JH-VIII-157-02

Research use only, not for human use.

JH-VIII-157-02 is a potent, orally active, CNS-permeable, second-generation inhibitor of ALK G1202R mutant with IC50 of 2 nM.

JH-VIII-157-02 is a potent, orally active, CNS-permeable, second-generation inhibitor of ALK G1202R mutant with IC50 of 2 nM, also shows high potency against a variety of other frequently observed mutants (G1269A, S1206Y, F1174L and C1156Y); inhibits EML4-ALKWT with IC50 of 2 nM, demonstrates inhibition of CSNK2A1 <10 uM, IRAK1 (IC50 =14 nM), IRAK4 with (IC50=465 nM), CLK4 (IC50=14 nM), RET (IC50=3 nM), RET V804L (IC50=13 nM); potently inhibits proliferation of NSCLC H3122 cell line with IC50 of 5 nM.

JH-VIII-157-02 is a structural analogue of alectinib, acts as an ALK inhibitor, and shows an IC50 of 2 nM for echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK) G1202R in cells. JH-VIII-157-02 also potently inhibits EML4-ALKwt (Eawt), EAC1156Y, EAF1174L, EAS1206Y (IC50, 2 nM), EAG1269A (IC50, 3 nM), EAL1196M (IC50, 58 nM), EA1151Tins (IC50, 107 nM), and EAL1152R (IC50, 196 nM). Moreover, JH-VIII-157-02 has selectivity at other kinases, including IRAK1, CLK4, RET, RET V804L, RET V804M and IRAK 4, and the IC50s are 14 nM, 14 nM, 3 nM, 13 nM, 12 nM, and 465 nM respectively. JH-VIII-157-02 exhibits inhibitory growth of cancer cell lines, such as H3122, DFCI76 (L1152R] with EC50s of 5, 19 nM, respectively.

JH-VIII-157-02 exhibits good oral bioavailability following an oral dose of 10 mg/kg in mice. JH-VIII-157-02 also penetrates the CNS of mice.

JH-VIII-157-02 | JH-VIII-15702 | JH-VIII-157 02 | JHVIII-157-02

Angiogenesis

ALK

ALK

Cancer

——

1639422-97-1

465.557

C28H27N5O2

>98% (HPLC)

DMSO : ≥ 25 mg/mL 53.70 mM

O=C(N(C)C)CN1N=CC(C2=C(CC)C=C3C(C(C)(C)C(NC4=C5C=CC(C#N)=C4)=C5C3=O)=C2)=C1

2-(4-(3-cyano-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-1H-pyrazol-1-yl)-N,N-dimethylacetamide

(-20℃)

With Ice Pack

≥ 2 years