KN62 | CAS#127191-97-3 | P2X7R antagonist

MedKoo Cat#: 406815 | Name: KN62

Description:

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

KN62 is a P2X7R antagonist (hP2X7 IC50 = 51 nM) and Ca2+/calmodulin-dependent protein kinase II inhibitor. KN62 inhibits the invasiveness of cancer cells in vitro and in vivo KN62 causes retrograde amnesia in the rat. KN62 attenuates glutamate release by inhibiting voltage-dependent Ca(2+)-channels. The effect of KN62 on Ca(2+)-influx appears to be specific to slowly-or non-inactivating conductances, and therefore presents KN62 as a potentially useful tool.

Chemical Structure

KN62

CAS#127191-97-3 (free base)

Theoretical Analysis

MedKoo Cat#: 406815

Name: KN62

CAS#: 127191-97-3 (free base)

Chemical Formula: C38H35N5O6S2

Exact Mass: 721.2029

Molecular Weight: 721.85

Elemental Analysis: C, 63.23; H, 4.89; N, 9.70; O, 13.30; S, 8.88

Price and Availability

Size	Price	Availability
10mg	USD 350.00	2 Weeks
25mg	USD 550.00	2 Weeks
50mg	USD 950.00	2 Weeks
100mg	USD 1,650.00	2 Weeks
200mg	USD 2,650.00	2 Weeks

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Related CAS #

No Data

Synonym

KN62; KN-62; KN 62.

IUPAC/Chemical Name

(S)-4-(2-(N-methylisoquinoline-5-sulfonamido)-3-oxo-3-(4-phenylpiperazin-1-yl)propyl)phenyl isoquinoline-5-sulfonate

InChi Key

RJVLFQBBRSMWHX-DHUJRADRSA-N

InChi Code

InChI=1S/C38H35N5O6S2/c1-41(50(45,46)36-11-5-7-29-26-39-19-17-33(29)36)35(38(44)43-23-21-42(22-24-43)31-9-3-2-4-10-31)25-28-13-15-32(16-14-28)49-51(47,48)37-12-6-8-30-27-40-20-18-34(30)37/h2-20,26-27,35H,21-25H2,1H3/t35-/m0/s1

SMILES Code

CN([C@@H](CC1=CC=C(OS(=O)(C2=C3C(C=NC=C3)=CC=C2)=O)C=C1)C(N4CCN(C5=CC=CC=C5)CC4)=O)S(C6=CC=CC7=C6C=CN=C7)(=O)=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

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

Related CAS# 127191-97-3 (KN62 free base)

Product Data

Product Data

Instruction

View handling instruction

Biological target:

KN-62 is a selective and reversible inhibitor of calmodulin-dependent protein kinase II (CaMK-II) with a Ki of 0.9 μM for rat brain CaMK-II.

In vitro activity:

KN-62 potently antagonized ATP-stimulated Ba2+ influx into fura-2 loaded human lymphocytes with an IC50 of 12.7 +/- 1.5 nM (n = 3) and complete inhibition of the flux at a concentration of 500 nM. Similarly, KN-62 inhibited ATP-stimulated ethidium+ uptake, measured by time resolved flow cytometry, with an IC50 of 13.1 +/- 2.6 nM (n = 4) and complete inhibition of the flux at 500 nM. Reference: Br J Pharmacol. 1997 Apr;120(8):1483-90. https://pubmed.ncbi.nlm.nih.gov/9113369/

In vivo activity:

Immediate post-training intra-hippocampal administration of the calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitor KN-62 (3.6 ng/side) attenuated memory of the water-finding task, but not that of the habituation acquired concomitantly. However, when the habituation was carried out alone in the absence of the water-finding task, its retention was inhibited by KN-62. Reference: Behav Pharmacol. 1999 Feb;10(1):99-104. https://pubmed.ncbi.nlm.nih.gov/10780306/

	Solvent	mg/mL	mM
Solubility
	DMF	30.0	41.56
	DMF:PBS (pH 7.2) (1:2)	0.3	0.42
	DMSO	75.6	104.66
	Ethanol	1.0	1.39

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 721.85 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

Formulation protocol:

