inhibitor 0.7393 CYP450 2C9 inhibitor Non-inhibitor 0.8625 CYP450 2D6 inhibitor Non-inhibitor 0.9133 CYP450 2C19 inhibitor Non-inhibitor 0.7968 CYP450 3A4 inhibitor Non-inhibitor 0.9567 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9743 Ames test Non AMES toxic 0.5978 Carcinogenicity Non-carcinogens 0.5984 Biodegradation Ready biodegradable 0.8156 Rat acute toxicity 2.5942 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8253 hERG inhibition (predictor II) Non-inhibitor 0.9812
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inducer
- General Function
- Scaffold protein binding
- Specific Function
- Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or oth...
- Gene Name
- IKBKB
- Uniprot ID
- O14920
- Uniprot Name
- Inhibitor of nuclear factor kappa-B kinase subunit beta
- Molecular Weight
- 86563.245 Da
References
- Ouyang W, Ma Q, Li J, Zhang D, Liu ZG, Rustgi AK, Huang C: Cyclin D1 induction through IkappaB kinase beta/nuclear factor-kappaB pathway is responsible for arsenite-induced increased cell cycle G1-S phase transition in human keratinocytes. Cancer Res. 2005 Oct 15;65(20):9287-93. [Article]
- Ouyang W, Li J, Ma Q, Huang C: Essential roles of PI-3K/Akt/IKKbeta/NFkappaB pathway in cyclin D1 induction by arsenite in JB6 Cl41 cells. Carcinogenesis. 2006 Apr;27(4):864-73. Epub 2005 Dec 29. [Article]
- Ouyang W, Zhang D, Ma Q, Li J, Huang C: Cyclooxygenase-2 induction by arsenite through the IKKbeta/NFkappaB pathway exerts an antiapoptotic effect in mouse epidermal Cl41 cells. Environ Health Perspect. 2007 Apr;115(4):513-8. Epub 2006 Dec 14. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Thioredoxin-disulfide reductase activity
- Specific Function
- Isoform 1 may possess glutaredoxin activity as well as thioredoxin reductase activity and induces actin and tubulin polymerization, leading to formation of cell membrane protrusions. Isoform 4 enha...
- Gene Name
- TXNRD1
- Uniprot ID
- Q16881
- Uniprot Name
- Thioredoxin reductase 1, cytoplasmic
- Molecular Weight
- 70905.58 Da
References
- Lu J, Chew EH, Holmgren A: Targeting thioredoxin reductase is a basis for cancer therapy by arsenic trioxide. Proc Natl Acad Sci U S A. 2007 Jul 24;104(30):12288-93. Epub 2007 Jul 18. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inducer
- General Function
- Transcriptional activator activity, rna polymerase ii transcription factor binding
- Specific Function
- Transcription factor that recognizes and binds to the enhancer heptamer motif 5'-TGA[CG]TCA-3'. Promotes activity of NR5A1 when phosphorylated by HIPK3 leading to increased steroidogenic gene expre...
- Gene Name
- JUN
- Uniprot ID
- P05412
- Uniprot Name
- Transcription factor AP-1
- Molecular Weight
- 35675.32 Da
References
- Muscarella DE, Bloom SE: Differential activation of the c-Jun N-terminal kinase pathway in arsenite-induced apoptosis and sensitization of chemically resistant compared to susceptible B-lymphoma cell lines. Toxicol Sci. 2002 Jul;68(1):82-92. [Article]
- Dong Z: The molecular mechanisms of arsenic-induced cell transformation and apoptosis. Environ Health Perspect. 2002 Oct;110 Suppl 5:757-9. [Article]
- Drobna Z, Jaspers I, Thomas DJ, Styblo M: Differential activation of AP-1 in human bladder epithelial cells by inorganic and methylated arsenicals. FASEB J. 2003 Jan;17(1):67-9. Epub 2002 Nov 15. [Article]
- Li J, Gorospe M, Barnes J, Liu Y: Tumor promoter arsenite stimulates histone H3 phosphoacetylation of proto-oncogenes c-fos and c-jun chromatin in human diploid fibroblasts. J Biol Chem. 2003 Apr 11;278(15):13183-91. Epub 2003 Jan 23. [Article]
- Kietzmann T, Samoylenko A, Immenschuh S: Transcriptional regulation of heme oxygenase-1 gene expression by MAP kinases of the JNK and p38 pathways in primary cultures of rat hepatocytes. J Biol Chem. 2003 May 16;278(20):17927-36. Epub 2003 Mar 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Transcription factor binding
- Specific Function
- Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S t...
