TC14012, a plasma-stable model of T140, is a selective CXCR4 antagonist with an IC50 of 19.3 nM. TC14012 is a potent CXCR7 electrolyte that recruits β-arrestin2 to CXCR7 with an EC50 of 350 nM. TC14012 has anti-HIV activity and anti-cancer activity.

Physicochemical Properties

Molecular Formula	C90H140N34O19S2
Molecular Weight	2066.4
Exact Mass	2065.047
CAS #	368874-34-4
Related CAS #	TC14012 TFA
PubChem CID	16130651
Appearance	White to off-white solid powder
LogP	-5.6
Hydrogen Bond Donor Count	35
Hydrogen Bond Acceptor Count	27
Rotatable Bond Count	51
Heavy Atom Count	145
Complexity	4290
Defined Atom Stereocenter Count	14
SMILES	N=C(N)NCCC[C@@H](C(N)=O)NC([C@H]1NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H]2CCCN2C([C@H](NC([C@@H](NC([C@@H](NC([C@@H](NC(=O)[C@H](CSSC1)NC([C@@H](NC([C@@H](NC([C@@H](N)CCCNC(N)=N)=O)CCCNC(N)=N)=O)CC3=CC4=CC=CC=C4C=C3)=O)CC5=CC=C(O)C=C5)=O)CCCNC(N)=O)=O)CCCCN)=O)CCCNC(N)=O)=O)=O)CC6=CC=C(O)C=C6)=O)CCCNC(N)=N)=O)CCCNC(N)=O)=O)=O
InChi Key	SGDDHDBBOJNZKY-LNDHEDFZSA-N
InChi Code	InChI=1S/C90H140N34O19S2/c91-34-4-3-16-58-74(131)118-63(22-11-41-111-90(104)143)83(140)124-42-12-23-69(124)82(139)121-65(45-50-27-32-55(126)33-28-50)78(135)117-60(19-8-38-108-87(100)101)73(130)115-62(21-10-40-110-89(103)142)76(133)122-67(80(137)112-57(70(93)127)17-6-36-106-85(96)97)47-144-145-48-68(81(138)120-64(44-49-25-30-54(125)31-26-49)77(134)116-61(72(129)114-58)20-9-39-109-88(102)141)123-79(136)66(46-51-24-29-52-13-1-2-14-53(52)43-51)119-75(132)59(18-7-37-107-86(98)99)113-71(128)56(92)15-5-35-105-84(94)95/h1-2,13-14,24-33,43,56-69,125-126H,3-12,15-23,34-42,44-48,91-92H2,(H2,93,127)(H,112,137)(H,113,128)(H,114,129)(H,115,130)(H,116,134)(H,117,135)(H,118,131)(H,119,132)(H,120,138)(H,121,139)(H,122,133)(H,123,136)(H4,94,95,105)(H4,96,97,106)(H4,98,99,107)(H4,100,101,108)(H3,102,109,141)(H3,103,110,142)(H3,104,111,143)/t56-,57-,58-,59-,60-,61-,62-,63+,64-,65-,66-,67-,68-,69-/m0/s1
Chemical Name	(3R,6S,9S,12S,15R,20R,23S,26S,29S,32S)-6-(4-aminobutyl)-N-[(2S)-1-amino-5-carbamimidamido-1-oxopentan-2-yl]-15-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]-26-(3-carbamimidamidopropyl)-3,9,23-tris[3-(carbamoylamino)propyl]-12,29-bis[(4-hydroxyphenyl)methyl]-2,5,8,11,14,22,25,28,31-nonaoxo-17,18-dithia-1,4,7,10,13,21,24,27,30-nonazabicyclo[30.3.0]pentatriacontane-20-carboxamide
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

More than 95% of the HXB2 (X4) or 89.6 (ambitropic) strains cannot infect CXCR4-expressing cells when TC14012 (1 mM) is present. In contrast, TC14012 (1 mM) cannot prevent the infection of SF162 (R5) or 89.6 (ambitropic) CCR5-expressing cells. Upon infection with TC14012, U373 cells—which express endogenous CXCR7 but not CXCR4—phosphorylate erk 1/2. CXCR7 and CXCR7-Cter4 chimeras can recruit inhibitory proteins following TC14012 stimulation, while CXCR4 and CXCR4-Cter7 cannot [2].

References

[1]. Development of specific CXCR4 inhibitors possessing high selectivity indexes as well as complete stability in serum based on an anti-HIV peptide T140. Bioorg Med Chem Lett. 2001 Jul 23;11(14):1897-902. [2]. The peptidomimetic CXCR4 antagonist TC14012 recruits beta-arrestin to CXCR7: roles of receptor domains. J Biol Chem. 2010 Dec 3;285(49):37939-43.

Solubility Data

Solubility (In Vitro)

DMSO : ~25 mg/mL (~12.10 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.67 mg/mL (0.81 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 16.7 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: ≥ 1.67 mg/mL (0.81 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 16.7 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: ≥ 1.67 mg/mL (0.81 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 16.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	0.4839 mL	2.4197 mL	4.8393 mL
	5 mM	0.0968 mL	0.4839 mL	0.9679 mL
	10 mM	0.0484 mL	0.2420 mL	0.4839 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.