A1899
new
featured

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

MedKoo CAT#: 563499

CAS#: 498577-46-1

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

Chemical Structure

img
A1899
CAS# 498577-46-1
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 563499
Name: A1899
CAS#: 498577-46-1
Chemical Formula: C30H26F2N2O3
Exact Mass: 500.19
Molecular Weight: 500.540
Elemental Analysis: C, 71.99; H, 5.24; F, 7.59; N, 5.60; O, 9.59

Price and Availability

Size Price Availability Quantity
100mg USD 750 2 Weeks
200mg USD 1250 2 Weeks
1g USD 2950 2 Weeks
2g USD 5250 2 Weeks
Bulk inquiry

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

More Info:

Product Data:
Product Data
Instruction:
View handling instruction
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 50.1 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

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

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.


2: 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. PMID: 28494157.


3: 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. PMID: 23460565; PMCID: PMC3865919.


4: 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. PMID: 21914059.


5: 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. PMID: 26268529; PMCID: PMC4613942.


6: 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. PMID: 21362619; PMCID: PMC3077598.


7: 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. PMID: 18939932.


8: Malde O, Cross C, Lim CL, Marghoub A, Cunningham ML, Hopper RA, Moazen M. Predicting calvarial morphology in sagittal craniosynostosis. Sci Rep. 2020 Jan 8;10(1):3. doi: 10.1038/s41598-019-55224-5. PMID: 31913294; PMCID: PMC6949270.


9: 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. PMID: 21181919.


10: 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. PMID: 24932805; PMCID: PMC4164933.


11: Wiedmann F, Kiper AK, Bedoya M, Ratte A, Rinné S, Kraft M, Waibel M, Anad P, Wenzel W, González W, Katus HA, Decher N, Schmidt C. Identification of the A293 (AVE1231) Binding Site in the Cardiac Two-Pore-Domain Potassium Channel TASK-1: a Common Low Affinity Antiarrhythmic Drug Binding Site. Cell Physiol Biochem. 2019;52(5):1223-1235. doi: 10.33594/000000083. PMID: 31001961.


12: 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. PMID: 22977011.


13: 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. PMID: 21390140; PMCID: PMC3042648.


14: 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. PMID: 25849724; PMCID: PMC4415209.


15: Gurges P, Liu H, Horner RL. Modulation of TASK-1/3 channels at the hypoglossal motoneuron pool and effects on tongue motor output and responses to excitatory inputs in vivo: implications for strategies for obstructive sleep apnea pharmacotherapy. Sleep. 2021 Jan 21;44(1):zsaa144. doi: 10.1093/sleep/zsaa144. PMID: 32745213; PMCID: PMC7819847.


16: 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. PMID: 25511502.


17: Buzi C, Profico A, Liang C, Khonsari RH, O'Higgins P, Moazen M, Harvati K. Icex: Advances in the automatic extraction and volume calculation of cranial cavities. J Anat. 2023 Jun;242(6):1172-1183. doi: 10.1111/joa.13843. Epub 2023 Feb 11. PMID: 36774197; PMCID: PMC10184549.


18: Guarina L, Vandael DH, Carabelli V, Carbone E. Low pHo 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. PMID: 28026020; PMCID: PMC5390891.


19: Cross C, Delye H, Khonsari RH, Moazen M. A preliminary analysis of replicating the biomechanics of helmet therapy for sagittal craniosynostosis. Childs Nerv Syst. 2023 Apr;39(4):989-996. doi: 10.1007/s00381-022-05792-1. Epub 2022 Dec 24. PMID: 36565313; PMCID: PMC10160196.


20: Ramírez D, Mejia-Gutierrez M, Insuasty B, Rinné S, Kiper AK, Platzk M, Müller T, Decher N, Quiroga J, De-la-Torre P, González W. 5-(Indol-2-yl)pyrazolo[3,4-b]pyridines as a New Family of TASK-3 Channel Blockers: A Pharmacophore-Based Regioselective Synthesis. Molecules. 2021 Jun 25;26(13):3897. doi: 10.3390/molecules26133897. PMID: 34202296; PMCID: PMC8271858.