 Monohydrate Chemical Structure.png)
6-Mercaptopurine monohydrate (6-MP; NSC 755; 6 MP; NSC755; 6MP; NSC-755; Purinethol), the hydrated form of 6-Mercaptopurine, is an approved anticancer and immunosuppressive drug used for the treatment of ALL-acute lymphocytic leukemia, CML-chronic myeloid leukemia, Crohn's disease, and ulcerative colitis. Thiopurine methyltransferase metabolites are incorporated into DNA and RNA, inhibiting de novo purine synthesis.
Physicochemical Properties
| Molecular Formula | C5H6N4OS | |
| Molecular Weight | 170.19 | |
| Exact Mass | 170.026 | |
| Elemental Analysis | C, 35.29; H, 3.55; N, 32.92; O, 9.40; S, 18.84 | |
| CAS # | 6112-76-1 | |
| Related CAS # | 50-44-2 | |
| PubChem CID | 2724350 | |
| Appearance | Light yellow to yellow solid powder | |
| Boiling Point | 490.6ºC at 760 mmHg | |
| Melting Point | >300 °C(lit.) | |
| Flash Point | 250.5ºC | |
| LogP | 0.951 | |
| Hydrogen Bond Donor Count | 3 | |
| Hydrogen Bond Acceptor Count | 3 | |
| Rotatable Bond Count | 0 | |
| Heavy Atom Count | 11 | |
| Complexity | 190 | |
| Defined Atom Stereocenter Count | 0 | |
| SMILES | S=C1C2=C(N=C([H])N2[H])N([H])C([H])=N1.O([H])[H] |
|
| InChi Key | WFFQYWAAEWLHJC-UHFFFAOYSA-N | |
| InChi Code | InChI=1S/C5H4N4S.H2O/c10-5-3-4(7-1-6-3)8-2-9-5;/h1-2H,(H2,6,7,8,9,10);1H2 | |
| Chemical Name | 3,7-dihydropurine-6-thione;hydrate | |
| Synonyms |
|
|
| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
|
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | endogenous purines | |
| ln Vitro |
|
|
| ln Vivo |
|
|
| Enzyme Assay | L6 myotubes are incubated for 24 hours in either DMSO control or 6-Mercaptopurine hydrate (6-MP), with treatments in serum-free DMEM during the last 3 hours. They are then incubated for an additional 60 minutes at 37°C in the presence or absence of 100 nM insulin. Subsequently, 50 μg of protein lysates are gathered, put through SDS-PAGE, and then immunoblotted using primary antibodies for an entire night at 4°C. Using Image J software, densitometric analysis of scanned films is used to finally quantify the proteins[2]. | |
| Cell Assay | The Cell Viability Assay is used to quantify cell viability. 10,000 L6 skeletal muscle cells are seeded per well in 96-well plates, and after 7 days, the cells differentiate into myotubes. Before the assay, cells are treated for 24 hours with varying doses of 6-Mercaptopurine hydrate (6-MP). After 30 minutes of room temperature equilibration, 50 μL of Cell Titer-Glo reagent is added to each well, and the plates are mixed for 12 minutes on an orbital shaker to analyze the viability of the cells. A luminometer is used to measure luminosity[2]. | |
| Animal Protocol |
|
|
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation In the treatment of conditions such as ulcerative colitis and Crohn's disease, most professional guidelines and other experts consider breastfeeding to be acceptable during mercaptopurine therapy.[1-9] Azathioprine is rapidly converted to mercaptopurine, so data from mothers taking azathioprine apply to mercaptopurine. No active metabolites of mercaptopurine were found in the blood of breastfed infants whose mothers were taking azathioprine and only poorly documented cases of mild, asymptomatic neutropenia and increased rates of infection have been reported occasionally. It might be desirable to monitor exclusively breastfed infants with a complete blood count with differential, and liver function tests if azathioprine is used during lactation, although some authors feel that such monitoring is unnecessary.[10]. See the Azathioprine record for details. Mothers with decreased activity of the enzyme that detoxifies mercaptopurine metabolites may transmit higher levels of drug to their infants in breastmilk. It might be desirable to monitor exclusively breastfed infants with a complete blood count with differential, and liver function tests if mercaptopurine is used during lactation, although some authors feel that monitoring is unnecessary.[11] Avoiding breastfeeding for 4 hours after a dose should markedly decrease the dose received by the infant in breastmilk.[12] Most sources consider breastfeeding to be contraindicated during maternal antineoplastic drug therapy, although antimetabolites such as mercaptopurine appear to pose the least risk to breastfed infants.