- Gene Name
- CCND1
- Uniprot ID
- P24385
- Uniprot Name
- G1/S-specific cyclin-D1
- Molecular Weight
- 33728.74 Da
References
- Hyun Park W, Hee Cho Y, Won Jung C, Oh Park J, Kim K, Hyuck Im Y, Lee MH, Ki Kang W, Park K: Arsenic trioxide inhibits the growth of A498 renal cell carcinoma cells via cell cycle arrest or apoptosis. Biochem Biophys Res Commun. 2003 Jan 3;300(1):230-5. [Article]
- Ouyang W, Ma Q, Li J, Zhang D, Liu ZG, Rustgi AK, Huang C: Cyclin D1 induction through IkappaB kinase beta/nuclear factor-kappaB pathway is responsible for arsenite-induced increased cell cycle G1-S phase transition in human keratinocytes. Cancer Res. 2005 Oct 15;65(20):9287-93. [Article]
- Ouyang W, Li J, Ma Q, Huang C: Essential roles of PI-3K/Akt/IKKbeta/NFkappaB pathway in cyclin D1 induction by arsenite in JB6 Cl41 cells. Carcinogenesis. 2006 Apr;27(4):864-73. Epub 2005 Dec 29. [Article]
- Hwang BJ, Utti C, Steinberg M: Induction of cyclin D1 by submicromolar concentrations of arsenite in human epidermal keratinocytes. Toxicol Appl Pharmacol. 2006 Dec 1;217(2):161-7. Epub 2006 Aug 11. [Article]
- Ouyang W, Li J, Zhang D, Jiang BH, Huang DC: PI-3K/Akt signal pathway plays a crucial role in arsenite-induced cell proliferation of human keratinocytes through induction of cyclin D1. J Cell Biochem. 2007 Jul 1;101(4):969-78. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inducer
- General Function
- Phosphatase binding
- Specific Function
- Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK ca...
- Gene Name
- MAPK3
- Uniprot ID
- P27361
- Uniprot Name
- Mitogen-activated protein kinase 3
- Molecular Weight
- 43135.16 Da
References
- Fauconneau B, Petegnief V, Sanfeliu C, Piriou A, Planas AM: Induction of heat shock proteins (HSPs) by sodium arsenite in cultured astrocytes and reduction of hydrogen peroxide-induced cell death. J Neurochem. 2002 Dec;83(6):1338-48. [Article]
- Jung DK, Bae GU, Kim YK, Han SH, Choi WS, Kang H, Seo DW, Lee HY, Cho EJ, Lee HW, Han JW: Hydrogen peroxide mediates arsenite activation of p70(s6k) and extracellular signal-regulated kinase. Exp Cell Res. 2003 Oct 15;290(1):144-54. [Article]
- Tanaka-Kagawa T, Hanioka N, Yoshida H, Jinno H, Ando M: Arsenite and arsenate activate extracellular signal-regulated kinases 1/2 by an epidermal growth factor receptor-mediated pathway in normal human keratinocytes. Br J Dermatol. 2003 Dec;149(6):1116-27. [Article]
- Felix K, Manna SK, Wise K, Barr J, Ramesh GT: Low levels of arsenite activates nuclear factor-kappaB and activator protein-1 in immortalized mesencephalic cells. J Biochem Mol Toxicol. 2005;19(2):67-77. [Article]
- Mousa SA, O'Connor L, Rossman TG, Block E: Pro-angiogenesis action of arsenic and its reversal by selenium-derived compounds. Carcinogenesis. 2007 May;28(5):962-7. Epub 2006 Dec 8. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inducer
- General Function
- Rna polymerase ii carboxy-terminal domain kinase activity
- Specific Function
- Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK ca...
- Gene Name
- MAPK1
- Uniprot ID
- P28482
- Uniprot Name
- Mitogen-activated protein kinase 1
- Molecular Weight
- 41389.265 Da
References
- Dong Z: The molecular mechanisms of arsenic-induced cell transformation and apoptosis. Environ Health Perspect. 2002 Oct;110 Suppl 5:757-9. [Article]
- He Z, Ma WY, Liu G, Zhang Y, Bode AM, Dong Z: Arsenite-induced phosphorylation of histone H3 at serine 10 is mediated by Akt1, extracellular signal-regulated kinase 2, and p90 ribosomal S6 kinase 2 but not mitogen- and stress-activated protein kinase 1. J Biol Chem. 2003 Mar 21;278(12):10588-93. Epub 2003 Jan 14. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- Protein serine/threonine/tyrosine kinase activity
- Specific Function
- AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, ...
