| Chemical Properties | Back Directory | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 50 mg/mL (90.64 mM; Need ultrasonic) | [form ]
Solid | [color ]
White to off-white | [InChIKey]
DORJQZDOULKINH-VAOSCPPKNA-N | [SMILES]
C(CC(=O)O)CCC(=O)O.N(C1C=CC2=NC=C(C3C=CC(OC[C@H](N)C)=CC=3)N2N=1)[C@@H](C1C=CC=C(F)C=1)C |&1:24,31,r| |
| Hazard Information | Back Directory | [Uses]
Taletrectinib (DS-6051b) is a potent, orally active, and next-generation selective ROS1/NTRK inhibitor. Taletrectinib potently inhibits recombinant ROS1, NTRK1, NTRK2, and NTRK3 with IC50s of 0.207, 0.622, 2.28, and 0.98 nM, respectively. Taletrectinib also inhibits ROS1 G2032R and other Crizotinib-resistant ROS1 mutants[1][2]. | [in vivo]
Taletrectinib (DS-6051b) (25-200 mg/kg; p.o.; once daily for 18 days) shows antitumor activity[1].
Taletrectinib (6.25-200 mg/kg; p.o.; once daily for 8 days) inhibits NTRK-rearranged cancer in Balb-c nu/nu mice bearing KM12 cells[1].
Taletrectinib (3-100 mg/kg; p.o.; once daily for 4 days) shows rapid tumor regression in the wild-type (WT) and the G2032R-mutant Ba/F3-bearing mice without severe body weight loss[1]. | Animal Model: | Balb-c nu/nu mice (bearing U-118 MG cells)[1] | | Dosage: | 25, 50, 100, and 200?mg/kg | | Administration: | P.o.; once daily for 18 days | | Result: | Effectively inhibited tumor growth at ≥25?mg/kg without significant body weight loss.
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| [References]
[1] Katayama R, et al. The new-generation selective ROS1/NTRK inhibitor DS-6051b overcomes crizotinib resistant ROS1-G2032R mutation in preclinical models. Nat Commun. 2019;10(1):3604. Published 2019 Aug 9. DOI:10.1038/s41467-019-11496-z
[2] Fujiwara Y, et al. Safety and pharmacokinetics of DS-6051b in Japanese patients with non-small cell lung cancer harboring ROS1 fusions: a phase I study. Oncotarget. 2018;9(34):23729-23737. Published 2018 May 4. DOI:10.18632/oncotarget.25263 |
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