Synonym
TPX-0005; TPX 0005; TPX0005; Ropotrectinib; REPOTRECTINIB; Repotrectinib
IUPAC/Chemical Name
(7S,13R)-11-fluoro-6,7,13,14-tetrahydro-7,13-dimethyl-1,15-etheno-1H-pyrazolo[4,3-f][1,4,8,10]benzoxatriazacyclotridecin-4(5H)-one
InChi Key
FIKPXCOQUIZNHB-WDEREUQCSA-N
InChi Code
InChI=1S/C18H18FN5O2/c1-10-8-20-18(25)14-9-21-24-6-5-16(23-17(14)24)22-11(2)13-7-12(19)3-4-15(13)26-10/h3-7,9-11H,8H2,1-2H3,(H,20,25)(H,22,23)/t10-,11+/m0/s1
SMILES Code
O=C1NC[C@H](C)OC2=CC=C(F)C=C2[C@@H](C)NC3=NC4=C1C=NN4C=C3
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Repotrectinib (TPX-0005) is a ROS1 (IC50=0.07 nM) and TRK (IC50=0.83/0.05/0.1 nM for TRKA/B/C) inhibitor.
In vitro activity:
In order to determine if repotrectinib has anti-carcinogenic activity in a neuroblastoma setting, its effects on cell proliferation were studied using two sets of neuroblastoma cell lines. Cells were treated with increasing concentrations of repotrectinib. Upon treatment with repotrectinib the proliferation rate was decreased (Fig. 1, Table 1), and the effect was more pronounced in ALK-addicted cells (almost two fold reduction in IC50 compared to ALK non-addicted cells) (Fig. 1a). Immunoblotting analysis of CLB-BAR and CLB-GE cell lysates treated with the ALK TKI confirmed that repotrectinib reduced pY1604-ALK, pERK5, pSTAT3, p-p70 S6K, pAKT and pERK levels (Fig. 1c).
Reference: Sci Rep. 2019 Dec 18;9(1):19353. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920469/
In vivo activity:
A mouse xenograft model was employed to investigate repotrectinib in neuroblastoma. Animals treated with repotrectinib displayed minor increases in tumor volume during the 14 day treatment (Fig. 4a). Tumor growth inhibition (TGI) values of 87.07% were observed with repotrectinib (Fig. 4a). Upon repotrectinib drug release after 14 days tumor growth resumed (Fig. 4a). Tumors in the vehicle control group continued to grow reaching a significant increase compared to repotrectinib treatment after day 6 (p = 0.008) (Fig. 4a). Tumor volume and weight were significantly decreased at day 14 in the repotrectinib group. In addition to effective inhibition of tumor growth, animals treated with repotrectinib exhibited an increase in weight, showing a significant weight gain over the 14 day experiment (p < 0.0001 at day 14) (Fig. 4b).
Reference: Sci Rep. 2019 Dec 18;9(1):19353. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920469/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
35.0 |
98.50 |
| Ethanol |
10.0 |
28.10 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
355.37
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Cervantes-Madrid D, Szydzik J, Lind DE, Borenäs M, Bemark M, Cui J, Palmer RH, Hallberg B. Repotrectinib (TPX-0005), effectively reduces growth of ALK driven neuroblastoma cells. Sci Rep. 2019 Dec 18;9(1):19353. doi: 10.1038/s41598-019-55060-7. PMID: 31852910; PMCID: PMC6920469.
In vitro protocol:
1. Cervantes-Madrid D, Szydzik J, Lind DE, Borenäs M, Bemark M, Cui J, Palmer RH, Hallberg B. Repotrectinib (TPX-0005), effectively reduces growth of ALK driven neuroblastoma cells. Sci Rep. 2019 Dec 18;9(1):19353. doi: 10.1038/s41598-019-55060-7. PMID: 31852910; PMCID: PMC6920469.
In vivo protocol:
1. Cervantes-Madrid D, Szydzik J, Lind DE, Borenäs M, Bemark M, Cui J, Palmer RH, Hallberg B. Repotrectinib (TPX-0005), effectively reduces growth of ALK driven neuroblastoma cells. Sci Rep. 2019 Dec 18;9(1):19353. doi: 10.1038/s41598-019-55060-7. PMID: 31852910; PMCID: PMC6920469.
1: Karachaliou N, Chaib I, Cardona AF, Berenguer J, Bracht JWP, Yang J, Cai X,
Wang Z, Hu C, Drozdowskyj A, Servat CC, Servat JC, Ito M, Attili I, Aldeguer E,
Capitan AG, Rodriguez J, Rojas L, Viteri S, Molina-Vila MA, Ou SI, Okada M, Mok
TS, Bivona TG, Ono M, Cui J, Cajal SRY, Cao P, Rosell R. Common Co-activation of
AXL and CDCP1 in EGFR-mutation-positive Non-smallcell Lung Cancer Associated With
Poor Prognosis. EBioMedicine. 2018 Feb 5. pii: S2352-3964(18)30050-1. doi:
10.1016/j.ebiom.2018.02.001. [Epub ahead of print] PubMed PMID: 29433983.
