Pirtobrutinib Chemical Properties

Boiling point:

619.2±55.0 °C(Predicted)

Density 

1.44±0.1 g/cm3(Predicted)

storage temp. 

4°C, stored under nitrogen

solubility 

DMSO : 50 mg/mL (104.29 mM; Need ultrasonic)

form 

A solid

pka

13.32±0.46(Predicted)

color 

White to yellow

InChIKey

FWZAWAUZXYCBKZ-NSHDSACASA-N

SMILES

N1([C@@H](C)C(F)(F)F)C(N)=C(C(N)=O)C(C2=CC=C(CNC(=O)C3=CC(F)=CC=C3OC)C=C2)=N1

Pirtobrutinib Usage And Synthesis

Description

Pirtobrutinib, or 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.

Uses

Pirtobrutinib (LOXO-305), a highly selective and non-covalent next generation BTK inhibitor, inhibits diverse BTK C481 substitution mutations. Pirtobrutinib causes regression of BTK-dependent lymphoma tumors in mouse xenograft models. Pirtobrutinib is also more than 300-fold selective for BTK versus 370 other kinases tested and shows no significant inhibition of non-kinase off-targets at 1 μM[1].

References

[1] Gomez E B , et al. Loxo-305, a Highly Selective and Non-Covalent Next Generation BTK Inhibitor, Inhibits Diverse BTK C481 Substitution Mutations[J]. Blood, 2019, 134(Supplement_1):4644-4644.