A1899
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MedKoo CAT#: 563499

CAS#: 498577-46-1

Description: A1899 is a potent and selective TASK-1 and TASK-3 antagonist.


Chemical Structure

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A1899
CAS# 498577-46-1

Theoretical Analysis

MedKoo Cat#: 563499
Name: A1899
CAS#: 498577-46-1
Chemical Formula: C30H26F2N2O3
Exact Mass: 500.1911
Molecular Weight: 500.54
Elemental Analysis: C, 71.99; H, 5.24; F, 7.59; N, 5.60; O, 9.59

Price and Availability

Size Price Availability Quantity
10.0mg USD 340.0 2 Weeks
25.0mg USD 640.0 2 Weeks
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Synonym: A1899; A-1899; A 1899; S20951; S-20951; S 20951;

IUPAC/Chemical Name: N-(2,4-difluorobenzyl)-2'-((2-(4-methoxyphenyl)acetamido)methyl)-[1,1'-biphenyl]-2-carboxamide

InChi Key: IXKPEYHRIVQTCU-UHFFFAOYSA-N

InChi Code: InChI=1S/C30H26F2N2O3/c1-37-24-14-10-20(11-15-24)16-29(35)33-18-21-6-2-3-7-25(21)26-8-4-5-9-27(26)30(36)34-19-22-12-13-23(31)17-28(22)32/h2-15,17H,16,18-19H2,1H3,(H,33,35)(H,34,36)

SMILES Code: O=C(C1=CC=CC=C1C2=CC=CC=C2CNC(CC3=CC=C(OC)C=C3)=O)NCC4=CC=C(F)C=C4F

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: >3 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: 2934.99.03.00

Product Data:

Biological target: A1899 is a potent K2P3.1 (TASK-1) and K2P9.1 (TASK-3) channel blocker (IC50 values are 7 nM and 70 nM for human TASK-1 and TASK-3 expressed in CHO cells, respectively).
In vitro activity: In cell attached patches in type‐1 cells 400 nmol/L A1899 caused a rapid and reversible inhibition of TASK channel activity by 34 ± 7% (n = 8; P = 0.028; Fig. 4A and B). A similar level of inhibition was also seen at a lower concentration of 50 nmol/L and a substantive further increase in inhibition at 4000 nmol/L to over 60% (see Fig. 4C). Figure 4D presents a representative all‐points histogram which shows that at 400 nmol/L A1899 causes an inhibition of TASK channel activity across all conductance levels. Reference: Physiol Rep. 2018 Sep; 6(19): e13876. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170881/
In vivo activity: TBD

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 50.05 99.99

Preparing Stock Solutions

The following data is based on the product molecular weight 500.54 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. O'Donohoe PB, Huskens N, Turner PJ, Pandit JJ, Buckler KJ. A1899, PK-THPP, ML365, and Doxapram inhibit endogenous TASK channels and excite calcium signaling in carotid body type-1 cells. Physiol Rep. 2018 Sep;6(19):e13876. doi: 10.14814/phy2.13876. PMID: 30284397; PMCID: PMC6170881.
In vitro protocol: 1. O'Donohoe PB, Huskens N, Turner PJ, Pandit JJ, Buckler KJ. A1899, PK-THPP, ML365, and Doxapram inhibit endogenous TASK channels and excite calcium signaling in carotid body type-1 cells. Physiol Rep. 2018 Sep;6(19):e13876. doi: 10.14814/phy2.13876. PMID: 30284397; PMCID: PMC6170881.
In vivo protocol: TBD

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1: Ramírez D, Arévalo B, Martínez G, Rinné S, Sepúlveda FV, Decher N, González W. Side Fenestrations Provide an "Anchor" for a Stable Binding of A1899 to the Pore of TASK-1 Potassium Channels. Mol Pharm. 2017 Jul 3;14(7):2197-2208. doi: 10.1021/acs.molpharmaceut.7b00005. Epub 2017 May 30. PubMed PMID: 28494157.

2: Guarina L, Vandael DH, Carabelli V, Carbone E. Low pH(o) boosts burst firing and catecholamine release by blocking TASK-1 and BK channels while preserving Cav1 channels in mouse chromaffin cells. J Physiol. 2017 Apr 15;595(8):2587-2609. doi: 10.1113/JP273735. Epub 2017 Mar 2. PubMed PMID: 28026020; PubMed Central PMCID: PMC5390891.

3: Chokshi RH, Larsen AT, Bhayana B, Cotten JF. Breathing Stimulant Compounds Inhibit TASK-3 Potassium Channel Function Likely by Binding at a Common Site in the Channel Pore. Mol Pharmacol. 2015 Nov;88(5):926-34. doi: 10.1124/mol.115.100107. Epub 2015 Aug 12. PubMed PMID: 26268529; PubMed Central PMCID: PMC4613942.

4: Dadi PK, Luo B, Vierra NC, Jacobson DA. TASK-1 Potassium Channels Limit Pancreatic α-Cell Calcium Influx and Glucagon Secretion. Mol Endocrinol. 2015 May;29(5):777-87. doi: 10.1210/me.2014-1321. Epub 2015 Apr 7. PubMed PMID: 25849724; PubMed Central PMCID: PMC4415209.

