Tat-NR2B9c TFA (Tat-NR2Bct TFA) is an inhibitor (blocker/antagonist) of PSD-95, with EC50s of 6.7 nM and 670 nM for PSD-95d2 (PSD-95 PDZ domain 2) and PSD-95d1, respectively. Tat-NR2B9c TFA disrupts the PSD-95/NMDAR interaction and inhibits/disrupts the binding of PSD-95 to NR2A and NR2B with IC50s of 0.5 μM and 8 μM, respectively. Tat-NR2B9c TFA can also inhibit neuronal nitric oxide synthase (nNOS)/PSD-95 interaction and has neuro-protective (neuro-protection) effects.

Physicochemical Properties

Molecular Formula	C107H189F3N42O32
Molecular Weight	2632.90299105644
Exact Mass	2518.451
CAS #	1834571-04-8
Related CAS #	Tat-NR2B9c;500992-11-0
PubChem CID	44568939
Appearance	White to off-white solid powder
LogP	-19.3
Hydrogen Bond Donor Count	49
Hydrogen Bond Acceptor Count	40
Rotatable Bond Count	99
Heavy Atom Count	177
Complexity	5380
Defined Atom Stereocenter Count	20
SMILES	C(F)(F)(F)C(=O)O.[C@H](CCCNC(N)=N)(C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)O)C(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)CNC(=O)[C@@H](N)CC1C=CC(O)=CC=1
InChi Key	XWQVQFBTSBCKLI-FKXNDIMNSA-N
InChi Code	InChI=1S/C105H188N42O30/c1-7-55(6)80(98(175)140-69(34-36-77(154)155)92(169)143-72(50-148)95(172)142-71(48-78(156)157)94(171)146-79(54(4)5)99(176)177)147-97(174)74(52-150)145-96(173)73(51-149)144-93(170)70(46-53(2)3)141-90(167)62(22-10-13-39-108)133-85(162)63(24-15-41-124-101(113)114)135-87(164)65(26-17-43-126-103(117)118)136-88(165)66(27-18-44-127-104(119)120)138-91(168)68(33-35-75(110)152)139-89(166)67(28-19-45-128-105(121)122)137-86(163)64(25-16-42-125-102(115)116)134-84(161)61(21-9-12-38-107)132-83(160)60(20-8-11-37-106)131-82(159)59(23-14-40-123-100(111)112)130-76(153)49-129-81(158)58(109)47-56-29-31-57(151)32-30-56/h29-32,53-55,58-74,79-80,148-151H,7-28,33-52,106-109H2,1-6H3,(H2,110,152)(H,129,158)(H,130,153)(H,131,159)(H,132,160)(H,133,162)(H,134,161)(H,135,164)(H,136,165)(H,137,163)(H,138,168)(H,139,166)(H,140,175)(H,141,167)(H,142,172)(H,143,169)(H,144,170)(H,145,173)(H,146,171)(H,147,174)(H,154,155)(H,156,157)(H,176,177)(H4,111,112,123)(H4,113,114,124)(H4,115,116,125)(H4,117,118,126)(H4,119,120,127)(H4,121,122,128)/t55-,58-,59-,60-,61-,62-,63-,64-,65-,66-,67-,68-,69-,70-,71-,72-,73-,74-,79-,80-/m0/s1
Chemical Name	(4S)-4-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]hexanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-methylpentanoyl]amino]-5-[[(2S)-1-[[(2S)-3-carboxy-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-5-oxopentanoic acid
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	Tat-NR2B9c, a PSD-95 benchmark, exhibits domain affinity in comparison to PSD-95d1 (EC 50, 0.67 μM) with an EC50 of 6.7 nM for PSD-95d2. With an IC50 of 0.5 μM, approximately 8 μM, and 0.75 μM, respectively, Tat-NR2B9c inhibits the binding of NMDAR2A, NMDAR2B, and NMDAR2C to PSD-95. Moreover, Tat-NR2B9c, with an IC50 of around 0.2 μM, inhibits the PSD-95 and nNOS interaction [1]. While NMDA-induced p38 activation in YAC128 striatum is reduced by around 50% when Tat-NR2B9c lowers PSD-95 binding to GluN2B in YAC128 striatum, NMDA-induced JNK activation is unaffected [2].
ln Vivo	Tat-NR2B9c (10 nmol/g, iv) did not affect infarct volume at 3 nmol/g, but it did diminish it with C57BL/6 nozzles [3].
References	[1]. PDZ protein interactions underlying NMDA receptor-mediated excitotoxicity and neuroprotection by PSD-95 inhibitors. J Neurosci. 2007 Sep 12;27(37):9901-15. [2]. P38 MAPK is involved in enhanced NMDA receptor-dependent excitotoxicity in YAC transgenic mouse model of Huntington disease. Neurobiol Dis. 2012 Mar;45(3):999-1009.
Additional Infomation	Na 1 is under investigation in clinical trial NCT00728182 (Evaluating Neuroprotection in Aneurysm Coiling Therapy).

Solubility Data

Solubility (In Vitro)	H2O : ≥ 50 mg/mL (~18.99 mM)
Solubility (In Vivo)	Solubility in Formulation 1: 100 mg/mL (37.98 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	0.3798 mL	1.8990 mL	3.7981 mL
	5 mM	0.0760 mL	0.3798 mL	0.7596 mL
	10 mM	0.0380 mL	0.1899 mL	0.3798 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.