(E/Z)-Zotiraciclib

Research use only, not for human use.

(E/Z)-Zotiraciclib inhibits CDK2, JAK2, and FLT3 effectively with IC50s of 13, 73, and 56 nM, respectively.

(E/Z)-Zotiraciclib inhibits CDK2, JAK2, and FLT3 effectively with IC50s of 13, 73, and 56 nM, respectively.(In Vitro):(E/Z)-Zotiraciclib has a highly novel kinase inhibitory spectrum inhibiting 17 kinases from a panel of 63, 11 of which are CDK/JAK/FLT family members. Human CYP1A2, 3A4, 2C9, and 2C19 isoforms are not inhibited by (E/Z)-Zotiraciclib at the highest tested concentration of 25 μM, but (E/Z)-Zotiraciclib inhibits CYP2D6 with an IC50 of 0.95 μM, approximately at the plasma Cmax observed at the maximum tolerated dose. (E/Z)-Zotiraciclib inhibits cell proliferation concentrations in HCT-116 with an IC50 of 0.079 μM and HL-60 with an IC50 of 0.059 μM. (E/Z)-Zotiraciclib is a novel small molecule potent CDK/JAK2/FLT3 inhibitor and mainly metabolized by CYP3A4 and CY1A2 in vitro.(In Vivo):Treatment with (E/Z)-Zotiraciclib (75 mg/kg p.o. q.d. 3×/week) significantly inhibits the growth of tumors with a mean TGI of 82%, while the lower dose(50 mg/kg p.o. 3×/week) is marginally effective. Treatment with (E/Z)-Zotiraciclib using either regime significantly inhibits the growth of tumors with mean TGIs of 42% and 63% for the oral and ip delivery methods, respectively. In pharmacokinetic studies, (E/Z)-Zotiraciclib shows moderate to high systemic clearance (relative to liver blood flow), high volume of distribution (>0.6 L/kg), the oral bioavailability of 24%, ~4 and 37% in mice, rats, and dogs, respectively; and extensive tissue distribution in mice.

(E/Z)-Zotiraciclib (0-10 μM) shows potent inhibition to CDK2, JAK2 and FLT3 with IC50s of 13, 73 and 56 nM, respectively.(E/Z)-Zotiraciclib (0-10 μM; 48 h) inhibits proliferation of cancer cells.(E/Z)-Zotiraciclib (8-1000 nM; 24 h) potently inhibits the CDK2 biomarker pRb in HCT-116 cells and potently againsts pRb in MV4-11 cells with an IC50 value of 0.13 μM. Cell Proliferation Assay Cell Line:HL-60, HCT-116, RAMOS, COLO205 and DU145 cell lines Concentration:0-10 μM Incubation Time:48 h Result:Inhibited proliferation of HL-60, HCT-116, RAMOS, COLO205 and DU145 cells with IC50s of 0.059, 0.079, 0.033, 0.072 and 0.14 μM, respectively.

(E/Z)-Zotiraciclib (50 and 75 mg/kg; p.o. once daily for 3 weeks) inhibits tumor growth.(E/Z)-Zotiraciclib (15 and 75 mg/kg; p.o. once daily 2 days on and 5 days off; i.p. once daily 5 days on 5 days off) inhibits tumor growth in two manners. Animal Model:Male BALB/c mice with HCT-116 colon cancer cells xenografts Dosage:50 and 75 mg/kg Administration:Oral gavage; 50 and 75 mg/kg once daily for 3 weeks Result:Significantly inhibited the growth of tumors with a mean TGI of 82%.Animal Model:Male BALB/c mice with lymphoma Ramos cells xenografts Dosage:15 and 75 mg/kg Administration:Oral gavage and intraperitoneal injection ; 75 mg/kg once daily 2 days on and 5 days off (p.o.) and 15 mg/kg once daily 5 days on 5 days off (i.p.)Result:Significantly inhibited the growth of tumors with mean TGIs of 42% and 63% for the oral and ip delivery methods, respectively.

(E/Z)-SB1317 | (E/Z)-TG02

Angiogenesis

FLT

COX-1|COX-2

——

——

937270-47-8

372.46

C23H24N4O

>98% (HPLC)

In Vitro:?DMSO : 26.5 mg/mL (71.15 mM)

CN(CC=CCCOc1cc(-c2nc(N3)ncc2)ccc1)Cc1cccc3c1

——

(-20℃)

With Ice Pack

≥ 2 years