5: Kiper AK, Rinné S, Rolfes C, Ramírez D, Seebohm G, Netter MF, González W, Decher N. Kv1.5 blockers preferentially inhibit TASK-1 channels: TASK-1 as a target against atrial fibrillation and obstructive sleep apnea? Pflugers Arch. 2015 May;467(5):1081-90. doi: 10.1007/s00424-014-1665-1. Epub 2014 Dec 17. PubMed PMID: 25511502.

6: Dadi PK, Vierra NC, Jacobson DA. Pancreatic β-cell-specific ablation of TASK-1 channels augments glucose-stimulated calcium entry and insulin secretion, improving glucose tolerance. Endocrinology. 2014 Oct;155(10):3757-68. doi: 10.1210/en.2013-2051. Epub 2014 Jun 16. PubMed PMID: 24932805; PubMed Central PMCID: PMC4164933.

7: Cotten JF. TASK-1 (KCNK3) and TASK-3 (KCNK9) tandem pore potassium channel antagonists stimulate breathing in isoflurane-anesthetized rats. Anesth Analg. 2013 Apr;116(4):810-6. doi: 10.1213/ANE.0b013e318284469d. Epub 2013 Mar 4. PubMed PMID: 23460565; PubMed Central PMCID: PMC3865919.

8: Schiekel J, Lindner M, Hetzel A, Wemhöner K, Renigunta V, Schlichthörl G, Decher N, Oliver D, Daut J. The inhibition of the potassium channel TASK-1 in rat cardiac muscle by endothelin-1 is mediated by phospholipase C. Cardiovasc Res. 2013 Jan 1;97(1):97-105. doi: 10.1093/cvr/cvs285. Epub 2012 Sep 12. PubMed PMID: 22977011.

9: Zheng JX, Zeng Z, Zheng YY, Yin SJ, Zhang DY, Yu YY, Wang F. Role of hepatitis B virus base core and precore/core promoter mutations on hepatocellular carcinoma in untreated older genotype C Chinese patients. J Viral Hepat. 2011 Oct;18(10):e423-31. doi: 10.1111/j.1365-2893.2011.01458.x. Epub 2011 Apr 4. PubMed PMID: 21914059.

10: Utama A, Siburian MD, Purwantomo S, Intan MD, Kurniasih TS, Gani RA, Achwan WA, Arnelis, Lelosutan SA, Lukito B, Harmono T, Zubir N, Julius, Soemohardjo S, Lesmana LA, Sulaiman A, Tai S. Association of core promoter mutations of hepatitis B virus and viral load is different in HBeAg(+) and HBeAg(-) patients. World J Gastroenterol. 2011 Feb 14;17(6):708-16. doi: 10.3748/wjg.v17.i6.708. PubMed PMID: 21390140; PubMed Central PMCID: PMC3042648.

11: Streit AK, Netter MF, Kempf F, Walecki M, Rinné S, Bollepalli MK, Preisig-Müller R, Renigunta V, Daut J, Baukrowitz T, Sansom MS, Stansfeld PJ, Decher N. A specific two-pore domain potassium channel blocker defines the structure of the TASK-1 open pore. J Biol Chem. 2011 Apr 22;286(16):13977-84. doi: 10.1074/jbc.M111.227884. Epub 2011 Mar 1. PubMed PMID: 21362619; PubMed Central PMCID: PMC3077598.

12: Biswas A, Banerjee A, Chandra PK, Datta S, Panigrahi R, Dutta D, De BK, Pal M, Guha SK, Chakrabarti S, Chakravarty R. Variations in the functional domain of basal core promoter of hepatitis B virus among Eastern Indian patients with prevalence of genotypes A, C, and D among the same ethnic population. J Med Virol. 2011 Feb;83(2):253-60. doi: 10.1002/jmv.21979. PubMed PMID: 21181919.

13: van Bodegraven AA, van Everdingen JJ, Dijkstra G, de Jong DJ, Oldenburg B, Hommes DW; CBO-werkgroep ‘IBD bij volwassenen'. [Guideline 'Diagnosis and treatment of inflammatory bowel disease in adults'. I. Diagnosis and treatment]. Ned Tijdschr Geneeskd. 2010;154:A1899. Dutch. PubMed PMID: 21029496.

14: Chen CH, Changchien CS, Lee CM, Hung CH, Hu TH, Wang JH, Wang JC, Lu SN. Combined mutations in pre-s/surface and core promoter/precore regions of hepatitis B virus increase the risk of hepatocellular carcinoma: a case-control study. J Infect Dis. 2008 Dec 1;198(11):1634-42. doi: 10.1086/592990. PubMed PMID: 18939932.

15: Tanaka Y, Orito E, Yuen MF, Mukaide M, Sugauchi F, Ito K, Ozasa A, Sakamoto T, Kurbanov F, Lai CL, Mizokami M. Two subtypes (subgenotypes) of hepatitis B virus genotype C: A novel subtyping assay based on restriction fragment length polymorphism. Hepatol Res. 2005 Nov;33(3):216-24. Epub 2005 Oct 28. PubMed PMID: 16257576.

16: Guo Y, Hou J, Luo K, Feng X. Genetic mutations of precore region of hepatitis B virus in hepatitis B e antigen-negative patients with fulminant hepatitis B and translation of precore variants in vitro. Zhonghua Gan Zang Bing Za Zhi. 2001 Feb;9(1):42-4. PubMed PMID: 11242136.

A1899

10.0mg / USD 340.0