Pirtobrutinib

• CAS: 2101700-15-4
• Catalog Number: ACM2101700154
• Category: Inhibitors
• Molecular Weight: 479.44
• Molecular Formula: C22H21F4N5O3
• Description: Pirtobrutinib, also known as LOXO-305 and LY 3527727, is a Bruton's tyrosine kinase (BTK) inhibitor and antineoplastic agent. Pirtobrutinib showed promising initial efficacy in pts with pretreated Richter transformation with extremely poor prognosis, including in patients who had received prior chemoimmunotherapy and covalent BTK inhibitors. Pirtobrutinib is a highly selective and potent non-covalent BTK inhibitor (BTKi) with high oral bioavailability and a long half-life, resulting in robust BTK target coverage even in high-grade malignancies with high BTK protein turnover.
• Synonyms: Pirtobrutinib; LOXO-305; LOXO 305; LOXO305; LY 3527727; LY-3527727; LY3527727
• IUPAC Name: (S)-5-amino-3-(4-((5-fluoro-2-methoxybenzamido)methyl)phenyl)-1-(1,1,1-trifluoropropan-2-yl)-1H-pyrazole-4-carboxamide
• Canonical SMILES: O=C(C1=C(N)N([C@@H](C)C(F)(F)F)N=C1C2=CC=C(CNC(C3=CC(F)=CC=C3OC)=O)C=C2)N
• InChI: InChI=1S/C22H21F4N5O3/c1-11(22(24,25)26)31-19(27)17(20(28)32)18(30-31)13-5-3-12(4-6-13)10-29-21(33)15-9-14(23)7-8-16(15)34-2/h3-9,11H,10,27H2,1-2H3,(H2,28,32)(H,29,33)/t11-/m0/s1
• InChI Key: FWZAWAUZXYCBKZ-NSHDSACASA-N
• Solubility: To be determined
• Appearance: Solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Biological Target: Pirtobrutinib (LOXO-305), a highly selective and non-covalent next generation BTK inhibitor, inhibits diverse BTK C481 substitution mutations.
• Drug Formulation: To be determined
• Elemental Analysis: C, 55.12; H, 4.42; F, 15.85; N, 14.61; O, 10.01
• Exact Mass: 479.1581
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: LOXO-305 potently inhibits Y223 autophosphorylation of all active BTK mutants (BTK C481S, C481T, and C481R). In vitro studies showed that LOXO-305 potently led to inhibition of BCR signaling and cell survival in both treatment-naive and BTK C481 mutant CLL primary cells, indicating that LOXO-305 could be used for treating treatment-naïve and ibrutinib-resistant CLL patients [60-62]. In high proliferating tumors, high rates of BTK turnover may result in incomplete target inhibition by covalent inhibitors, which ultimately lead to resistance to these covalent BTK inhibitors. LOXO-305 achieves remarkable target coverage even in the presence of high rates of BTK turnover, providing a rationale for using LOXO-305 in aggressive B cell lymphomas including DLBCL.; Reference: J Hematol Oncol. 2021; 14: 40. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937220/
• In Vivo Activity: TBD
• Shipping: 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.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).