Pirtobrutinib
new
featured

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

MedKoo CAT#: 465403

CAS#: 2101700-15-4

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.


Chemical Structure

img
Pirtobrutinib
CAS# 2101700-15-4

Theoretical Analysis

MedKoo Cat#: 465403
Name: Pirtobrutinib
CAS#: 2101700-15-4
Chemical Formula: C22H21F4N5O3
Exact Mass: 479.1581
Molecular Weight: 479.4356
Elemental Analysis: C, 55.12; H, 4.42; F, 15.85; N, 14.61; O, 10.01

Price and Availability

Size Price Availability Quantity
5.0mg USD 90.0 Ready to ship
10.0mg USD 165.0 Ready to ship
25.0mg USD 350.0 Ready to ship
50.0mg USD 550.0 Ready to ship
100.0mg USD 950.0 Ready to ship
200.0mg USD 1650.0 Ready to ship
Bulk inquiry

Synonym: Pirtobrutinib; LOXO-305; LOXO 305; LOXO305; LY 3527727; LY-3527727; LY3527727;

IUPAC/Chemical Name: (S)-5-amino-3-(4-((5-fluoro-2-methoxybenzamido)methyl)phenyl)-1-(1,1,1-trifluoropropan-2-yl)-1H-pyrazole-4-carboxamide

InChi Key: FWZAWAUZXYCBKZ-NSHDSACASA-N

InChi Code: 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

SMILES Code: 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

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: 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

Biological target: Pirtobrutinib (LOXO-305), a highly selective and non-covalent next generation BTK inhibitor, inhibits diverse BTK C481 substitution mutations.
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

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 50.0 104.29

Preparing Stock Solutions

The following data is based on the product molecular weight 479.4356 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. Gu D, Tang H, Wu J, Li J, Miao Y. Targeting Bruton tyrosine kinase using non-covalent inhibitors in B cell malignancies. J Hematol Oncol. 2021 Mar 6;14(1):40. doi: 10.1186/s13045-021-01049-7. PMID: 33676527; PMCID: PMC7937220.
In vitro protocol: 1. Gu D, Tang H, Wu J, Li J, Miao Y. Targeting Bruton tyrosine kinase using non-covalent inhibitors in B cell malignancies. J Hematol Oncol. 2021 Mar 6;14(1):40. doi: 10.1186/s13045-021-01049-7. PMID: 33676527; PMCID: PMC7937220.
In vivo protocol: TBD

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

1: Sarosiek S, Treon SP, Castillo JJ. How to Sequence Therapies in Waldenström Macroglobulinemia. Curr Treat Options Oncol. 2021 Aug 23;22(10):92. doi: 10.1007/s11864-021-00890-9. PMID: 34426943.

2: BTK Inhibitor May Treat Drug-Resistant CLL, SLL. Cancer Discov. 2021 May;11(5):998. doi: 10.1158/2159-8290.CD-NB2021-0327. Epub 2021 Mar 26. PMID: 33771769.

3: Romero D. Initial pirtobrutinib data show promise. Nat Rev Clin Oncol. 2021 May;18(5):258. doi: 10.1038/s41571-021-00505-0. PMID: 33758377.

4: Mato AR, Shah NN, Jurczak W, Cheah CY, Pagel JM, Woyach JA, Fakhri B, Eyre TA, Lamanna N, Patel MR, Alencar A, Lech-Maranda E, Wierda WG, Coombs CC, Gerson JN, Ghia P, Le Gouill S, Lewis DJ, Sundaram S, Cohen JB, Flinn IW, Tam CS, Barve MA, Kuss B, Taylor J, Abdel-Wahab O, Schuster SJ, Palomba ML, Lewis KL, Roeker LE, Davids MS, Tan XN, Fenske TS, Wallin J, Tsai DE, Ku NC, Zhu E, Chen J, Yin M, Nair B, Ebata K, Marella N, Brown JR, Wang M. Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1/2 study. Lancet. 2021 Mar 6;397(10277):892-901. doi: 10.1016/S0140-6736(21)00224-5. PMID: 33676628.

5: Michot JM, Ribrag V. Pirtobrutinib shows evidence to inaugurate a third generation of BTK inhibitors. Lancet. 2021 Mar 6;397(10277):855-857. doi: 10.1016/S0140-6736(21)00235-X. PMID: 33676615.



Additional Information

Pirtobrutinib is a highly potent and selective non-covalent BTK inhibitor currently being tested in B-cell malignancies. It comprises nanomolar potency against wild-type and C481-mutant BTK in cell and enzyme assays, with greater than 300-fold selectivity for BTK vs 370 other kinases. Because of reversible binding mode, BTK inhibition is not impacted by an intrinsic rate of BTK turnover, and its favorable pharmacologic properties allow for sustained BTK inhibition throughout the dosing interval.