Avoralstat | BCX-4161 | CAS#918407-35-9 | Kallikrein inhibitor |MedKoo

MedKoo Cat#: 319539 | Name: Avoralstat

Description:

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

Avoralstat, also known as BCX-4161, is a potent and orally active Kallikrein inhibitor and Bradykinin inhibitor. Avoralstat may be potentially useful for treatment for Hereditary angioedema. Avoralstat inhibits plasma kallikrein and suppresses bradykinin production. Bradykinin is the mediator of acute swelling attacks in HAE patients.

Chemical Structure

Avoralstat

CAS#918407-35-9

Theoretical Analysis

MedKoo Cat#: 319539

Name: Avoralstat

CAS#: 918407-35-9

Chemical Formula: C28H27N5O5

Exact Mass: 513.2012

Molecular Weight: 513.55

Elemental Analysis: C, 65.49; H, 5.30; N, 13.64; O, 15.58

Price and Availability

Size	Price	Availability
5mg	USD 110.00	Ready to ship
10mg	USD 185.00	Ready to ship
25mg	USD 385.00	Ready to ship
50mg	USD 650.00	Ready to ship
100mg	USD 1,100.00	Ready to ship
200mg	USD 1,870.00	Ready to ship

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Related CAS #

No Data

Synonym

BCX-4161; BCX 4161; BCX4161; Avoralstat;

IUPAC/Chemical Name

3-{2-[(4-carbamimidoylphenyl)carbamoyl]-4-ethenyl-5-methoxyphenyl}-6-[(cyclopropylmethyl)carbamoyl]pyridine-2-carboxylic acid

InChi Key

TUWMKPVJGGWGNL-UHFFFAOYSA-N

InChi Code

InChI=1S/C28H27N5O5/c1-3-16-12-21(26(34)32-18-8-6-17(7-9-18)25(29)30)20(13-23(16)38-2)19-10-11-22(33-24(19)28(36)37)27(35)31-14-15-4-5-15/h3,6-13,15H,1,4-5,14H2,2H3,(H3,29,30)(H,31,35)(H,32,34)(H,36,37)

SMILES Code

O=C(C1=NC(C(NCC2CC2)=O)=CC=C1C3=CC(OC)=C(C=C)C=C3C(NC4=CC=C(C(N)=N)C=C4)=O)O

Appearance

Solid powder

Purity

>95% (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

Certificate of Analysis

View CoA: current batch, Lot#S21S10C09

QC Data

View QC data: current batch, Lot#S21S10C09

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Avoralstat (BCX4161), a potent and orally active plasma kallikrein (PKK) inhibitor, is used for hereditary angioedema research.

In vitro activity:

The inhibitory potential of human drugs available for repositioning, including avoralstat, PCI-27483, and antipain, along with SBTI was focused on. A biochemical inhibition assay using the extracellular region of purified recombinant TMPRSS2 (residues 106–492) was utilized to test inhibition by these compounds. Strikingly, avoralstat was more than 18-fold more selective toward TMPRSS2 than other S1 proteases. Avoralstat displayed potent inhibition of other S1 proteases, consistent with their proximity to TMPRSS2 in the 3DPhyloFold tree, while displaying no inhibition of non–S1 proteases. Notably, avoralstat inhibited several proteins that were structurally similar to TMPRSS2, including factor VIIa and tryptase b2, despite being distant in primary sequence. Taken together, these results suggested avoralstat was highly selective for TMPRSS2. Reference: J Clin Invest. 2021 May 17; 131(10): e147973. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121520/

In vivo activity:

Using a mouse model of SARS-CoV-2 lung infection (Ad5-hACE2 transduced WT BALB/c mice) (17), the efficacy of avoralstat and camostat in modifying SARS-CoV-2 infection was compared. Cohorts of mice were infected (i.n.) with either 3 × 103 or 1 × 105 PFU of SARS-CoV-2. Mice were treated with avoralstat, camostat (30 mg/kg i.p. injection), or vehicle (DMSO). Avoralstat significantly reduced the lung tissue titers in both cohorts. Strikingly, the lung tissue virus titers were below the limit of detection in 3 of 4 avoralstat-treated mice. Moreover, avoralstat still showed a significant weight rescue effect beginning from 7 days after infection. Thus, the inhibitory effect of avoralstat observed in biochemical and cell assays extended to prophylactic treatment of mice infected with escalating doses of SARS-CoV-2. Reference: J Clin Invest. 2021 May 17; 131(10): e147973. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121520/