[13] After high-dose chemotherapy, it might be possible to breastfeed safely during intermittent therapy with an appropriate period of breastfeeding abstinence. Although no data are available to determine an appropriate period to withhold breastfeeding, the drug's terminal half-life suggests that withholding breastfeeding for 1 to 2 days may be sufficient. Chemotherapy may adversely affect the normal microbiome and chemical makeup of breastmilk.[14] ◉ Effects in Breastfed Infants In The Netherlands, 30 infants of mothers taking either azathioprine (n = 28) or mercaptopurine (n = 2) for inflammatory bowel disease during pregnancy and postpartum were followed at 1 to 6 years of age using a 43-item quality of life questionnaire. Of this cohort, 9 infants were breastfed for a mean of 7 months (range 3 to 13 months) No statistically significant differences were found between breastfed and formula-fed infants in any of the 12 domains of the survey.[19] In a multi-center study of women with inflammatory bowel disease in pregnancy (the PIANO registry), 102 women received a thiopurine (azathioprine or mercaptopurine) and another 67 received a thiopurine plus a biological agent (adalimumab, certolizumab, golimumab, infliximab, natalizumab, or ustekinumab) while breastfeeding their infants. Among those who received a thiopurine or combination therapy while breastfeeding, infant growth, development or infection rate was no different from 208 breastfed infants whose mothers received no treatment.[20] A national survey of gastroenterologists in Australia identified 21 infants who were breastfed by mothers taking a combination of allopurinol and a thiopurine (e.g. azathioprine, mercaptopurine) to treat inflammatory bowel disease. All had taken the combination during pregnancy also. Two postpartum infant deaths occurred, both at 3 months of age. One was a twin (premature birth-related) and the other from SIDS. The authors did not believe the deaths were medication related.[21] No information was provided on the extent of breastfeeding, drug dosages or the outcomes of the other infants. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. |
|
| References |
[1]. Clinical pharmacology and pharmacogenetics of thiopurines. Eur J Clin Pharmacol. 2008 Aug;64(8):753-67. [2]. 6-Mercaptopurine augments glucose transport activity in skeletal muscle cells in part via a mechanism dependent upon orphan nuclear receptor NR4A3. Am J Physiol Endocrinol Metab. 2013 Nov 1;305(9):E1081-92. [3]. 6-Mercaptopurine (6-MP) induces cell cycle arrest and apoptosis of neural progenitor cells in the developing fetal rat brain. Neurotoxicol Teratol. 2009 Mar-Apr;31(2):104-9. |
|
| Additional Infomation |
6-mercaptopurine monohydrate is an odorless light yellow to yellow crystalline powder. Becomes anhydrous at 284 °F. (NTP, 1992) Mercaptopurine hydrate is a hydrate. It contains a mercaptopurine. Mercaptopurine is a thiopurine-derivative antimetabolite with antineoplastic and immunosuppressive activities. Produced through the metabolism of mercaptopurine by hypoxanthine-guanine phosphoribosyltransferase (HGPRT), mercaptopurine metabolites 6-thioguanosine-5'-phosphate (6-thioGMP) and 6-thioinosine monophosphate (T-IMP) inhibit nucleotide interconversions and de novo purine synthesis, thereby blocking the formation of purine nucleotides and inhibiting DNA synthesis. This agent is also incorporated into DNA in the form of deoxythioguanosine, which results in the disruption of DNA replication. In addition, mercaptopurine is converted to 6-methylmercaptopurine ribonucleoside (MMPR) by 6-thiopurine methyltransferase; MMPRs are also potent inhibitors of de novo purine synthesis. (NCI04) An antimetabolite antineoplastic agent with immunosuppressant properties. It interferes with nucleic acid synthesis by inhibiting purine metabolism and is used, usually in combination with other drugs, in the treatment of or in remission maintenance programs for leukemia. See also: Mercaptopurine (annotation moved to). Drug Indication Xaluprine is indicated for the treatment of acute lymphoblastic leukaemia (ALL) in adults, adolescents and children. |
Solubility Data
| Solubility (In Vitro) |
|
|||
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (14.69 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.8758 mL | 29.3789 mL | 58.7579 mL | |
| 5 mM | 1.1752 mL | 5.8758 mL | 11.7516 mL | |
| 10 mM | 0.5876 mL | 2.9379 mL | 5.8758 mL |