AMG-517
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    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 524216

CAS#: 659730-32-2

Description: AMG 517 is a potent and selective TRPV1 antagonist, and antagonizes capsaicin, proton, and heat activation of TRPV1. The transient receptor potential vanilloid-1 (TRPV1) channel plays a suppressive role in the systemic inflammatory response syndrome (SIRS) by inhibiting production of tumor necrosis factor (TNF)α and possibly by other mechanisms. TRPV1 antagonists, widely viewed as new-generation painkillers, may decrease the resistance of older patients to infection and sepsis.


Chemical Structure

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AMG-517
CAS# 659730-32-2

Theoretical Analysis

MedKoo Cat#: 524216
Name: AMG-517
CAS#: 659730-32-2
Chemical Formula: C20H13F3N4O2S
Exact Mass: 430.07113
Molecular Weight: 430.4
Elemental Analysis: C, 55.81; H, 3.04; F, 13.24; N, 13.02; O, 7.43; S, 7.45

Price and Availability

Size Price Availability Quantity
100.0mg USD 650.0 2 Weeks
200.0mg USD 1050.0 2 Weeks
500.0mg USD 1950.0 2 Weeks
1.0g USD 2950.0 2 Weeks
2.0g USD 3950.0 2 Weeks
5.0g USD 5850.0 2 Weeks
Bulk inquiry

Synonym: AMG-517; AMG 517; AMG517; BD-0082;

IUPAC/Chemical Name: Acetamide, N-(4-((6-(4-(trifluoromethyl)phenyl)-4-pyrimidinyl)oxy)-2-benzothiazolyl)-

InChi Key: YUTIXVXZQIQWGY-UHFFFAOYSA-N

InChi Code: InChI=1S/C20H13F3N4O2S/c1-11(28)26-19-27-18-15(3-2-4-16(18)30-19)29-17-9-14(24-10-25-17)12-5-7-13(8-6-12)20(21,22)23/h2-10H,1H3,(H,26,27,28)

SMILES Code: CC(NC1=NC2=C(OC3=NC=NC(C4=CC=C(C(F)(F)F)C=C4)=C3)C=CC=C2S1)=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

Preparing Stock Solutions

The following data is based on the product molecular weight 430.4 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.

Recalculate based on batch purity %
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

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1: Green D, Ruparel S, Gao X, Ruparel N, Patil M, Akopian A, Hargreaves K. Central activation of TRPV1 and TRPA1 by novel endogenous agonists contributes to mechanical allodynia and thermal hyperalgesia after burn injury. Mol Pain. 2016 Jul 12;12. pii: 1744806916661725. doi: 10.1177/1744806916661725. PubMed PMID: 27411353; PubMed Central PMCID: PMC4955965.

2: Calahan JL, Azali SC, Munson EJ, Nagapudi K. Investigation of Phase Mixing in Amorphous Solid Dispersions of AMG 517 in HPMC-AS Using DSC, Solid-State NMR, and Solution Calorimetry. Mol Pharm. 2015 Nov 2;12(11):4115-23. doi: 10.1021/acs.molpharmaceut.5b00556. PubMed PMID: 26457879.

3: Daurio D, Nagapudi K, Li L, Quan P, Nunez FA. Application of twin screw extrusion to the manufacture of cocrystals: scale-up of AMG 517-sorbic acid cocrystal production. Faraday Discuss. 2014;170:235-49. doi: 10.1039/c3fd00153a. PubMed PMID: 25406487.

4: Soto M, Pham R, Almon V, Wagner M, Primack R, Ponce M, Meyer J, James CA, Salyers KL, Retter MW. Evaluation of matrix microsampling methods for therapeutic drug candidate quantification in discovery-stage rodent pharmacokinetic studies. Bioanalysis. 2014 Aug;6(16):2135-46. doi: 10.4155/bio.14.184. PubMed PMID: 25331858.

5: Green DP, Ruparel S, Roman L, Henry MA, Hargreaves KM. Role of endogenous TRPV1 agonists in a postburn pain model of partial-thickness injury. Pain. 2013 Nov;154(11):2512-20. doi: 10.1016/j.pain.2013.07.040. PubMed PMID: 23891895; PubMed Central PMCID: PMC3821162.

6: Calahan JL, Zanon RL, Alvarez-Nunez F, Munson EJ. Isothermal microcalorimetry to investigate the phase separation for amorphous solid dispersions of AMG 517 with HPMC-AS. Mol Pharm. 2013 May 6;10(5):1949-57. doi: 10.1021/mp300714g. PubMed PMID: 23574401.

7: Luu V, Jona J, Stanton MK, Peterson ML, Morrison HG, Nagapudi K, Tan H. High-throughput 96-well solvent mediated sonic blending synthesis and on-plate solid/solution stability characterization of pharmaceutical cocrystals. Int J Pharm. 2013 Jan 30;441(1-2):356-64. doi: 10.1016/j.ijpharm.2012.11.020. PubMed PMID: 23178596.

