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MedKoo Cat#: 524216 | Name: AMG-517
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Description:

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

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

AMG-517
AMG-517
CAS#659730-32-2

Theoretical Analysis

MedKoo Cat#: 524216

Name: AMG-517

CAS#: 659730-32-2

Chemical Formula: C20H13F3N4O2S

Exact Mass: 430.0711

Molecular Weight: 430.40

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
50mg USD 450.00 2 Weeks
100mg USD 750.00 2 Weeks
200mg USD 1,250.00 2 Weeks
500mg USD 2,650.00 2 Weeks
1g USD 3,750.00 2 Weeks
2g USD 6,250.00 2 Weeks
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Related CAS #
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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
More Info
Product Data
Product Data
Instruction
View handling instruction
Biological target:
AMG 517 is a potent and selective vanilloid receptor-1 (TRPV1) antagonist with an IC50 of 0.5 nM.
In vitro activity:
AMG 517 inhibited capsaicin, pH 5, and heat-induced 45Ca2+ uptake into cells expressing TRPV1 with IC50 values of 1 to 2 nM (Table 1, Fig. 1A). AMG 517 blocked capsaicin-, proton-, and heat-induced inward currents in TRPV1-expressing cells similarly (data not shown). In addition, AMG 517 acted as a potent antagonist of all of the endogenous ligands tested (Table 1). AMG 517 inhibited native TRPV1 activation by capsaicin in rat dorsal root ganglion neurons with an IC50 value of 0.68 ± 0.2 nM. AMG 517 is a competitive antagonist of both rat and human TRPV1 with dissociation constant (Kb) values of 4.2 and 6.2 nM, respectively (Fig. 1, B–E). AMG 517 did not activate TRPV1 at concentrations up to 40 μM, as measured by 45Ca2+ uptake into TRPV1-expressing cells, indicating that it was not a partial agonist. Pharmacology of another TRPV1 antagonist, AMG8163 (a “tert-butyloxycarbonyl” analog of AMG 517), used in this study was reported recently. Reference: J Pharmacol Exp Ther. 2007 Oct;323(1):128-37. https://pubmed.ncbi.nlm.nih.gov/17652633/
In vivo activity:
There was no obvious difference in the number of axons in the one-week injury-only rat group compared with the group treated with AMG-517. However, two weeks of AMG-517 treatment induced strong regeneration of axons in the proximal stump compared with the untreated control group (Figure 3, p < 0.001). Moreover, the sciatic nerve axons with two weeks of AMG-517 treatment were well organized and included both myelinated and nonmyelinated regenerating axons (Figure 3(a)). Reference: Mol Pain. 2018; 14: 1744806918777614. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6009083/
Solvent mg/mL mM comments
Solubility
DMSO 46.3 107.46
DMF 112.5 261.38
Ethanol 3.3 7.67
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 430.40 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
Formulation protocol:
1. Gavva NR, Bannon AW, Hovland DN Jr, Lehto SG, Klionsky L, Surapaneni S, Immke DC, Henley C, Arik L, Bak A, Davis J, Ernst N, Hever G, Kuang R, Shi L, Tamir R, Wang J, Wang W, Zajic G, Zhu D, Norman MH, Louis JC, Magal E, Treanor JJ. Repeated administration of vanilloid receptor TRPV1 antagonists attenuates hyperthermia elicited by TRPV1 blockade. J Pharmacol Exp Ther. 2007 Oct;323(1):128-37. doi: 10.1124/jpet.107.125674. Epub 2007 Jul 25. PMID: 17652633. 2. Hai J, Kawabata F, Uchida K, Nishimura S, Tabata S. Intragastric administration of AMG517, a TRPV1 antagonist, enhanced activity-dependent energy metabolism via capsaicin-sensitive sensory nerves in mice. Biosci Biotechnol Biochem. 2020 Oct;84(10):2121-2127. doi: 10.1080/09168451.2020.1789836. Epub 2020 Jul 7. PMID: 32633621. 3. Bai J, Liu F, Wu LF, Wang YF, Li XQ. Attenuation of TRPV1 by AMG-517 after nerve injury promotes peripheral axonal regeneration in rats. Mol Pain. 2018 Jan-Dec;14:1744806918777614. doi: 10.1177/1744806918777614. Epub 2018 May 17. PMID: 29768956; PMCID: PMC6009083.
In vitro protocol:
1. Gavva NR, Bannon AW, Hovland DN Jr, Lehto SG, Klionsky L, Surapaneni S, Immke DC, Henley C, Arik L, Bak A, Davis J, Ernst N, Hever G, Kuang R, Shi L, Tamir R, Wang J, Wang W, Zajic G, Zhu D, Norman MH, Louis JC, Magal E, Treanor JJ. Repeated administration of vanilloid receptor TRPV1 antagonists attenuates hyperthermia elicited by TRPV1 blockade. J Pharmacol Exp Ther. 2007 Oct;323(1):128-37. doi: 10.1124/jpet.107.125674. Epub 2007 Jul 25. PMID: 17652633.
In vivo protocol:
1. Hai J, Kawabata F, Uchida K, Nishimura S, Tabata S. Intragastric administration of AMG517, a TRPV1 antagonist, enhanced activity-dependent energy metabolism via capsaicin-sensitive sensory nerves in mice. Biosci Biotechnol Biochem. 2020 Oct;84(10):2121-2127. doi: 10.1080/09168451.2020.1789836. Epub 2020 Jul 7. PMID: 32633621. 2. Bai J, Liu F, Wu LF, Wang YF, Li XQ. Attenuation of TRPV1 by AMG-517 after nerve injury promotes peripheral axonal regeneration in rats. Mol Pain. 2018 Jan-Dec;14:1744806918777614. doi: 10.1177/1744806918777614. Epub 2018 May 17. PMID: 29768956; PMCID: PMC6009083.
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.