Repotrectinib (TPX-0005)

製品コードS8583 バッチS858304

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C18H18FN5O2
分子量 355.37 CAS No. 1802220-02-5
Solubility (25°C)* 体外 DMSO 71 mg/mL (199.79 mM)
Ethanol 15 mg/mL (42.2 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Repotrectinib (TPX-0005) is a novel ALK/ROS1/TRK inhibitor with the IC50 values of 1.01 nM for WT ALK, 1.26 nM for ALK(G1202R), and 1.08 nM for ALK(L1196M); also a potent SRC inhibitor (IC50 5.3 nM).
in vitro TPX-0005 is an orally available and potent ATP-competitive inhibitor against ALK, ROS1, TRKA, TRKB and TRKC recombinant kinases and their corresponding clinical resistant mutants. TPX-0005 demonstrates potent anti-proliferative activity in the range of sub-nanomolar to low nanomolar in a number of human cancer cell lines and engineered stable cell lines expressing the targeted oncogenes or their solvent front mutants, accompanied by inhibition of target phosphorylation and concomitant inactivation of downstream effectors such as ERK, AKT and STAT3[2]. TPX-0005 inhibits H2228 cell migration in a wound healing assay with similar activity to saracatinib. TPX-0005 is able to not only inhibit the wild-type and a broad spectrum of mutant ALKs, but also overcome primary resistance and suppress metastatic features by inhibiting SRC[1].
in vivo In patient derived xenograft tumor models, TPX-0005 treatment results in significant regression of tumors harboring the oncogenic ALK, ROS1 and TRKC fusions. Moreover, in a series of mouse xenograft tumor models, TPX-0005 exhibits marked anti-tumor activity not only in tumors harboring the wildtype oncogenic targets but also in tumors harboring the oncogenes with the solvent front mutations via inhibition of the target phosphorylation[2].

プロトコル(参考用のみ)

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

NVL-520 Is a Selective, TRK-Sparing, and Brain-Penetrant Inhibitor of ROS1 Fusions and Secondary Resistance Mutations [ Cancer Discov, 2023, 13(3):598-615] PubMed: 36511802
Discovery of oncogenic ROS1 missense mutations with sensitivity to tyrosine kinase inhibitors [ EMBO Mol Med, 2023, 10.15252/emmm.202217367] PubMed: 37587872
CIC-mediated modulation of MAPK signaling opposes receptor tyrosine kinase inhibitor response in kinase-addicted sarcoma [ Cancer Res, 2022, canres.1397.2021] PubMed: 35074756
Inhibition of EGFR and MEK surmounts entrectinib resistance in a brain metastasis model of NTRK1-rearranged tumor cells [ Cancer Sci, 2022, 113(7):2323-2335] PubMed: 35363931
Inhibition of EGFR and MEK surmounts entrectinib resistance in a brain metastasis model of NTRK1-rearranged tumor cells [ Cancer Sci, 2022, 113(7):2323-2335] PubMed: 35363931
JND4135, a New Type II TRK Inhibitor, Overcomes TRK xDFG and Other Mutation Resistance In Vitro and In Vivo [ Molecules, 2022, 27(19)6500] PubMed: 36235036
The CLIP1-LTK fusion is an oncogenic driver in non-small-cell lung cancer [ Nature, 2021, 600(7888):319-323] PubMed: 34819663
TRK xDFG mutations trigger a sensitivity switch from type I to II kinase inhibitors [ Cancer Discov, 2020, CD-20-0571] PubMed: 33004339
Therapeutic potential of NTRK3 inhibition in desmoplastic small round cell tumor [ Clin Cancer Res, 2020, clincanres.2585.2020] PubMed: 33229458
Therapeutic potential of NTRK3 inhibition in desmoplastic small round cell tumor [ Clin Cancer Res, 2020, clincanres.2585.2020] PubMed: 33229458

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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