Mubritinib

Research use only, not for human use.

Mubritinib (TAK-165) is a potent inhibitor of HER2/ErbB2 with IC50 of 6 nM.

Mubritinib, also known as TAK-165, is a protein kinase inhibitor which was under development by Takeda for the treatment of cancer. It completed phase I clinical trials (may be discontinued since 2008). Mubritinib(TAK 165) is a potent EGFR, HER2 and p34cdc2 inhibitor with IC50 of 6 nM and 0.2 ?μM, respectively. Mubritinib(TAK 165) also inhibits p33cdk2 and p33cdk5. Mubritinib(TAK 165) displays > 4000-fold selectivity over EGFR, FGFR, PDGFR, JAK1 and Src. Mubritinib(TAK 165) exhibits potent antiproliferative effects in ErbB2-overexpressing cancer cell lines (IC50 = 5 nM in BT474 breast cancer cells) and significantly inhibits bladder, breast and prostate cancer xenograft growth in vivo. (In Vitro):Mubritinib (TAK-165) specifically inhibits HER2 tyrosine kinase with an IC50 6 nM and does not inhibit other types tyrosine kinase up to 25 000 nM. Mubritinib inhibits HER2 phosphorylation and its down-stream Akt and MAPK in HER2 strongly expressing cells (BT474 breast cancer cell line). Mubritinib sensitivity depends on HER2 levels of each cell line. Especially, BT474 cells which over-express HER2 strongly is highly sensitive (IC50=0.005 μM) and PC-3 cells which express HER2 very weakly is less sensitive (IC50=4.62 μM). But, HT1376 and ACHN cells that over-expressed EGFR showed high IC50 (IC50>25 μM).(In Vivo):In the xenograft model, treatment with Mubritinib (TAK-165) significantly inhibits growth of UMUC-3, ACHN, and LN-REC4. The antitumor effect after 14 days treatment are 22.9%, 26.0%, and 26.5% in UMUC3, ACHN and LN-REC4, respectively.

Mubritinib (TAK-165) specifically inhibits HER2 tyrosine kinase with an IC50 6 nM and does not inhibit other types tyrosine kinase up to 25 000 nM. Mubritinib inhibits HER2 phosphorylation and its down-stream Akt and MAPK in HER2 strongly expressing cells (BT474 breast cancer cell line). Mubritinib sensitivity depends on HER2 levels of each cell line. Especially, BT474 cells which over-express HER2 strongly is highly sensitive (IC50=0.005 μM) and PC-3 cells which express HER2 very weakly is less sensitive (IC50=4.62 μM). But, HT1376 and ACHN cells that over-expressed EGFR showed high IC50 (IC50>25 μM).

In the xenograft model, treatment with Mubritinib (TAK-165) significantly inhibits growth of UMUC-3, ACHN, and LN-REC4. The antitumor effect after 14 days treatment are 22.9%, 26.0%, and 26.5% in UMUC3, ACHN and LN-REC4, respectively.

Mubritinib | TAK 165 | TAK-165

Membrane Transporter/Ion Channel

TRP/TRPV Channel

EGFR| HER2/ErbB2| FGFR| JAK1| PDGFR

Cancer

——

366017-09-6

468.47

C25H23F3N4O2

>98% (HPLC)

DMSO : 50 mg/mL 106.73 mM; H2O : < 0.1 mg/mL

c1cc(ccc1CCCCn1ccnn1)OCc1coc(n1)/C=C/c1ccc(cc1)C(F)(F)F

(E)-4-((4-(4-(1H-1,2,3-triazol-1-yl)butyl)phenoxy)methyl)-2-(4-(trifluoromethyl)styryl)oxazole

(-20℃)

With Ice Pack

≥ 2 years