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MedKoo Cat#: 206854 | Name: Selitrectinib
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Selitrectinib, also known as LOXO-195 and BAY 2731954, is a potent and selective TRK inhibitor capable of addressing potential mechanisms of acquired resistance that may emerge in patients receiving larotrectinib (LOXO-101) or multikinase inhibitors with anti-TRK activity. LOXO-195 demonstrated potent inhibition of TRK fusions, including critical acquired resistance mutations, in enzyme and cellular assays, with minimal activity against other kinases. In diverse TRK fusion mouse models, LOXO-195 inhibited phospho-ERK and caused dramatic tumor growth inhibition, superior to first generation TRK inhibitors, without significant toxicity.

Chemical Structure

Selitrectinib
CAS#2097002-61-2

Theoretical Analysis

MedKoo Cat#: 206854

Name: Selitrectinib

CAS#: 2097002-61-2

Chemical Formula: C20H21FN6O

Exact Mass: 380.1761

Molecular Weight: 380.43

Elemental Analysis: C, 63.14; H, 5.56; F, 4.99; N, 22.09; O, 4.21

Price and Availability

Size Price Availability Quantity
5mg USD 90.00 Ready to ship
10mg USD 150.00 Ready to ship
25mg USD 250.00 Ready to ship
50mg USD 450.00 Ready to ship
100mg USD 750.00 Ready to ship
200mg USD 1,250.00 Ready to ship
500mg USD 2,650.00 Ready to ship
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Related CAS #
2097002-61-2 2097002-59-8 (RS-isomer) 1350884-56-8 (RR and RS)
Synonym
LOXO-195; LOXO 195; LOXO195; BAY 2731954; BAY-2731954; BAY2731954; Selitrectinib
IUPAC/Chemical Name
(13E,14E,22R,6R)-35-fluoro-6-methyl-7-aza-1(5,3)-pyrazolo[1,5-a]pyrimidina-3(3,2)-pyridina-2(1,2)-pyrrolidinacyclooctaphan-8-one
InChi Key
OEBIHOVSAMBXIB-SJKOYZFVSA-N
InChi Code
InChI=1S/C20H21FN6O/c1-12-4-5-16-14(9-13(21)10-22-16)17-3-2-7-26(17)18-6-8-27-19(25-18)15(11-23-27)20(28)24-12/h6,8-12,17H,2-5,7H2,1H3,(H,24,28)/t12-,17-/m1/s1
SMILES Code
FC1=CN=C(CC[C@@H](C)NC(C2=C3N(C=CC4=N3)N=C2)=O)C([C@@H]5N4CCC5)=C1
Appearance
Solid powder
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
More Info
Biological target:
Selitrectinib is a next-generation TRK kinase inhibitor, with IC50s of 0.6 nM and <2.5 nM for TRKA and TRKC, respectively.
In vitro activity:
To be determined
In vivo activity:
LOXO-195 demonstrated efficacy against various TRK fusion-positive cancers in enzyme assays, cell models, and in vivo. Two patients with acquired resistance to larotrectinib were treated with LOXO-195, which led to rapid tumor responses. Reference: Cancer Discov. 2017 Sep;7(9):963-972. https://pubmed.ncbi.nlm.nih.gov/28578312/
Solvent mg/mL mM comments
Solubility
DMSO 62.5 164.29
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 380.43 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.

