Targapremir-210 (TGP-210) is a novel potent and selective inhibitor of microRNA-210 with anticancer activity. Targapremir-210 inhibits tumorigenesis in a mouse xenograft model of hypoxic triple negative breast cancer. Targapremir-210 selectively recognizes the miR-210 precursor and can differentially recognize RNAs in cells that have the same target motif but have different expression levels, revealing this important feature for selectively drugging RNAs for the first time. Targapremir-210 inhibits pre-miR-210 processing with high binding affinity (Kd~200 nM).

Physicochemical Properties

Molecular Formula	C32H36N10O2
Molecular Weight	592.694045066834
Exact Mass	592.302
CAS #	1049722-30-6
PubChem CID	44221088
Appearance	Light yellow to yellow solid powder
LogP	3.59
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	12
Heavy Atom Count	44
Complexity	973
Defined Atom Stereocenter Count	0
SMILES	O(CCCC(NCCCN=[N+]=[N-])=O)C1=CC=CC(=C1)C1=NC2=CC=C(C=C2N1)C1=NC2=CC=C(C=C2N1)N1CCN(C)CC1
InChi Key	PAYVJEWMAWLKAP-UHFFFAOYSA-N
InChi Code	InChI=1S/C32H36N10O2/c1-41-14-16-42(17-15-41)24-9-11-27-29(21-24)39-32(37-27)23-8-10-26-28(20-23)38-31(36-26)22-5-2-6-25(19-22)44-18-3-7-30(43)34-12-4-13-35-40-33/h2,5-6,8-11,19-21H,3-4,7,12-18H2,1H3,(H,34,43)(H,36,38)(H,37,39)
Chemical Name	N-(3-Azidopropyl)-4-[3-[6-(4-methyl-1-piperazinyl)[2,6'-bi-1H-benzimidazol]-2'-yl]phenoxy]-butanamide
Synonyms	TGP-210Targapremir-210 TGP 210Targapremir 210 TGP210 Targapremir210
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
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	In MDA-MB-231 cells grown under hypoxic conditions, targapremir-210 decreases the amount of mature miR-210 with an IC50 of approximately 200 nM [1]. MDA-MB-231 cells are specifically induced to undergo apoptosis in hypoxic environments by tigapremir-210 (200 nM). When MDA-MB-231 cells are cultivated in normoxic conditions, tartapremir-210 does not cause apoptosis, but it does when the conditions are hypoxic [1].
ln Vivo	Targapremir-210 (100 μL, 200 nM; intraperitoneal injection once) inhibits triple-negative breast cancer (TNBC) cell growth in MDA-MB-231 in vivo. In TNBC animal models, tartapremir-210 decreases tumor burden and can bind to tumors for up to 21 days [1].
Animal Protocol	Animal/Disease Models: NOD/SCID (severe combined immunodeficient) mouse were subcutaneously (sc) (sc) transplanted with cell suspension into the breast fat pad [1]. Doses: 100 μL, 200 nM Route of Administration: Single intraperitoneal (ip) injection 24 hrs (hrs (hours)) after transplantation Experimental Results: diminished tumor growth as assessed by luciferase signal intensity and quality of resected tumors.
References	[1]. Costales MG, et al. Small Molecule Inhibition of microRNA-210 Reprograms an Oncogenic Hypoxic Circuit. J Am Chem Soc. 2017 Mar 8; 139(9):3446-3455.

Solubility Data

Solubility (In Vitro)

DMSO : ~250 mg/mL (~421.81 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (3.51 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 20.8 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: ≥ 2.08 mg/mL (3.51 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 20.8 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.6872 mL	8.4361 mL	16.8722 mL
	5 mM	0.3374 mL	1.6872 mL	3.3744 mL
	10 mM	0.1687 mL	0.8436 mL	1.6872 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.