TZ9

Biological Activity

TZ9 is a novel inhibitor of Rad6 ubiquitin conjugating enzyme(E2 enzyme); inhibits MDA-MB-231 cell proliferation with IC50 of ~6 uM. IC50 value: 6 uM Target: Rad6 inhibitor The bulk of MDA-MB-231 cells treated with 10 μmol/L or more SMI #9 displayed a round morphology compared with controls and less than 5 μmol/L doses of SMI #9. Simultaneous comparison of SMIs #8 and 9 confirmed SMI #9 inhibits Matrigel-induced migration of MDA-MB-231 cells in a dose-dependent manner compared with SMI #8. 5 μmol/L SMI #9 treatment triggered morphologic changes consistent with apoptosis in a time-dependent manner. 5 μmol/L SMI #9 treatment of MDA-MB-231 cells for 24 hours increased the proportion of G2–M-arrested cells by 2-fold and was accompanied by a proportional decrease in S-phase cells. SMIs #8 or 9 treatments dramatically reduced β-catenin staining as visualized by reduced merged Rad6/β-catenin yellow fluorescence.

Chemical Information

Molecular Weight	366.33
CAS Number	1002789-86-7
Solubility (25°C)	DMSO ≥ 40 mg/mL
Storage	Powder          -20°C   3 years ;  4°C   2 years In solvent       -80°C   6 months ;  -20°C   1 month

Conversion of different model animals based on BSA (PMID: 27057123)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Wei-Lun Huang, et al. High Expression of UBE2B as a Poor Prognosis Factor in Patients With Rectal Cancer Following Chemoradiotherapy

[2] Susheel Kumar Nethi, et al. Design, synthesis and characterization of doped-titanium oxide nanomaterials with environmental and angiogenic applications

[3] Hend Kothayer, et al. Synthesis and in vitro anticancer evaluation of some 4,6-diamino-1,3,5-triazine-2-carbohydrazides as Rad6 ubiquitin conjugating enzyme inhibitors

[4] Hend Kothayer, et al. Design, synthesis and in vitro anticancer evaluation of 4,6-diamino-1,3,5-triazine-2-carbohydrazides and -carboxamides