Cyclotraxin B

Cyclotraxin B

Clinical data
ATC code	None
Identifiers
IUPAC name (3S,6R,11R,17S,20S,23S,26S,32S,35S)-6-Amino-20-(4-aminobutyl)-3-(2-amino-2-oxoethyl)-17-(2-carboxyethyl)-23-[(1R)-1-hydroxyethyl]-26-[(4-hydroxyphenyl)methyl]-32-(2-methylsulfanylethyl)-2,5,13,16,19,22,25,28,31,34-decaoxo-8,9-dithia-1,4,12,15,18,21,24,27,30,33-decazabicyclo[33.3.0]octatriacontane-11-carboxylic acid
CAS Number	1203586-72-4
PubChem (CID)	90489002
ChemSpider	29785020
Chemical and physical data
Formula	C48H73N13O17S3
Molar mass	1200.36512 g/mol
3D model (Jmol)	Interactive image
SMILES CC(C1C(=O)NC(C(=O)NC(C(=O)NCC(=O)NC(CSSCC(C(=O)NC(C(=O)N2CCCC2C(=O)NC(C(=O)NCC(=O)NC(C(=O)N1)CC3=CC=C(C=C3)O)CCSC)CC(=O)N)N)C(=O)O)CCC(=O)O)CCCCN)O
InChI InChI=1S/C48H73N13O17S3/c1-24(62)39-46(75)58-28(6-3-4-15-49)43(72)56-29(12-13-38(67)68)41(70)52-21-37(66)55-33(48(77)78)23-81-80-22-27(50)40(69)59-32(19-35(51)64)47(76)61-16-5-7-34(61)45(74)57-30(14-17-79-2)42(71)53-20-36(65)54-31(44(73)60-39)18-25-8-10-26(63)11-9-25/h8-11,24,27-34,39,62-63H,3-7,12-23,49-50H2,1-2H3,(H2,51,64)(H,52,70)(H,53,71)(H,54,65)(H,55,66)(H,56,72)(H,57,74)(H,58,75)(H,59,69)(H,60,73)(H,67,68)(H,77,78)/t24-,27+,28+,29+,30+,31+,32+,33+,34+,39+/m1/s1 Key:JLBMMJHZUYBFGX-ZHTCEXBHSA-N

Cyclotraxin B (CTX-B) is a small (1200 Da) cyclic peptide and highly potent, selective, non-competitive antagonist or negative allosteric modulator of TrkB (IC₅₀  = 0.30 nM),^[1][2] the main receptor of brain-derived neurotrophic factor (BDNF), which itself was derived from BDNF.^[1][3] It crosses the blood-brain-barrier with systemic administration and produces anxiolytic-like effects in animals, though notably not antidepressant-like effects.^[1][4] The compound has also been found to produce analgesic effects in animal models of neuropathic pain.^[5] In addition to TrkB, CTX-B has been found to be an allosteric modulator of VEGFR2, one of the receptors of vascular endothelial growth factor (VEGF).^[2]

See also

• ANA-12
• K252a
• LM22A-4
• 7,8-Dihydroxyflavone
• Deoxygedunin
• HIOC

References

1. Cazorla, Maxime; Jouvenceau, Anne; Rose, Christiane; Guilloux, Jean-Philippe; Pilon, Catherine; Dranovsky, Alex; Prémont, Joël (2010). "Cyclotraxin-B, the First Highly Potent and Selective TrkB Inhibitor, Has Anxiolytic Properties in Mice". PLoS ONE. 5 (3): e9777. doi:10.1371/journal.pone.0009777. ISSN 1932-6203. Missing |last1= in Authors list (help)
2. De Smet, Frederik; Christopoulos, Arthur; Carmeliet, Peter (2014). "Allosteric targeting of receptor tyrosine kinases". Nature Biotechnology. 32 (11): 1113–1120. doi:10.1038/nbt.3028. ISSN 1087-0156.
3. Growth Factor Receptors—Advances in Research and Application: 2013 Edition. ScholarlyEditions. 21 June 2013. pp. 42–. ISBN 978-1-4816-7619-9.
4. Advances in Physiology Research and Application: 2011 Edition. ScholarlyEditions. 9 January 2012. pp. 1431–. ISBN 978-1-4649-2075-2.
5. Constandil, Luis; Goich, Mariela; Hernández, Alejandro; Bourgeais, Laurence; Cazorla, Maxime; Hamon, Michel; Villanueva, Luis; Pelissier, Teresa (2012). "Cyclotraxin-B, a New TrkB Antagonist, and Glial Blockade by Propentofylline, Equally Prevent and Reverse Cold Allodynia Induced by BDNF or Partial Infraorbital Nerve Constriction in Mice". The Journal of Pain. 13 (6): 579–589. doi:10.1016/j.jpain.2012.03.008. ISSN 1526-5900.