Eniluracil | GW776 | GW776C85 | CAS#59989-18-3

MedKoo Cat#: 201250 | Name: Eniluracil

Featured

Description:

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

Eniluracil, also known as GW776 and GW776C85, is an orally active and irreversible inhibitor of dihydropyrimidine dehydrogenase. Eniluracil inhibits dihydropyrimidine dehydrogenase, the rate-limiting enzyme that catabolizes and inactivates 5-fluorouracil (5-FU) in the liver. Co-administration of ethynyluracil permits the oral administration of 5-FU. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Chemical Structure

Eniluracil

CAS#59989-18-3

Theoretical Analysis

MedKoo Cat#: 201250

Name: Eniluracil

CAS#: 59989-18-3

Chemical Formula: C6H4N2O2

Exact Mass: 136.0273

Molecular Weight: 136.11

Elemental Analysis: C, 52.95; H, 2.96; N, 20.58; O, 23.51

Price and Availability

Size	Price	Availability
50mg	USD 250.00	2 Weeks
100mg	USD 450.00	2 Weeks
250mg	USD 900.00	2 Weeks

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

No Data

Synonym

776C85; GW776; GW-776; GW 776; GW-776C85; GW 776C85; GW776C85; NSC 687296; NSC687296; NSC-687296; 5-Ethynyluracil; Eniluracilo;

IUPAC/Chemical Name

5-ethynylpyrimidine-2,4(1H,3H)-dione.

InChi Key

JOZGNYDSEBIJDH-UHFFFAOYSA-N

InChi Code

InChI=1S/C6H4N2O2/c1-2-4-3-7-6(10)8-5(4)9/h1,3H,(H2,7,8,9,10)

SMILES Code

O=C1NC(C(C#C)=CN1)=O

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

More Info

Eniluracil plus 5‑FU was previously being developed by GlaxoSmithKline (GSK). Although the therapy was successful in Phase I and Phase II clinical trials, it tended to produce less antitumor activity than the control therapy in two Phase III trials. Development was subsequently stopped. Since then, Adherex has learned that with the dose and schedule used in the previous GSK Phase III trials may not have been optimal. Preclinical studies have shown that when eniluracil is present in high ratios to 5‑FU, it decreases the antitumor activity. In the Phase III trials, the eniluracil:5‑FU ratio was 10:1. see: http://adherex.com/product-candidate/eniluracil-clinical-development/ Eniluracil is a potent inactivator of dihydropyrimidine dehydrogenase (uracil reductase), the enzyme that rapidly catabolizes 5-fluorouracil (5-FU). Although eniluracil in combination with 5-FU was promising in phase I and II studies, in 2 multicenter phase III colorectal cancer studies, eniluracil dosed in a 10-to-1 ratio to 5-FU produced less antitumor benefit than the std. regimen of 5-FU/leucovorin without eniluracil. Clinical Colorectal Cancer (2010), 9(1), 52-54.

Instruction

View handling instruction

Preparing Stock Solutions

The following data is based on the product molecular weight 136.11 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

