WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 318596
CAS#: 58-14-0 (free base)
Description: Pyrimethamine is an antiprotozoal agent that inhibits the protozoal enzyme dihydrofolate reductase. Pyrimethamine prevents the production of tetrahydrofolic acid, an essential coenzyme involved in DNA and RNA synthesis. Pyrimethamine is a dihydrofolate reductase inhibitor antimalarial. The mechanism of action of pyrimethamine is as a Dihydrofolate Reductase Inhibitor. Pyrimethamine has also been found to limit the expression of the superoxide dismutase 1 gene, a protein involved in amyotrophic lateral sclerosis.
MedKoo Cat#: 318596
Name: Pyrimethamine
CAS#: 58-14-0 (free base)
Chemical Formula: C12H13ClN4
Exact Mass: 248.08287
Molecular Weight: 248.71
Elemental Analysis: C, 57.95; H, 5.27; Cl, 14.25; N, 22.53
Related CAS #: 7681-25-6 (phosphate) 58-14-0 (free base) 14720-95-7 (isethionate) 19085-09-7 (HCl) 53640-38-3 (sulfate)
Synonym: Pyrimethamine; BW 50-63; BW-50-63; BW50-63; Khloridin; Malocid; Malocide; NCI-C01683; NSC 3061; Pirimecidan; Pirimetamin; RP 4753; Tindurin; WR 297
IUPAC/Chemical Name: 5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine
InChi Key: WKSAUQYGYAYLPV-UHFFFAOYSA-N
InChi Code: InChI=1S/C12H13ClN4/c1-2-9-10(11(14)17-12(15)16-9)7-3-5-8(13)6-4-7/h3-6H,2H2,1H3,(H4,14,15,16,17)
SMILES Code: CCC1=C(C(=NC(=N1)N)N)C2=CC=C(C=C2)Cl
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | Pyrimethamine(RP4753) interferes with tetrahydrofolic acid synthesis from folic acid by inhibiting the enzyme dihydrofolate reductase (DHFR) with an IC50 value of 15.4 nM |
| In vitro activity: | Pyrimethamine inhibits RABV infection for 50% at 3.72 μM (EC50) with a 50% of toxicity (CC50) value of 11.1 μM (Fig. 1). Pyrimethamine is a diaminopyridine derivative that inhibits the dihydrofolate reductase (DHFR) and blocks de novo purine synthesis. For all viruses tested, pyrimethamine alone inhibited the viral replication with EC50 values < 2 μM (Fig. 3A). The capacity of pryrimethamine to inhibit the expression of IFN-inducible genes was further investigated in vitro. To this aim, STING-37 cells stably transfected with ISRE-luciferase reporter gene (Lucas-Hourani et al., 2013) were treated with or without different concentrations of pyrimethamine. No significant difference was observed suggesting that pyrimethamine does not induce the expression of ISREdependent genes (Fig. 6A). Pyrimethamine did not cause toxicity in this assay except at the highest concentration (80 μM) (Fig. 6B). More interestingly, in cells treated with human recombinant IFNα, the ISRE-luciferase expression is significantly decreased in the presence of pyrimethamine compared to DMSO-treated cells (negative controls) and this inhibition was still observed with the higher dose (1000 UI/mL) of IFNα (p < 0.01) (Fig. 6C). Reference: Antiviral Res. 2019 Jan;161:1-9. https://pubmed.ncbi.nlm.nih.gov/30367894/ |
| In vivo activity: | It was explored whether Pyrimethamine could inhibit tumorigenicity in vivo. To clarify the effect of pyrimethamine on tumor growth, a xenograft tumor assay was carried out in nude mice. PC3 cells (6 × 106) were implanted subcutaneously into the right armpit region of each nude mouse. When the tumor volume reached approximately 120 mm3, the mice were randomly divided into two groups and were orally administered either pyrimethamine (15 mg/kg) or vehicle control, once daily. After 30 days of treatment, it was found that tumor growth was suppressed in the pyrimethamine-treated group compared to that in the control group (P < 0.001) (Figures 3A, C). However, the body weights of mice showed no significant difference between the two groups (P >0.05). Moreover, the behavior, overall activity, and feeding pattern of mice did not display any obvious changes. To further identify the inhibitory effect of pyrimethamine on tumor growth, an immunohistochemical analysis was performed to detect the expression of Ki-67 and pp38 in paraffin-embedded mice tumors. It was found that the expression of Ki-67 and pp38 in the pyrimethamine-treated group was lower than that in the control group. The above results suggested that pyrimethamine significantly suppressed tumor growth in the xenograft model of nude mice by exhibiting favorable toxicological profiles. Reference: Front Pharmacol. 2020; 11: 758. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261869/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 10.0 | 40.2 |
