WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 208411
CAS#: 2359649-81-1 (RSS-isomer)
Description: Enbezotinib, also known as TPX-0046, is a novel and potent RET/SRC inhibitor for RET-driven cancers. In enzymatic assays, TPX-0046 demonstrated low nanomolar potency against WT and many mutated RETs, as well as SRC, and is VEGFR2-sparing. TPX-0046 potently inhibited RET phosphorylation and cell proliferation in in-house engineered Ba/F3 KIF5B-RET, TT, and LC2/ad cells with IC50s of approximately 1 nM. TPX-0046 is potent against the SFM G810R in Ba/F3 cell proliferation assay with a mean IC50 of 17 nM, whereas comparable proxy molecules for BLU-667 and LOXO-292 have IC50s >500 nM. TPX-0046 demonstrated marked anti-tumor efficacy in vivo in multiple RET-driven cancer cell-derived and patient-derived xenograft tumor models.
MedKoo Cat#: 208411
Name: Enbezotinib
CAS#: 2359649-81-1 (RSS-isomer)
Chemical Formula: C21H21FN6O3
Exact Mass: 424.1659
Molecular Weight: 424.44
Elemental Analysis: C, 59.43; H, 4.99; F, 4.48; N, 19.80; O, 11.31
Related CAS #: 2359650-19-2 (SRR-isomer) 2359649-81-1 (RSS-isomer) Enbezotinib HCl
Synonym: TPX-0046; TPX 0046; TPX0046; Enbezotinib;
IUPAC/Chemical Name: (13E,14E,15aR,18aS,5S)-35-Fluoro-5-methyl-15,15a,16,17,18,18a-hexahydro-4-oxa-7-aza-1(5,3)-cyclopenta[b]pyrazolo[1',5':1,2]pyrimido[4,5-e][1,4]oxazina-3(3,2)-pyridinacyclooctaphan-8-one
InChi Key: BYYQDEOVMILBQT-XZJROXQQSA-N
InChi Code: InChI=1S/C21H21FN6O3/c1-11-6-23-20(29)14-8-25-28-10-17-19(26-18(14)28)27(15-3-2-4-16(15)31-17)9-12-5-13(22)7-24-21(12)30-11/h5,7-8,10-11,15-16H,2-4,6,9H2,1H3,(H,23,29)/t11-,15+,16-/m0/s1
SMILES Code: FC1=CC(CN2[C@H](CCC3)[C@H]3OC(C2=N4)=CN5C4=C6C=N5)=C(O[C@@H](C)CNC6=O)N=C1
Appearance: To be determined
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: To be determined
Shelf Life: >2 years if stored properly
Drug Formulation: To be determined
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
The following data is based on the product molecular weight 424.44 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 |
Repetto M, Crimini E, Ascione L, Boscolo Bielo L, Belli C, Curigliano G. The return of RET GateKeeper mutations? an in-silico exploratory analysis of potential resistance mechanisms to novel RET macrocyclic inhibitor TPX-0046. Invest New Drugs. 2022 Oct;40(5):1133-1136. doi: 10.1007/s10637-022-01259-x. Epub 2022 May 25. PMID: 35612671.