- Gene Name
- AKT1
- Uniprot ID
- P31749
- Uniprot Name
- RAC-alpha serine/threonine-protein kinase
- Molecular Weight
- 55686.035 Da
References
- Fauconneau B, Petegnief V, Sanfeliu C, Piriou A, Planas AM: Induction of heat shock proteins (HSPs) by sodium arsenite in cultured astrocytes and reduction of hydrogen peroxide-induced cell death. J Neurochem. 2002 Dec;83(6):1338-48. [Article]
- He Z, Ma WY, Liu G, Zhang Y, Bode AM, Dong Z: Arsenite-induced phosphorylation of histone H3 at serine 10 is mediated by Akt1, extracellular signal-regulated kinase 2, and p90 ribosomal S6 kinase 2 but not mitogen- and stress-activated protein kinase 1. J Biol Chem. 2003 Mar 21;278(12):10588-93. Epub 2003 Jan 14. [Article]
- Ivanov VN, Hei TK: Combined treatment with EGFR inhibitors and arsenite upregulated apoptosis in human EGFR-positive melanomas: a role of suppression of the PI3K-AKT pathway. Oncogene. 2005 Jan 20;24(4):616-26. [Article]
- Wang ZX, Jiang CS, Liu L, Wang XH, Jin HJ, Wu Q, Chen Q: The role of Akt on arsenic trioxide suppression of 3T3-L1 preadipocyte differentiation. Cell Res. 2005 May;15(5):379-86. [Article]
- Tsou TC, Tsai FY, Hsieh YW, Li LA, Yeh SC, Chang LW: Arsenite induces endothelial cytotoxicity by down-regulation of vascular endothelial nitric oxide synthase. Toxicol Appl Pharmacol. 2005 Nov 1;208(3):277-84. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- May be involved in p53/TP53 mediated inhibition of cellular proliferation in response to DNA damage. Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localization and assembly of cyclin D-CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex. Inhibits DNA synthesis by DNA polymerase delta by competing with POLD3 for PCNA binding (PubMed:11595739).
- Specific Function
- Cyclin binding
- Gene Name
- CDKN1A
- Uniprot ID
- P38936
- Uniprot Name
- Cyclin-dependent kinase inhibitor 1
- Molecular Weight
- 18119.145 Da
References
- Huang HS, Liu ZM, Hong DY: Blockage of JNK pathway enhances arsenic trioxide-induced apoptosis in human keratinocytes. Toxicol Appl Pharmacol. 2010 Apr 15;244(2):234-41. doi: 10.1016/j.taap.2009.12.037. Epub 2010 Jan 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Transcription regulatory region sequence-specific dna binding
- Specific Function
- Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an impo...
- Gene Name
- HDAC1
- Uniprot ID
- Q13547
- Uniprot Name
- Histone deacetylase 1
- Molecular Weight
- 55102.615 Da
References
- Huang HS, Liu ZM, Hong DY: Blockage of JNK pathway enhances arsenic trioxide-induced apoptosis in human keratinocytes. Toxicol Appl Pharmacol. 2010 Apr 15;244(2):234-41. doi: 10.1016/j.taap.2009.12.037. Epub 2010 Jan 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Functions via its association with PML-nuclear bodies (PML-NBs) in a wide range of important cellular processes, including tumor suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechanisms. Acts as the scaffold of PML-NBs allowing other proteins to shuttle in and out, a process which is regulated by SUMO-mediated modifications and interactions. Isoform PML-4 has a multifaceted role in the regulation of apoptosis and growth suppression: activates RB1 and inhibits AKT1 via interactions with PP1 and PP2A phosphatases respectively, negatively affects the PI3K pathway by inhibiting MTOR and activating PTEN, and positively regulates p53/TP53 by acting at different levels (by promoting its acetylation and phosphorylation and by inhibiting its MDM2-dependent degradation). Isoform PML-4 also: acts as a transcriptional repressor of TBX2 during cellular senescence and the repression is dependent on a functional RBL2/E2F4 repressor complex, regulates double-strand break repair in gamma-irradiation-induced DNA damage responses via its interaction with WRN, acts as a negative regulator of telomerase by interacting with TERT, and regulates PER2 nuclear localization and circadian function. Isoform PML-6 inhibits specifically the activity of the tetrameric form of PKM. The nuclear isoforms (isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4 and isoform PML-5) in concert with SATB1 are involved in local chromatin-loop remodeling and gene expression regulation at the MHC-I locus. Isoform PML-2 is required for efficient IFN-gamma induced MHC II gene transcription via regulation of CIITA. Cytoplasmic PML is involved in the regulation of the TGF-beta signaling pathway. PML also regulates transcription activity of ELF4 and can act as an important mediator for TNF-alpha- and IFN-alpha-mediated inhibition of endothelial cell network formation and migration.