The following data is based on the product molecular weight 248.71 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Rogée S, Larrous F, Jochmans D, Ben-Khalifa Y, Neyts J, Bourhy H. Pyrimethamine inhibits rabies virus replication in vitro. Antiviral Res. 2019 Jan;161:1-9. doi: 10.1016/j.antiviral.2018.10.016. Epub 2018 Oct 25. PMID: 30367894. 2. Zhou X, Zhang J, Hu X, He P, Guo J, Li J, Lan T, Liu J, Peng L, Li H. Pyrimethamine Elicits Antitumor Effects on Prostate Cancer by Inhibiting the p38-NF-κB Pathway. Front Pharmacol. 2020 May 25;11:758. doi: 10.3389/fphar.2020.00758. PMID: 32523533; PMCID: PMC7261869. |
| In vitro protocol: | 1. Rogée S, Larrous F, Jochmans D, Ben-Khalifa Y, Neyts J, Bourhy H. Pyrimethamine inhibits rabies virus replication in vitro. Antiviral Res. 2019 Jan;161:1-9. doi: 10.1016/j.antiviral.2018.10.016. Epub 2018 Oct 25. PMID: 30367894. 2. Zhou X, Zhang J, Hu X, He P, Guo J, Li J, Lan T, Liu J, Peng L, Li H. Pyrimethamine Elicits Antitumor Effects on Prostate Cancer by Inhibiting the p38-NF-κB Pathway. Front Pharmacol. 2020 May 25;11:758. doi: 10.3389/fphar.2020.00758. PMID: 32523533; PMCID: PMC7261869. 1. Rogée S, Larrous F, Jochmans D, Ben-Khalifa Y, Neyts J, Bourhy H. Pyrimethamine inhibits rabies virus replication in vitro. Antiviral Res. 2019 Jan;161:1-9. doi: 10.1016/j.antiviral.2018.10.016. Epub 2018 Oct 25. PMID: 30367894. 2. Zhou X, Zhang J, Hu X, He P, Guo J, Li J, Lan T, Liu J, Peng L, Li H. Pyrimethamine Elicits Antitumor Effects on Prostate Cancer by Inhibiting the p38-NF-κB Pathway. Front Pharmacol. 2020 May 25;11:758. doi: 10.3389/fphar.2020.00758. PMID: 32523533; PMCID: PMC7261869. |
| In vivo protocol: | 1. Rogée S, Larrous F, Jochmans D, Ben-Khalifa Y, Neyts J, Bourhy H. Pyrimethamine inhibits rabies virus replication in vitro. Antiviral Res. 2019 Jan;161:1-9. doi: 10.1016/j.antiviral.2018.10.016. Epub 2018 Oct 25. PMID: 30367894. 2. Zhou X, Zhang J, Hu X, He P, Guo J, Li J, Lan T, Liu J, Peng L, Li H. Pyrimethamine Elicits Antitumor Effects on Prostate Cancer by Inhibiting the p38-NF-κB Pathway. Front Pharmacol. 2020 May 25;11:758. doi: 10.3389/fphar.2020.00758. PMID: 32523533; PMCID: PMC7261869. |
1: Khuluza F, Kigera S, Jähnke RW, Heide L. Use of thin-layer chromatography to detect counterfeit sulfadoxine/pyrimethamine tablets with the wrong active ingredient in Malawi. Malar J. 2016 Apr 14;15(1):215. doi: 10.1186/s12936-016-1259-9. PubMed PMID: 27075749.
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3: Desai M, Gutman J, Taylor SM, Wiegand RE, Khairallah C, Kayentao K, Ouma P, Coulibaly SO, Kalilani L, Mace KE, Arinaitwe E, Mathanga DP, Doumbo O, Otieno K, Edgar D, Chaluluka E, Kamuliwo M, Ades V, Skarbinski J, Shi YP, Magnussen P, Meshnick S, Ter Kuile FO. Impact of Sulfadoxine-Pyrimethamine Resistance on Effectiveness of Intermittent Preventive Therapy for Malaria in Pregnancy at Clearing Infections and Preventing Low Birth Weight. Clin Infect Dis. 2016 Feb 1;62(3):323-33. doi: 10.1093/cid/civ881. Epub 2015 Oct 20. PubMed PMID: 26486699; PubMed Central PMCID: PMC4762476.
4: Awab GR, Imwong M, Pukrittayakamee S, Alim F, Hanpithakpong W, Tarning J, Dondorp AM, Day NP, White NJ, Woodrow CJ. Clinical trials of artesunate plus sulfadoxine-pyrimethamine for Plasmodium falciparum malaria in Afghanistan: maintained efficacy a decade after introduction. Malar J. 2016 Feb 25;15(1):121. doi: 10.1186/s12936-016-1167-z. PubMed PMID: 26917051; PubMed Central PMCID: PMC4766631.
5: Teil J, Dupont D, Charpiat B, Corvaisier S, Vial T, Leboucher G, Wallon M, Peyron F. Treatment of Congenital Toxoplasmosis: Safety of the Sulfadoxine-Pyrimethamine Combination in Children Based on a Method of Causality Assessment. Pediatr Infect Dis J. 2016 Feb 19. [Epub ahead of print] PubMed PMID: 26906163.