1. Gargett CE, Wiley JS. The isoquinoline derivative KN-62 a potent antagonist of the P2Z-receptor of human lymphocytes. Br J Pharmacol. 1997 Apr;120(8):1483-90. doi: 10.1038/sj.bjp.0701081. PMID: 9113369; PMCID: PMC1564633. 2. Minami H, Inoue S, Hidaka H. The effect of KN-62, Ca2+/calmodulin dependent protein kinase II inhibitor on cell cycle. Biochem Biophys Res Commun. 1994 Feb 28;199(1):241-8. doi: 10.1006/bbrc.1994.1220. PMID: 8123019. 3. Wolfman C, Izquierdo LA, Schröder N, Izquierdo I. Intra-hippocampal KN-62 hinders the memory of habituation acquired alone, but not simultaneously with a water-finding task. Behav Pharmacol. 1999 Feb;10(1):99-104. doi: 10.1097/00008877-199902000-00009. PMID: 10780306. 4. Schnabel R, Palmer MJ, Kilpatrick IC, Collingridge GL. A CaMKII inhibitor, KN-62, facilitates DHPG-induced LTD in the CA1 region of the hippocampus. Neuropharmacology. 1999 Apr;38(4):605-8. doi: 10.1016/s0028-3908(98)00229-9. PMID: 10221764.

In vitro protocol:

In vivo protocol:

1. Wolfman C, Izquierdo LA, Schröder N, Izquierdo I. Intra-hippocampal KN-62 hinders the memory of habituation acquired alone, but not simultaneously with a water-finding task. Behav Pharmacol. 1999 Feb;10(1):99-104. doi: 10.1097/00008877-199902000-00009. PMID: 10780306. 2. Schnabel R, Palmer MJ, Kilpatrick IC, Collingridge GL. A CaMKII inhibitor, KN-62, facilitates DHPG-induced LTD in the CA1 region of the hippocampus. Neuropharmacology. 1999 Apr;38(4):605-8. doi: 10.1016/s0028-3908(98)00229-9. PMID: 10221764.

1: Park JH, Lee GE, Lee SD, Hien TT, Kim S, Yang JW, Cho JH, Ko H, Lim SC, Kim YG, Kang KW, Kim YC. Discovery of novel 2,5-dioxoimidazolidine-based P2X(7) receptor antagonists as constrained analogues of KN62. J Med Chem. 2015 Mar 12;58(5):2114-34. doi: 10.1021/jm500324g. Epub 2015 Feb 23. PubMed PMID: 25597334. 2: Baraldi PG, Makaeva R, Pavani MG, Nuñez Mdel C, Spalluto G, Moro S, Falzoni S, Di Virgilio F, Romagnoli R. Synthesis, biological activity and molecular modeling studies of 1,2,3,4-tetrahydroisoquinoline derivatives as conformationally constrained analogues of KN62, a potent antagonist of the P2X7-receptor containing a tyrosine moiety. Arzneimittelforschung. 2002;52(4):273-85. PubMed PMID: 12040970. 3: Baraldi PG, Romagnoli R, Tabrizi MA, Falzoni S, di Virgilio F. Synthesis of conformationally constrained analogues of KN62, a potent antagonist of the P2X7-receptor. Bioorg Med Chem Lett. 2000 Apr 3;10(7):681-4. PubMed PMID: 10762053. 4: Enns L, Murray D, Mirzayans R. Effects of the protein kinase inhibitors wortmannin and KN62 on cellular radiosensitivity and radiation-activated S phase and G1/S checkpoints in normal human fibroblasts. Br J Cancer. 1999 Nov;81(6):959-65. PubMed PMID: 10576651; PubMed Central PMCID: PMC2362948. 5: Marley PD, Thomson KA. The Ca++/calmodulin-dependent protein kinase II inhibitors KN62 and KN93, and their inactive analogues KN04 and KN92, inhibit nicotinic activation of tyrosine hydroxylase in bovine chromaffin cells. Biochem Biophys Res Commun. 1996 Apr 5;221(1):15-8. PubMed PMID: 8660326. 6: Sihra TS, Pearson HA. Ca/calmodulin-dependent kinase II inhibitor KN62 attenuates glutamate release by inhibiting voltage-dependent Ca(2+)-channels. Neuropharmacology. 1995 Jul;34(7):731-41. PubMed PMID: 8532140. 7: Clyne CD, Nguyen A, Rainey WE. The effects of KN62, a Ca2+/calmodulin-dependent protein kinase II inhibitor, on adrenocortical cell aldosterone production. Endocr Res. 1995 Feb-May;21(1-2):259-65. PubMed PMID: 7588388. 8: Wolfman C, Fin C, Dias M, Bianchin M, Da Silva RC, Schmitz PK, Medina JH, Izquierdo I. Intrahippocampal or intraamygdala infusion of KN62, a specific inhibitor of calcium/calmodulin-dependent protein kinase II, causes retrograde amnesia in the rat. Behav Neural Biol. 1994 May;61(3):203-5. PubMed PMID: 8067974.