Pafuramidine | DB-289 | CAS#186953-56-0 | 837369-26-3 | antimalarial

Pafuramidine
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 326798

CAS#: 186953-56-0

Description: Pafuramidine, also known as DB289, is an orally bioavailable prodrug of furamidine (DB75) which was developed for the treatment of human African trypanosomiasis. Pafuramidine is less toxic than previous diamidines such as pentamidine. To date, human trials suggest that pafuramidine is well tolerated overall and has clinical activity against Pneumocystis pneumonia. DB289 is a promising new antimalarial compound that could become an important component of new antimalarial combinations.

Chemical Structure

Pafuramidine

CAS# 186953-56-0

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 326798
Name: Pafuramidine
CAS#: 186953-56-0
Chemical Formula: C20H20N4O3
Exact Mass: 364.15
Molecular Weight: 364.405
Elemental Analysis: C, 65.92; H, 5.53; N, 15.38; O, 13.17

Price and Availability

Size	Price	Availability	Quantity
10mg	USD 500
50mg	USD 1050
100mg	USD 1640
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Related CAS #: 186953-56-0 837369-26-3 (maleate)

Synonym: DB289; DB-289; DB 289; Pafuramidine

IUPAC/Chemical Name: N'-methoxy-4-[5-[4-[(Z)-N'-methoxycarbamimidoyl]phenyl]furan-2-yl]benzenecarboximidamide

InChi Key: UKOQVLAXCBRRGH-UHFFFAOYSA-N

InChi Code: InChI=1S/C20H20N4O3/c1-25-23-19(21)15-7-3-13(4-8-15)17-11-12-18(27-17)14-5-9-16(10-6-14)20(22)24-26-2/h3-12H,1-2H3,(H2,21,23)(H2,22,24)

SMILES Code: N/C(C1=CC=C(C2=CC=C(C3=CC=C(/C(N)=N/OC)C=C3)O2)C=C1)=N\OC

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

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

More Info: Related CAS# 186953-56-0 (Pafuramidine) 837369-26-3 (Pafuramidine maleate)

Product Data:

Product Data

Instruction:

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Biological target:	Pafuramidine (DB289) is an orally active prodrug of Furamidine (HY-110137A). Pafuramidine is a potent anti-parasitic agent, can be used to research trypanosomiasis, Pneumocystis pneumonia and malaria.
In vitro activity:	In the guinea pig ventricular myocytes, treatment with furamidine, a PRMT1-specific inhibitor, prolonged the action potential duration (APD). This study further show that this APD prolongation was attributable to IKs reduction. In HEK293T cells expressing human KCNQ1 and KCNE1, inhibiting PRMT1 via furamidine reduced IKs and concurrently decreased the arginine methylation of KCNQ1, a pore-forming α-subunit. Reference: J Cell Physiol. 2022 Jul;237(7):3069-3079. https://pubmed.ncbi.nlm.nih.gov/35580065/
In vivo activity:	The efficacy of a novel orally administered prodrug, 2,5-bis(4-amidinophenyl)-furan-bis-O-methlylamidoxime (pafuramidine, DB289), was tested in the vervet monkey (Chlorocebus [Cercopithecus] aethiops) model of sleeping sickness. In the groups treated in the early stage, 10 mg/kg of pafuramidine completely cured all three monkeys, whereas lower doses of 3 mg/kg and 1 mg/kg cured only one of three and zero of three monkeys, respectively. Treatment of late-stage infections resulted in cure rates of one of three (group 4) and zero of three (group 5) monkeys. These studies demonstrated that pafuramidine was orally active in monkeys with early-stage T. brucei rhodesiense infections at dose rates above 3 mg/kg for 5 days. Reference: Antimicrob Agents Chemother. 2009 Mar;53(3):953-7. https://pubmed.ncbi.nlm.nih.gov/19064893/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMSO	33.3	91.46