- Specific Function
- Cobalt ion binding
- Gene Name
- PML
- Uniprot ID
- P29590
- Uniprot Name
- Protein PML
- Molecular Weight
- 97549.475 Da
References
- Zhang XW, Yan XJ, Zhou ZR, Yang FF, Wu ZY, Sun HB, Liang WX, Song AX, Lallemand-Breitenbach V, Jeanne M, Zhang QY, Yang HY, Huang QH, Zhou GB, Tong JH, Zhang Y, Wu JH, Hu HY, de The H, Chen SJ, Chen Z: Arsenic trioxide controls the fate of the PML-RARalpha oncoprotein by directly binding PML. Science. 2010 Apr 9;328(5975):240-3. doi: 10.1126/science.1183424. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Noreault TL, Kostrubsky VE, Wood SG, Nichols RC, Strom SC, Trask HW, Wrighton SA, Evans RM, Jacobs JM, Sinclair PR, Sinclair JF: Arsenite decreases CYP3A4 and RXRalpha in primary human hepatocytes. Drug Metab Dispos. 2005 Jul;33(7):993-1003. Epub 2005 Apr 15. [Article]
- Mann KK, Padovani AM, Guo Q, Colosimo AL, Lee HY, Kurie JM, Miller WH Jr: Arsenic trioxide inhibits nuclear receptor function via SEK1/JNK-mediated RXRalpha phosphorylation. J Clin Invest. 2005 Oct;115(10):2924-33. Epub 2005 Sep 22. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Toxic substance binding
- Specific Function
- Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Serum albumin
- Molecular Weight
- 69365.94 Da
References
- Shooshtary S, Behtash S, Nafisi S: Arsenic trioxide binding to serum proteins. J Photochem Photobiol B. 2015 Jul;148:31-36. doi: 10.1016/j.jphotobiol.2015.03.001. Epub 2015 Apr 1. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- Organic anion transmembrane transporter activity
- Specific Function
- Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
- Gene Name
- ABCC2
- Uniprot ID
- Q92887
- Uniprot Name
- Canalicular multispecific organic anion transporter 1
- Molecular Weight
- 174205.64 Da
References
- Kauffmann HM, Pfannschmidt S, Zoller H, Benz A, Vorderstemann B, Webster JI, Schrenk D: Influence of redox-active compounds and PXR-activators on human MRP1 and MRP2 gene expression. Toxicology. 2002 Feb 28;171(2-3):137-46. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- Hu XM, Hirano T, Oka K: Arsenic trioxide induces apoptosis equally in T lymphoblastoid leukemia MOLT-4 cells and P-gp-expressing daunorubicin-resistant MOLT-4 cells. Cancer Chemother Pharmacol. 2003 Feb;51(2):119-26. Epub 2002 Nov 20. [Article]
- Wei HL, Yao XJ, Li YN, Wang P, Zhao HS, Bai DC, Peng X, Ma LF: [Arsenic trioxide inhibits P-glycoprotein expression in multidrug-resistant human leukemia K562/ADM cell line that overexpresses mdr-1 gene and enhances their chemotherapeutic sensitivity]. Zhonghua Xue Ye Xue Za Zhi. 2003 Jan;24(1):28-31. [Article]
- Wei H, Su H, Bai D, Zhao H, Ge J, Wang B, Yao X, Ma L: Arsenic trioxide inhibits p-glycoprotein expression in multidrug-resistant human leukemia cells that overexpress the MDR1 gene. Chin Med J (Engl). 2003 Nov;116(11):1644-8. [Article]
- Kimura A, Ishida Y, Wada T, Yokoyama H, Mukaida N, Kondo T: MRP-1 expression levels determine strain-specific susceptibility to sodium arsenic-induced renal injury between C57BL/6 and BALB/c mice. Toxicol Appl Pharmacol. 2005 Feb 15;203(1):53-61. [Article]
- Cronin CJ, Mendel JE, Mukhtar S, Kim YM, Stirbl RC, Bruck J, Sternberg PW: An automated system for measuring parameters of nematode sinusoidal movement. BMC Genet. 2005 Feb 7;6:5. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:54