详情描述
Telomestatin is a very potent telomerase inhibitor and can be isolated from Streptomyces anulatus 3533-SV4. Telomestatin selectively facilitates the formation of intramolecular G-quadruplexes, in particular, that produced from the human telomeric sequence d[T2AG3]4. Telomestatin is an ADC cytotoxin and can be used for cancer research.
Product information
CAS Number: 265114-54-3
Molecular Weight: 582.50
Formula: C26H14N8O7S
Chemical Name: (1R)-4, 8-dimethyl-3, 7, 11, 15, 19, 23, 27-heptaoxa-31-thia-33, 34, 35, 36, 37, 38, 39, 40-octaazanonacyclo[28.2.1.1, .1, .1, .1, .1, .1, .1, ]tetraconta-2(40), 4, 6(39), 8, 10(38), 12, 14(37), 16, 18(36), 20, 22(35), 24, 26(34), 28, 30(33)-pentadecaene
Smiles: CC1OC2=NC=1C1=NC(C3=NC(=CO3)C3=NC(=CO3)C3=NC(=CO3)C3=NC(=CO3)C3=NC(=CO3)C3=N[C@H]2CS3)=C(C)O1
InChiKey: YVSQVYZBDXIXCC-INIZCTEOSA-N
InChi: InChI=1S/C26H14N8O7S/c1-9-17-24-30-14(6-39-24)21-28-12(4-37-21)19-27-11(3-35-19)20-29-13(5-36-20)22-31-15(7-38-22)26-32-16(8-42-26)23-33-18(10(2)40-23)25(34-17)41-9/h3-7,16H,8H2,1-2H3/t16-/m0/s1
Technical Data
Appearance: Solid Power
Purity: ≥98% (or refer to the Certificate of Analysis)
Solubility: Soluble in DMSO
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis
Storage Condition: Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.
Shelf Life: ≥12 months if stored properly.
Stock Solution Storage: 0 - 4 oC for 1 month or refer to the Certificate of Analysis.
Drug Formulation: To be determined
HS Tariff Code: 382200
How to use
In Vitro:
Telomestatin (0-50 μM) promotes or stabilizes the formation of the intramolecular G-quadruplex. At the DNA concentrations of 0.005 and 0.2 µM, EC50 values of 0.03 µM and 0.53 µM telomestatin are found. In a parallel experiment with the mutated oligonucleotide d[T2AGAG]4, there is no conversion of the mutated sequence to a G-quadruplex structure by telomestatin. Telomestatin (2-10 μM) effects the expression of DN-hTERT on telomerase activity and telomere length, at 10 μM，the expression of DN-hTERT shows a significant reduction of telomerase activity. Additionally, at 2 μM , the terminal restriction fragment (TRF) length of U937 cells shortens progressively from 9.5 to 3.8 kb at population doubling (PD) 20 in U937 cells. Telomestatin (2-5 μM; short-time or long trem) has less effect on normal diploid human fibroblasts and ALT-positive cells. Telomestatin (5 μM; short-time 3 days) exposure has no affect the viability of normal human fibroblasts BJ or IMR-90; however, 5 μM of telomestatin reduces the viability of GM847 cells. Telomestatin (2 μM; long-term 10-50 days) does not significantly change the proliferation rate or viability to that of control cells in BJ or IMR-90 cells and also does not change the proliferation of GM847 cells.
In Vivo:
Telomestatin (intraperitoneal injection; 3-15 mg/kg; two times a week; 4 weeks) decreases tumor telomerase activity and inhibits the growth of U937 xenografts. Systemic administrations of 3 mg/kg or 9 mg/kg or 15 mg/kg of telomestatin decreases tumor telomerase activity by 60.2%, 74% and 92.5% compared to control, respectively.
References:
- Mu-Yong Kim, et al. Telomestatin, a potent telomerase inhibitor that interacts quite specifically with the human telomeric intramolecular g-quadruplex. J Am Chem Soc. 2002 Mar 13;124(10):2098-9.
- Keita Amagai, et al. Identification of a gene cluster for telomestatin biosynthesis and heterologous expression using a specific promoter in a clean host. Sci Rep. 2017 Jun 13;7(1):3382.
- T Tauchi, et al. Telomerase inhibition with a novel G-quadruplex-interactive agent, telomestatin: in vitro and in vivo studies in acute leukemia. Oncogene. 2006 Sep 21;25(42):5719-25.
Products are for research use only. Not for human use.