Preparing Stock Solutions

The following data is based on the product molecular weight 364.41 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. An X, Lee J, Kim GH, Kim HJ, Pyo HJ, Kwon I, Cho H. Modulation of IKs channel-PIP2 interaction by PRMT1 plays a critical role in the control of cardiac repolarization. J Cell Physiol. 2022 Jul;237(7):3069-3079. doi: 10.1002/jcp.30775. Epub 2022 May 17. PMID: 35580065; PMCID: PMC9543859. 2. Jenquin JR, Coonrod LA, Silverglate QA, Pellitier NA, Hale MA, Xia G, Nakamori M, Berglund JA. Furamidine Rescues Myotonic Dystrophy Type I Associated Mis-Splicing through Multiple Mechanisms. ACS Chem Biol. 2018 Sep 21;13(9):2708-2718. doi: 10.1021/acschembio.8b00646. Epub 2018 Aug 27. PMID: 30118588; PMCID: PMC6343479. 3. Mdachi RE, Thuita JK, Kagira JM, Ngotho JM, Murilla GA, Ndung'u JM, Tidwell RR, Hall JE, Brun R. Efficacy of the novel diamidine compound 2,5-Bis(4-amidinophenyl)- furan-bis-O-Methlylamidoxime (Pafuramidine, DB289) against Trypanosoma brucei rhodesiense infection in vervet monkeys after oral administration. Antimicrob Agents Chemother. 2009 Mar;53(3):953-7. doi: 10.1128/AAC.00831-08. Epub 2008 Dec 8. PMID: 19064893; PMCID: PMC2650535. 4. Thuita JK, Karanja SM, Wenzler T, Mdachi RE, Ngotho JM, Kagira JM, Tidwell R, Brun R. Efficacy of the diamidine DB75 and its prodrug DB289, against murine models of human African trypanosomiasis. Acta Trop. 2008 Oct;108(1):6-10. doi: 10.1016/j.actatropica.2008.07.006. Epub 2008 Aug 5. PMID: 18722336.
In vitro protocol:	1. An X, Lee J, Kim GH, Kim HJ, Pyo HJ, Kwon I, Cho H. Modulation of IKs channel-PIP2 interaction by PRMT1 plays a critical role in the control of cardiac repolarization. J Cell Physiol. 2022 Jul;237(7):3069-3079. doi: 10.1002/jcp.30775. Epub 2022 May 17. PMID: 35580065; PMCID: PMC9543859. 2. Jenquin JR, Coonrod LA, Silverglate QA, Pellitier NA, Hale MA, Xia G, Nakamori M, Berglund JA. Furamidine Rescues Myotonic Dystrophy Type I Associated Mis-Splicing through Multiple Mechanisms. ACS Chem Biol. 2018 Sep 21;13(9):2708-2718. doi: 10.1021/acschembio.8b00646. Epub 2018 Aug 27. PMID: 30118588; PMCID: PMC6343479.
In vivo protocol:	1. Mdachi RE, Thuita JK, Kagira JM, Ngotho JM, Murilla GA, Ndung'u JM, Tidwell RR, Hall JE, Brun R. Efficacy of the novel diamidine compound 2,5-Bis(4-amidinophenyl)- furan-bis-O-Methlylamidoxime (Pafuramidine, DB289) against Trypanosoma brucei rhodesiense infection in vervet monkeys after oral administration. Antimicrob Agents Chemother. 2009 Mar;53(3):953-7. doi: 10.1128/AAC.00831-08. Epub 2008 Dec 8. PMID: 19064893; PMCID: PMC2650535. 2. Thuita JK, Karanja SM, Wenzler T, Mdachi RE, Ngotho JM, Kagira JM, Tidwell R, Brun R. Efficacy of the diamidine DB75 and its prodrug DB289, against murine models of human African trypanosomiasis. Acta Trop. 2008 Oct;108(1):6-10. doi: 10.1016/j.actatropica.2008.07.006. Epub 2008 Aug 5. PMID: 18722336.

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21: Ismail MA, Arafa RK, Brun R, Wenzler T, Miao Y, Wilson WD, Generaux C, Bridges A, Hall JE, Boykin DW. Synthesis, DNA affinity, and antiprotozoal activity of linear dications: Terphenyl diamidines and analogues. J Med Chem. 2006 Aug 24;49(17):5324-32. PubMed PMID: 16913722.

