Ziconotide acetate (SNX-111 acetate) is a bioactive peptide that is a potent and specific antagonist blocker of N-type calcium channels. Ziconotide acetate reduces synaptic transmission and may be used in chronic pain research.

Physicochemical Properties

Molecular Formula	C104H176N36O34S7
Molecular Weight	2699.18605232239
Exact Mass	2698.122
CAS #	914454-03-8
Related CAS #	Ziconotide;107452-89-1;Ziconotide TFA
PubChem CID	72941949
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	43
Hydrogen Bond Acceptor Count	48
Rotatable Bond Count	40
Heavy Atom Count	181
Complexity	5510
Defined Atom Stereocenter Count	22
SMILES	C(=O)(O)C.C(C1C=CC(O)=CC=1)[C@@H]1NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H]2NC([C@@H](NC([C@@H](NC(CNC([C@@H](NC(CNC([C@@H](NC([C@H](CSSC[C@H]3C(N[C@H](C(NCC(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(NCC(N[C@H](C(N[C@@H](CSSCC(C(N3)=O)NC(=O)[C@H](CC(=O)O)NC1=O)C(=O)N)=O)CCCCN)=O)=O)CO)=O)CCCNC(N)=N)=O)CSSC2)=O)CO)=O)=O)[C@H](O)C)=O)N)=O)CCCCN)=O)=O)CCCCN)=O)=O)C)=O)CCCCN)=O
InChi Key	LBACTXHPMJIKTR-XZSNVYKZSA-N
InChi Code	InChI=1S/C102H172N36O32S7.C2H4O2/c1-50(2)34-63-91(161)127-62(26-33-171-5)90(160)129-64(35-53-22-24-54(143)25-23-53)92(162)130-65(36-78(148)149)93(163)135-72-48-175-173-45-69(80(108)150)133-86(156)58(18-8-12-29-105)121-76(146)39-117-85(155)66(41-139)131-88(158)61(21-15-32-114-102(111)112)126-96(166)70-46-176-177-47-71(97(167)132-68(43-141)95(165)125-60(87(157)128-63)20-14-31-113-101(109)110)134-89(159)59(19-9-13-30-106)123-81(151)51(3)119-74(144)37-115-83(153)56(16-6-10-27-103)120-75(145)38-116-84(154)57(17-7-11-28-104)124-82(152)55(107)44-172-174-49-73(137-98(72)168)99(169)138-79(52(4)142)100(170)118-40-77(147)122-67(42-140)94(164)136-70;1-2(3)4/h22-25,50-52,55-73,79,139-143H,6-21,26-49,103-107H2,1-5H3,(H2,108,150)(H,115,153)(H,116,154)(H,117,155)(H,118,170)(H,119,144)(H,120,145)(H,121,146)(H,122,147)(H,123,151)(H,124,152)(H,125,165)(H,126,166)(H,127,161)(H,128,157)(H,129,160)(H,130,162)(H,131,158)(H,132,167)(H,133,156)(H,134,159)(H,135,163)(H,136,164)(H,137,168)(H,138,169)(H,148,149)(H4,109,110,113)(H4,111,112,114);1H3,(H,3,4)/t51-,52+,55-,56-,57-,58-,59-,60-,61-,62-,63-,64-,65-,66-,67-,68-,69-,70-,71-,72-,73-,79-;/m0./s1
Chemical Name	acetic acid;2-[(1R,4S,7S,13S,16R,21R,24S,27S,30S,33S,36S,39S,42R,45S,48S,54S,60S,63R,68R,71S,77S)-63-amino-13,45,54,60-tetrakis(4-aminobutyl)-4,36-bis(3-carbamimidamidopropyl)-16-carbamoyl-71-[(1R)-1-hydroxyethyl]-7,39,77-tris(hydroxymethyl)-27-[(4-hydroxyphenyl)methyl]-48-methyl-33-(2-methylpropyl)-30-(2-methylsulfanylethyl)-2,5,8,11,14,23,26,29,32,35,38,41,44,47,50,53,56,59,62,69,72,75,78,85-tetracosaoxo-18,19,65,66,81,82-hexathia-3,6,9,12,15,22,25,28,31,34,37,40,43,46,49,52,55,58,61,70,73,76,79,84-tetracosazatricyclo[40.37.4.221,68]pentaoctacontan-24-yl]acetic 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 (e.g. under nitrogen), avoid exposure to moisture and light.
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

Targets	N-type calcium channel
ln Vitro	Ziconotide acetate only partially suppresses high-voltage-activated calcium currents in differentiated human neuroblastoma IMR32 cells, rat superior cervical ganglion neurons, and rat hippocampus neurons because most native cells have a range of distinct calcium channels. Additionally, ziconotine acetate decreases calcium currents that arise from HEK cells, tsa-201 cells, and Xenopus laevis oocytes expressing the α1B subunit[1]. By limiting the production of pronociceptive neurotransmitters in the spinal cord's dorsal horn, ziconide acetate inhibits the transmission of pain signals, which is how it exerts its antinociceptive action[1].
ln Vivo	In a mouse model of experimental autoimmune encephalomyelitis (EAE), ziconotate (it; 25-100 pmol/site; 5 μL; on the 4th, 10th, 15th, 20th, and 24th days) acetate decreases IL-1β and IL-23 levels in the CNS and splenic production of IL-17 25 days after MOG35-55-elicited EAE[2].
Animal Protocol	Animal/Disease Models: Female C57BL/6mice (18-22 g, 6- 8 weeks old) injected with myelin oligodendrocytes glycoprotein[2] Doses: 25 pmol/site, 50 pmol/site, 100 pmol/site Route of Administration: Intrathecal injection; on the 4th, 10th, 15th, 20th, and 24th days Experimental Results: Dramatically decreased the mechanical hypersensitivity in animals with EAE.
References	[1]. Ziconotide: a review of its pharmacology and use in the treatment of pain. Neuropsychiatr Dis Treat. 2007 Feb;3(1):69-85. [2]. Beneficial Effects of the Calcium Channel Blocker CTK 01512-2 in a Mouse Model of Multiple Sclerosis. Mol Neurobiol. 2018 Dec;55(12):9307-9327.
Additional Infomation	See also: Ziconotide Acetate (annotation moved to).

Solubility Data

Solubility (In Vitro)

H2O: 100 mg/mL DMSO: 25 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (Infinity mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (Infinity mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (Infinity mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 50 mg/mL (Infinity mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	0.3705 mL	1.8524 mL	3.7048 mL
	5 mM	0.0741 mL	0.3705 mL	0.7410 mL
	10 mM	0.0370 mL	0.1852 mL	0.3705 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.