Recalculate based on batch purity %
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. Drilon A, Nagasubramanian R, Blake JF, Ku N, Tuch BB, Ebata K, Smith S, Lauriault V, Kolakowski GR, Brandhuber BJ, Larsen PD, Bouhana KS, Winski SL, Hamor R, Wu WI, Parker A, Morales TH, Sullivan FX, DeWolf WE, Wollenberg LA, Gordon PR, Douglas-Lindsay DN, Scaltriti M, Benayed R, Raj S, Hanusch B, Schram AM, Jonsson P, Berger MF, Hechtman JF, Taylor BS, Andrews S, Rothenberg SM, Hyman DM. A Next-Generation TRK Kinase Inhibitor Overcomes Acquired Resistance to Prior TRK Kinase Inhibition in Patients with TRK Fusion-Positive Solid Tumors. Cancer Discov. 2017 Sep;7(9):963-972. doi: 10.1158/2159-8290.CD-17-0507. Epub 2017 Jun 3. PMID: 28578312; PMCID: PMC5581710.
In vitro protocol:
To be determined
In vivo protocol:
1. Drilon A, Nagasubramanian R, Blake JF, Ku N, Tuch BB, Ebata K, Smith S, Lauriault V, Kolakowski GR, Brandhuber BJ, Larsen PD, Bouhana KS, Winski SL, Hamor R, Wu WI, Parker A, Morales TH, Sullivan FX, DeWolf WE, Wollenberg LA, Gordon PR, Douglas-Lindsay DN, Scaltriti M, Benayed R, Raj S, Hanusch B, Schram AM, Jonsson P, Berger MF, Hechtman JF, Taylor BS, Andrews S, Rothenberg SM, Hyman DM. A Next-Generation TRK Kinase Inhibitor Overcomes Acquired Resistance to Prior TRK Kinase Inhibition in Patients with TRK Fusion-Positive Solid Tumors. Cancer Discov. 2017 Sep;7(9):963-972. doi: 10.1158/2159-8290.CD-17-0507. Epub 2017 Jun 3. PMID: 28578312; PMCID: PMC5581710.
1: Mahajan AT, Shivani, Datusalia AK, Coluccini C, Coghi P, Chaudhary S. Pyrazolo[1,5-a]pyrimidine as a Prominent Framework for Tropomyosin Receptor Kinase (Trk) Inhibitors-Synthetic Strategies and SAR Insights. Molecules. 2024 Jul 29;29(15):3560. doi: 10.3390/molecules29153560. PMID: 39124968; PMCID: PMC11314189. 2: Qin Q, Lu S, Guo Z, Li Z, Fu Q, Wang X, Wu T, Sun Y, Liu N, Zhang H, Zhao D, Cheng M. Discovery of novel indazole derivatives as second-generation TRK inhibitors. Eur J Med Chem. 2024 Oct 5;276:116640. doi: 10.1016/j.ejmech.2024.116640. Epub 2024 Jul 1. PMID: 39033612. 3: Kato Y, Matsumoto M, Takano N, Hirao M, Matsuda K, Tozuka T, Onda N, Nakamichi S, Takeuchi S, Miyanaga A, Noro R, Gemma A, Seike M. Induction of resistance to neurotrophic tropomyosin-receptor kinase inhibitors by HMGCS2 via a mevalonate pathway. Cancer Med. 2024 Jun;13(12):e7393. doi: 10.1002/cam4.7393. PMID: 38923428; PMCID: PMC11194613. 4: Roa P, Foglizzo V, Harada G, Repetto M, Kulick A, de Stanchina E, de Marchena M, Auwardt S, Sayed Ahmed S, Bremer NV, Yang SR, Feng Y, Zhou C, Kong N, Liang R, Xu H, Zhang B, Bardelli A, Toska E, Ventura A, Drilon A, Cocco E. Zurletrectinib is a next-generation TRK inhibitor with strong intracranial activity against NTRK fusion-positive tumours with on-target resistance to first-generation agents. Br J Cancer. 2024 Aug;131(3):601-610. doi: 10.1038/s41416-024-02760-1. Epub 2024 Jun 20. PMID: 38902532; PMCID: PMC11300601. 5: Lippai Z, Péterfia B, Papp G, Dezső K, Bedics G, Pápai Z, Lamers MH, Kuin RC, Szuhai K, Sápi Z. A recurrent NTRK1 tyrosine kinase domain mutation pair is characteristic in a subset of dedifferentiated liposarcomas. Eur J Cancer. 2024 May;202:114005. doi: 10.1016/j.ejca.2024.114005. Epub 2024 Mar 14. PMID: 38531265. 6: Xiang S, Lu X. Selective type II TRK inhibitors overcome xDFG mutation mediated acquired resistance to the second-generation inhibitors selitrectinib and repotrectinib. Acta Pharm Sin B. 2024 Feb;14(2):517-532. doi: 10.1016/j.apsb.2023.11.010. Epub 2023 Nov 8. PMID: 38322338; PMCID: PMC10840435. 7: Cipri S, Fabozzi F, Del Baldo G, Milano GM, Boccuto L, Carai A, Mastronuzzi A. Targeted therapy for pediatric central nervous system tumors harboring mutagenic tropomyosin receptor kinases. Front Oncol. 2023 Dec 7;13:1235794. doi: 10.3389/fonc.2023.1235794. PMID: 38144536; PMCID: PMC10748602. 