22: Werbovetz K. Diamidines as antitrypanosomal, antileishmanial and antimalarial agents. Curr Opin Investig Drugs. 2006 Feb;7(2):147-57. Review. PubMed PMID: 16499285.

23: Saulter JY, Kurian JR, Trepanier LA, Tidwell RR, Bridges AS, Boykin DW, Stephens CE, Anbazhagan M, Hall JE. Unusual dehydroxylation of antimicrobial amidoxime prodrugs by cytochrome b5 and NADH cytochrome b5 reductase. Drug Metab Dispos. 2005 Dec;33(12):1886-93. Epub 2005 Aug 30. PubMed PMID: 16131524.

24: Yeramian P, Meshnick SR, Krudsood S, Chalermrut K, Silachamroon U, Tangpukdee N, Allen J, Brun R, Kwiek JJ, Tidwell R, Looareesuwan S. Efficacy of DB289 in Thai patients with Plasmodium vivax or acute, uncomplicated Plasmodium falciparum infections. J Infect Dis. 2005 Jul 15;192(2):319-22. Epub 2005 Jun 7. PubMed PMID: 15962227.

25: Jannin J, Cattand P. Treatment and control of human African trypanosomiasis. Curr Opin Infect Dis. 2004 Dec;17(6):565-71. Review. PubMed PMID: 15640711.

26: Sturk LM, Brock JL, Bagnell CR, Hall JE, Tidwell RR. Distribution and quantitation of the anti-trypanosomal diamidine 2,5-bis(4-amidinophenyl)furan (DB75) and its N-methoxy prodrug DB289 in murine brain tissue. Acta Trop. 2004 Jul;91(2):131-43. PubMed PMID: 15234662.

27: Zhou L, Thakker DR, Voyksner RD, Anbazhagan M, Boykin DW, Hall JE, Tidwell RR. Metabolites of an orally active antimicrobial prodrug, 2,5-bis(4-amidinophenyl)furan-bis-O-methylamidoxime, identified by liquid chromatography/tandem mass spectrometry. J Mass Spectrom. 2004 Apr;39(4):351-60. PubMed PMID: 15103648.

28: New oral drug for PCP. AIDS Patient Care STDS. 2003 Nov;17(11):609-10. PubMed PMID: 14748360.

29: Yeates C. DB-289 Immtech International. IDrugs. 2003 Nov;6(11):1086-93. Review. PubMed PMID: 14600842.

30: Givens MD, Dykstra CC, Brock KV, Stringfellow DA, Kumar A, Stephens CE, Goker H, Boykin DW. Detection of inhibition of bovine viral diarrhea virus by aromatic cationic molecules. Antimicrob Agents Chemother. 2003 Jul;47(7):2223-30. PubMed PMID: 12821472; PubMed Central PMCID: PMC161853.

31: Zhou L, Lee K, Thakker DR, Boykin DW, Tidwell RR, Hall JE. Enhanced permeability of the antimicrobial agent 2,5-bis(4-amidinophenyl)furan across Caco-2 cell monolayers via its methylamidoidme prodrug. Pharm Res. 2002 Nov;19(11):1689-95. PubMed PMID: 12458675.

32: Legros D, Ollivier G, Gastellu-Etchegorry M, Paquet C, Burri C, Jannin J, Büscher P. Treatment of human African trypanosomiasis--present situation and needs for research and development. Lancet Infect Dis. 2002 Jul;2(7):437-40. Review. PubMed PMID: 12127356.

33: Zhou L, Voyksner RD, Thakker DR, Stephens CE, Anbazhagan M, Boykin DW, Hall JE, Tidwell RR. Characterizing the fragmentation of 2,5-bis (4-amidinophenyl)furan-bis-O-methylamidoxime and selected metabolites using ion trap mass spectrometry. Rapid Commun Mass Spectrom. 2002;16(11):1078-85. PubMed PMID: 11992511.

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