1: Schilsky RL, Kindler HL. Eniluracil: an irreversible inhibitor of dihydropyrimidine dehydrogenase. Expert Opin Investig Drugs. 2000 Jul;9(7):1635-49. doi: 10.1517/13543784.9.7.1635. PMID: 11060767. 2: Hohneker JA. Clinical development of eniluracil: current status. Oncology (Williston Park). 1998 Oct;12(10 Suppl 7):52-6. PMID: 9830627. 3: Levin J, Hohneker J. Clinical development of eniluracil/fluorouracil: an oral treatment for patients with solid tumors. Invest New Drugs. 2000 Nov;18(4):383-90. doi: 10.1023/a:1006457617467. PMID: 11081574. 4: Baker SD. Pharmacology of fluorinated pyrimidines: eniluracil. Invest New Drugs. 2000 Nov;18(4):373-81. doi: 10.1023/a:1006453500629. PMID: 11081573. 5: Rivera E, Chang JC, Semiglazov V, Burdaeva O, Kirby MG, Spector T. Eniluracil plus 5-fluorouracil and leucovorin: treatment for metastatic breast cancer patients in whom capecitabine treatment rapidly failed. Clin Breast Cancer. 2014 Feb;14(1):26-30. doi: 10.1016/j.clbc.2013.08.018. Epub 2013 Nov 1. PMID: 24183612. 6: Benson AB 3rd. Oral eniluracil/5-FU for advanced colon and breast carcinomas. Oncology (Williston Park). 2001 Jan;15(1 Suppl 2):57-63; discussion 64. PMID: 11219979. 7: Bading JR, Alauddin MM, Fissekis JD, Shahinian AH, Joung J, Spector T, Conti PS. Blocking catabolism with eniluracil enhances PET studies of 5-[18F]fluorouracil pharmacokinetics. J Nucl Med. 2000 Oct;41(10):1714-24. PMID: 11038003. 8: Ahmed FY, Johnston SJ, Cassidy J, O'Kelly T, Binnie N, Murray GI, van Gennip AH, Abeling NG, Knight S, McLeod HL. Eniluracil treatment completely inactivates dihydropyrimidine dehydrogenase in colorectal tumors. J Clin Oncol. 1999 Aug;17(8):2439-45. doi: 10.1200/JCO.1999.17.8.2439. PMID: 10561307. 9: Spector T, Cao S. A possible cause and remedy for the clinical failure of 5-fluorouracil plus eniluracil. Clin Colorectal Cancer. 2010 Jan;9(1):52-4. doi: 10.3816/CCC.2010.n.007. PMID: 20100689. 10: Paff MT, Baccanari DP, Davis ST, Cao S, Tansik RL, Rustum YM, Spector T. Preclinical development of eniluracil: enhancing the therapeutic index and dosing convenience of 5-fluorouracil. Invest New Drugs. 2000 Nov;18(4):365-71. doi: 10.1023/a:1006401432488. PMID: 11081572. 11: Saleem A, Yap J, Osman S, Brady F, Suttle B, Lucas SV, Jones T, Price PM, Aboagye EO. Modulation of fluorouracil tissue pharmacokinetics by eniluracil: in-vivo imaging of drug action. Lancet. 2000 Jun 17;355(9221):2125-31. doi: 10.1016/s0140-6736(00)02380-1. PMID: 10902627. 12: Benson AB 3rd, Mitchell E, Abramson N, Klencke B, Ritch P, Burnhan JP, McGuirt C, Bonny T, Levin J, Hohneker J. Oral eniluracil/5-fluorouracil in patients with inoperable hepatocellular carcinoma. Ann Oncol. 2002 Apr;13(4):576-81. doi: 10.1093/annonc/mdf079. PMID: 12056708. 13: Heslin MJ, Yan J, Weiss H, Shao L, Owens J, Lucas VS, Diasio RB. Dihydropyrimidine dehydrogenase (DPD) rapidly regenerates after inactivation by eniluracil (GW776C85) in primary and metastatic colorectal cancer. Cancer Chemother Pharmacol. 2003 Nov;52(5):399-404. doi: 10.1007/s00280-003-0681-1. Epub 2003 Aug 7. PMID: 12904894. 14: Shepard DR, Mani S, Kastrissios H, Learned-Coughlin S, Smith D, Ertel P, Magnum S, Janisch L, Fleming GF, Schilsky RL, Ratain MJ. Estimation of the effect of food on the disposition of oral 5-fluorouracil in combination with eniluracil. Cancer Chemother Pharmacol. 2002 May;49(5):398-402. doi: 10.1007/s00280-002-0431-9. Epub 2002 Feb 23. PMID: 11976834. 15: Czito BG, Hong TJ, Cohen DP, Petros WP, Tyler DS, Pappas TN, Yu D, Lee CG, Lockhart AC, Morse MA, Fernando N, Hurwitz HI. A phase I study of eniluracil/5-FU in combination with radiation therapy for potentially resectable and/or unresectable cancer of the pancreas and distal biliary tract. Cancer Invest. 2006 Feb;24(1):9-17. doi: 10.1080/07357900500449454. PMID: 16466986. 16: Sacchetti M, Varlashkin PG, Long ST, Lancaster RW. Crystal structure prediction for eniluracil. J Pharm Sci. 2001 Aug;90(8):1049-55. doi: 10.1002/jps.1058. PMID: 11536209. 17: Czito BG, Hong TJ, Cohen DP, Tyler DS, Lee CG, Anscher MS, Ludwig KA, Seigler HF, Mantyh C, Morse MA, Lockhart AC, Petros WP, Honeycutt W, Spector NL, Ertel PJ, Mangum SG, Hurwitz HI. A Phase I trial of preoperative eniluracil plus 5-fluorouracil and radiation for locally advanced or unresectable adenocarcinoma of the rectum and colon. Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):779-85. doi: 10.1016/S0360-3016(03)01567-0. PMID: 14967434. 18: Morgan-Meadows S, Thomas JP, Mulkerin D, Berlin JD, Bailey H, Binger K, Volkman J, Alberti D, Feierabend C, Marrocha R, Arzoomanian RZ, Wilding G. Phase I study of eniluracil, oral 5-fluororacil and gemcitabine in patients with advanced malignancy. Invest New Drugs. 2002 Nov;20(4):377-82. doi: 10.1023/a:1020673928704. PMID: 12448654. 19: Baker SD, Diasio RB, O'Reilly S, Lucas VS, Khor SP, Sartorius SE, Donehower RC, Grochow LB, Spector T, Hohneker JA, Rowinsky EK. Phase I and pharmacologic study of oral fluorouracil on a chronic daily schedule in combination with the dihydropyrimidine dehydrogenase inactivator eniluracil. J Clin Oncol. 2000 Feb;18(4):915-26. doi: 10.1200/JCO.2000.18.4.915. PMID: 10673535. 20: Ochoa L, Hurwitz HI, Wilding G, Cohen D, Thomas JP, Schwartz G, Monroe P, Petros WP, Ertel VP, Hsieh A, Hoffman C, Drengler R, Magnum S, Rowinsky EK. Pharmacokinetics and bioequivalence of a combined oral formulation of eniluracil, an inactivator of dihydropyrimidine dehydrogenase, and 5-fluorouracil in patients with advanced solid malignancies. Ann Oncol. 2000 Oct;11(10):1313-22. doi: 10.1023/a:1008379802642. PMID: 11106122.