5.04907

Tankyrase 1/2 Inhibitor VI, G007-LK

• Synonim(y): Tankyrase 1/2 Inhibitor VI, G007-LK, TNKS1/2 Inhibitor VI, G007LK, Wnt Pathway Inhibitor XXI, 4-(5-(( E)-2-(4-(2-Chlorophenyl)-5-(5-(methylsulfonyl)pyridin-2-yl)-4H-1,2,4-triazol-3-yl)ethenyl)-1,3,4-oxadiazol-2-yl)benzonitrile, TNKS1/2 Inhibitor VI, G007LK, Wnt Pathway Inhibitor XXI, 4-(5-((E)-2-(4-(2-Chlorophenyl)-5-(5-(methylsulfonyl)pyridin-2-yl)-4H-1,2,4-triazol-3-yl)ethenyl)-1,3,4-oxadiazol-2-yl)benzonitrile
• Wzór empiryczny (zapis Hilla): C₂₅H₁₆ClN₇O₃S
• Numer CAS: 1380672-07-0
• Masa cząsteczkowa: 529.96
• Numer MDL: MFCD28167833
• Kod UNSPSC: 12352200
• NACRES: NA.77

Właściwości

• Próba: ≥98% (HPLC)
• Poziom jakości: 100
• Formularz: powder
• producent / nazwa handlowa: Calbiochem^®
• warunki przechowywania: OK to freeze; protect from light
• kolor: white
• rozpuszczalność: DMSO: 25 mg/mL
• temp. przechowywania: 2-8°C
• ciąg SMILES: [S](=O)(=O)(C)c1cnc(cc1)c2[n](c(nn2)\C=C\c4nnc([o]4)c5ccc(cc5)C#N)c3c(cccc3)Cl
• InChI: 1S/C25H16ClN7O3S/c1-37(34,35)18-10-11-20(28-15-18)24-31-29-22(33(24)21-5-3-2-4-19(21)26)12-13-23-30-32-25(36-23)17-8-6-16(14-27)7-9-17/h2-13,15H,1H3/b13-12+
• Klucz InChI: HIWVLHPKZNBSBE-OUKQBFOZSA-N

Opis

Opis ogólny

A cell-permeable, triazolyl-vinyl-oxadiazole compound that targets adenosine site of the NAD⁺ pocket in the TNKS PARP domain and acts as a potent and highly selective tankyrase inhibitor (IC₅₀ = 33 and 26 nM, respectively, against TNKS1/PARP5a/ARTD5 and TNKS2/PARP5b/ARTD6 in auto-PARsylation assays), effectively inhibiting murine Wnt3a-induced reporter activity in human HEK293 and murine 10T1/2 cultures (IC_max ~300 and 600 nM, respectively). Shown to display little or no inhibitory potency (IC₅₀ >10 µM) toward 7 other PARP enzymes (PARP1, 2, 3, 6, 7,10,11), 90 kinases, 16 phosphatases, and 75 GPCRs (IC₅₀ >10 µM). Shown to inhibit two CRC lines, COLO-320DM & SW403, colony formation in vitro (200 nM) and tumor expansion in mice in vivo (20 mg/kg via daily i.p.), although G007-LK toxicity is observed at higher dosages (≥30 mg/kg/12 h or 60 mg/kg/d via i.p.).

Please note that the molecular weight for this compound is batch-specific due to variable water content.

A cell-permeable, triazolyl-vinyl-oxadiazole compound that targets adenosine site of the NAD⁺ pocket in the TNKS PARP domain and acts as a potent and highly selective tankyrase inhibitor (IC₅₀ = 33 and 26 nM, respectively, in TNKS1/PARP5a/ARTD5 and TNKS2/PARP5b/ARTD6 auto-PARsylation assays), effectively inhibiting murine Wnt3a-induced reporter activity in human HEK293 and murine 10T1/2 cultures (IC_max ~300 and 600 nM, respectively). In addition to being more selective over PARP1/2 (IC₅₀ >10 µM vs 116 nM/47 nM with XAV939) than the nicotinamide site-targeting XAV939 (Cat. No. 575545), G007-LK is also shown to display little or no inhibitory potency (IC₅₀ >10 µM) toward 5 other PARP enzymes (PARP3, 6, 7,10,11), 90 kinases, 16 phosphatases, and 75 GPCRs (IC₅₀ >10 µM). Wnt signaling inhibition upon G007-LK treatment in 11 APC (Adenomatous polyposis coli/deleted in polyposis 2.5/DP2.5) mutatant CRC (colorectal cancer) lines ranges from no effect to varying degrees of partial blockages that do not correlate with the observed CRC colony formation inhibitions.Two CRC lines, COLO-320DM & SW403, whose colony formation are affected by G007-LK in vitro (by 70% and 27%, respectively, at 200 nM in 7 to 13 d) are also inhibited by G007-LK for their tumor expansion in mice in vivo (by 47% and 42%, respectively, on d21; 20 mg/kg per daily i.p.), while G007-LK toxicity is observed at high dosages in mice (≥30 mg/kg/12 h or 60 mg/kg/d via i.p.) due to small intestine damage as a result of on-target wnt signaling inhibition in normal tissue. Exhibits favorable pharmacokinetic properties in mice when administered via i.p. ( Plasma t_1/2 ≥2.73 h; C_max ≥2.358 µg/mL; 5 mg/kg) or p.o. ( Plasma t_1/2 ≥2.8 h; C_max ≥871 ng/mL; 5 mg/kg).

Działania biochem./fizjol.

Cell permeable: yes

Primary Target
Tankyrase 1/2

Reversible: yes

Opakowanie

Packaged under inert gas

Ostrzeżenie

Toxicity: Standard Handling (A)

Rekonstytucja

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Inne uwagi

Lau, T., et al. 2013. Cancer Res.73, 3132.
Voronkov, A., et al. 2013. J. Med. Chem.56, 3012.

Informacje prawne

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

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Informacja o środkach bezpieczeństwa

• Kod klasy składowania: 11 - Combustible Solids
• Klasa zagrożenia wodnego (WGK): WGK 2
• Temperatura zapłonu (°F): Not applicable
• Temperatura zapłonu (°C): Not applicable