8: Nash MS, McIntyre P, Groarke A, Lilley E, Culshaw A, Hallett A, Panesar M, Fox A, Bevan S. 7-tert-Butyl-6-(4-chloro-phenyl)-2-thioxo-2,3-dihydro-1H-pyrido[2,3-d]pyrimidin-4 -one, a classic polymodal inhibitor of transient receptor potential vanilloid type 1 with a reduced liability for hyperthermia, is analgesic and ameliorates visceral hypersensitivity. J Pharmacol Exp Ther. 2012 Aug;342(2):389-98. doi: 10.1124/jpet.112.191932. PubMed PMID: 22566669.

9: Kort ME, Kym PR. TRPV1 antagonists: clinical setbacks and prospects for future development. Prog Med Chem. 2012;51:57-70. doi: 10.1016/B978-0-12-396493-9.00002-9. Review. PubMed PMID: 22520471.

10: Wanner SP, Garami A, Pakai E, Oliveira DL, Gavva NR, Coimbra CC, Romanovsky AA. Aging reverses the role of the transient receptor potential vanilloid-1 channel in systemic inflammation from anti-inflammatory to proinflammatory. Cell Cycle. 2012 Jan 15;11(2):343-9. doi: 10.4161/cc.11.2.18772. PubMed PMID: 22214765; PubMed Central PMCID: PMC3293383.

11: Uyeda C, Pham R, Fide S, Henne K, Xu G, Soto M, James C, Wong P. Application of automated dried blood spot sampling and LC-MS/MS for pharmacokinetic studies of AMG 517 in rats. Bioanalysis. 2011 Oct;3(20):2349-56. doi: 10.4155/bio.11.227. PubMed PMID: 22011182.

12: Wong P, Pham R, Whitely C, Soto M, Salyers K, James C, Bruenner BA. Application of automated serial blood sampling and dried blood spot technique with liquid chromatography-tandem mass spectrometry for pharmacokinetic studies in mice. J Pharm Biomed Anal. 2011 Nov 1;56(3):604-8. doi: 10.1016/j.jpba.2011.06.022. PubMed PMID: 21784595.

13: Stanton MK, Kelly RC, Colletti A, Langley M, Munson EJ, Peterson ML, Roberts J, Wells M. Improved pharmacokinetics of AMG 517 through co-crystallization part 2: analysis of 12 carboxylic acid co-crystals. J Pharm Sci. 2011 Jul;100(7):2734-43. doi: 10.1002/jps.22502. PubMed PMID: 21287556.

14: Stanton MK, Kelly RC, Colletti A, Kiang YH, Langley M, Munson EJ, Peterson ML, Roberts J, Wells M. Improved pharmacokinetics of AMG 517 through co-crystallization. Part 1: comparison of two acids with corresponding amide co-crystals. J Pharm Sci. 2010 Sep;99(9):3769-78. doi: 10.1002/jps.22181. PubMed PMID: 20665842.

15: Silva Elipe MV, Tan ZJ, Ronk M, Bostick T. A Multidisciplinary Investigation to Determine the Structure and Source of Dimeric Impurities in AMG 517 Drug Substance. Int J Anal Chem. 2009;2009:768743. doi: 10.1155/2009/768743. PubMed PMID: 20140079; PubMed Central PMCID: PMC2814138.

16: Medina C, Daurio D, Nagapudi K, Alvarez-Nunez F. Manufacture of pharmaceutical co-crystals using twin screw extrusion: a solvent-less and scalable process. J Pharm Sci. 2010 Apr;99(4):1693-6. doi: 10.1002/jps.21942. PubMed PMID: 19774652.

17: Kym PR, Kort ME, Hutchins CW. Analgesic potential of TRPV1 antagonists. Biochem Pharmacol. 2009 Aug 1;78(3):211-6. doi: 10.1016/j.bcp.2009.02.014. PubMed PMID: 19481638.

18: Kennedy M, Hu J, Gao P, Li L, Ali-Reynolds A, Chal B, Gupta V, Ma C, Mahajan N, Akrami A, Surapaneni S. Enhanced bioavailability of a poorly soluble VR1 antagonist using an amorphous solid dispersion approach: a case study. Mol Pharm. 2008 Nov-Dec;5(6):981-93. doi: 10.1021/mp800061r. PubMed PMID: 19434920.

19: Wong GY, Gavva NR. Therapeutic potential of vanilloid receptor TRPV1 agonists and antagonists as analgesics: Recent advances and setbacks. Brain Res Rev. 2009 Apr;60(1):267-77. doi: 10.1016/j.brainresrev.2008.12.006. Review. PubMed PMID: 19150372.

20: Gavva NR. Body-temperature maintenance as the predominant function of the vanilloid receptor TRPV1. Trends Pharmacol Sci. 2008 Nov;29(11):550-7. doi: 10.1016/j.tips.2008.08.003. Review. PubMed PMID: 18805596.

AMG-517

100.0mg / USD 650.0