8: Qin Q, Guo Z, Lu S, Wang X, Fu Q, Wu T, Sun Y, Liu N, Zhang H, Zhao D, Cheng M. Discovery of novel 3-(1H-pyrazol-4-yl)-1H-indazole derivatives as potent type II TRK inhibitors against acquired resistance. Eur J Med Chem. 2024 Jan 15;264:115953. doi: 10.1016/j.ejmech.2023.115953. Epub 2023 Nov 15. PMID: 38029466. 9: Jaworski C, Iliev P, Wängler C, Wängler B, Page B, Schirrmacher R, Bailey JJ. Type I inhibitors of tropomyosin receptor kinase (Trk): a 2020-2022 patent update. Expert Opin Ther Pat. 2023 Jul-Dec;33(7-8):503-521. doi: 10.1080/13543776.2023.2262136. Epub 2023 Nov 6. PMID: 37735897. 10: Kinnunen M, Liu X, Niemelä E, Öhman T, Gawriyski L, Salokas K, Keskitalo S, Varjosalo M. The Impact of ETV6-NTRK3 Oncogenic Gene Fusions on Molecular and Signaling Pathway Alterations. Cancers (Basel). 2023 Aug 24;15(17):4246. doi: 10.3390/cancers15174246. PMID: 37686522; PMCID: PMC10486691. 11: Xiang S, Wang J, Huang H, Wang Z, Song X, Zhou Y, Jin F, He X, Zhang ZM, Tu Z, Ding K, Zhang Z, Lu X. Switch type I to type II TRK inhibitors for combating clinical resistance induced by xDFG mutation for cancer therapy. Eur J Med Chem. 2023 Jan 5;245(Pt 1):114899. doi: 10.1016/j.ejmech.2022.114899. Epub 2022 Nov 12. PMID: 36410169. 12: Malekan M, Nezamabadi SS, Samami E, Mohebalizadeh M, Saghazadeh A, Rezaei N. BDNF and its signaling in cancer. J Cancer Res Clin Oncol. 2023 Jun;149(6):2621-2636. doi: 10.1007/s00432-022-04365-8. Epub 2022 Sep 29. PMID: 36173463. 13: Aepala MR, Peiris MN, Jiang Z, Yang W, Meyer AN, Donoghue DJ. Nefarious NTRK oncogenic fusions in pediatric sarcomas: Too many to Trk. Cytokine Growth Factor Rev. 2022 Dec;68:93-106. doi: 10.1016/j.cytogfr.2022.08.003. Epub 2022 Aug 27. PMID: 36153202. 14: Gong Y, Wu FX, Wang MS, Xu HC, Zhuo LS, Yang GF, Huang W. Discovery of 3-pyrazolyl-substituted pyrazolo[1,5-a]pyrimidine derivatives as potent TRK inhibitors to overcome clinically acquired resistance. Eur J Med Chem. 2022 Nov 5;241:114654. doi: 10.1016/j.ejmech.2022.114654. Epub 2022 Aug 5. PMID: 35961071. 15: Wang ZZ, Wang MS, Wang F, Shi XX, Huang W, Hao GF, Yang GF. Exploring the kinase-inhibitor fragment interaction space facilitates the discovery of kinase inhibitor overcoming resistance by mutations. Brief Bioinform. 2022 Jul 18;23(4):bbac203. doi: 10.1093/bib/bbac203. PMID: 35649390. 16: Mei LC, Zhuo LS, Xu HC, Huang W, Hao GF, Yang GF. Conformational adjustment overcomes multiple drug-resistance mutants of tropomyosin receptor kinase. Eur J Med Chem. 2022 Jul 5;237:114406. doi: 10.1016/j.ejmech.2022.114406. Epub 2022 Apr 25. PMID: 35486994. 17: Harada G, Drilon A. TRK inhibitor activity and resistance in TRK fusion- positive cancers in adults. Cancer Genet. 2022 Jun;264-265:33-39. doi: 10.1016/j.cancergen.2022.03.002. Epub 2022 Mar 16. PMID: 35334340; PMCID: PMC9133157. 18: Zhuo LS, Wang MS, Wu FX, Xu HC, Gong Y, Yu ZC, Tian YG, Pang C, Hao GF, Huang W, Yang GF. Discovery of Next-Generation Tropomyosin Receptor Kinase Inhibitors for Combating Multiple Resistance Associated with Protein Mutation. J Med Chem. 2021 Oct 28;64(20):15503-15514. doi: 10.1021/acs.jmedchem.1c01539. Epub 2021 Oct 20. PMID: 34668694. 19: Murray BW, Rogers E, Zhai D, Deng W, Chen X, Sprengeler PA, Zhang X, Graber A, Reich SH, Stopatschinskaja S, Solomon B, Besse B, Drilon A. Molecular Characteristics of Repotrectinib That Enable Potent Inhibition of TRK Fusion Proteins and Resistant Mutations. Mol Cancer Ther. 2021 Dec;20(12):2446-2456. doi: 10.1158/1535-7163.MCT-21-0632. Epub 2021 Oct 8. PMID: 34625502; PMCID: PMC9762329. 20: Harada G, Santini FC, Wilhelm C, Drilon A. NTRK fusions in lung cancer: From biology to therapy. Lung Cancer. 2021 Nov;161:108-113. doi: 10.1016/j.lungcan.2021.09.005. Epub 2021 Sep 16. PMID: 34563714; PMCID: PMC8530887.