	Solvent	mg/mL	mM
Solubility
	DMSO	50.0	97.36

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 513.55 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: Beard N, Frese M, Smertina E, Mere P, Katelaris C, Mills K. Interventions for the long-term prevention of hereditary angioedema attacks. Cochrane Database Syst Rev. 2022 Nov 3;11(11):CD013403. doi: 10.1002/14651858.CD013403.pub2. PMID: 36326435; PMCID: PMC9632406. 2: Wagoner J, Herring S, Hsiang TY, Ianevski A, Biering SB, Xu S, Hoffmann M, Pöhlmann S, Gale M Jr, Aittokallio T, Schiffer JT, White JM, Polyak SJ. Combinations of Host- and Virus-Targeting Antiviral Drugs Confer Synergistic Suppression of SARS-CoV-2. Microbiol Spectr. 2022 Oct 26;10(5):e0333122. doi: 10.1128/spectrum.03331-22. Epub 2022 Oct 3. PMID: 36190406; PMCID: PMC9718484. 3: Iype E, Pillai U J, Kumar I, Gaastra-Nedea SV, Subramanian R, Saha RN, Dutta M. In silico and in vitro assays reveal potential inhibitors against 3CLpro main protease of SARS-CoV-2. J Biomol Struct Dyn. 2022;40(23):12800-12811. doi: 10.1080/07391102.2021.1977181. Epub 2021 Sep 22. PMID: 34550861. 4: Sun YJ, Velez G, Parsons DE, Li K, Ortiz ME, Sharma S, McCray PB Jr, Bassuk AG, Mahajan VB. Structure-based phylogeny identifies avoralstat as a TMPRSS2 inhibitor that prevents SARS-CoV-2 infection in mice. J Clin Invest. 2021 May 17;131(10):e147973. doi: 10.1172/JCI147973. PMID: 33844653; PMCID: PMC8121520. 5: Aygören-Pürsün E, Magerl M, Graff J, Martinez-Saguer I, Kreuz W, Longhurst H, Nasr I, Bas M, Straßen U, Fang L, Cornpropst M, Dobo S, Collis P, Sheridan WP, Maurer M. Prophylaxis of hereditary angioedema attacks: A randomized trial of oral plasma kallikrein inhibition with avoralstat. J Allergy Clin Immunol. 2016 Sep;138(3):934-936.e5. doi: 10.1016/j.jaci.2016.03.043. Epub 2016 May 11. PMID: 27302552. 6: Cornpropst M, Collis P, Collier J, Babu YS, Wilson R, Zhang J, Fang L, Zong J, Sheridan WP. Safety, pharmacokinetics, and pharmacodynamics of avoralstat, an oral plasma kallikrein inhibitor: phase 1 study. Allergy. 2016 Dec;71(12):1676-1683. doi: 10.1111/all.12930. Epub 2016 Jul 20. PMID: 27154593. 7: Riedl MA, Aygören-Pürsün E, Baker J, Farkas H, Anderson J, Bernstein JA, Bouillet L, Busse P, Manning M, Magerl M, Gompels M, Huissoon AP, Longhurst H, Lumry W, Ritchie B, Shapiro R, Soteres D, Banerji A, Cancian M, Johnston DT, Craig TJ, Launay D, Li HH, Liebhaber M, Nickel T, Offenberger J, Rae W, Schrijvers R, Triggiani M, Wedner HJ, Dobo S, Cornpropst M, Clemons D, Fang L, Collis P, Sheridan WP, Maurer M. Evaluation of avoralstat, an oral kallikrein inhibitor, in a Phase 3 hereditary angioedema prophylaxis trial: The OPuS-2 study. Allergy. 2018 Sep;73(9):1871-1880. doi: 10.1111/all.13466. Epub 2018 Jun 17. PMID: 29688579; PMCID: PMC6175137.