| Stereochemistry | ABSOLUTE |
| Molecular Formula | C22H21F4N5O3 |
| Molecular Weight | 479.4275 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC=C(F)C=C1C(=O)NCC2=CC=C(C=C2)C3=NN([C@@H](C)C(F)(F)F)C(N)=C3C(N)=O
InChI
InChIKey=FWZAWAUZXYCBKZ-NSHDSACASA-N
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
| Molecular Formula | C22H21F4N5O3 |
| Molecular Weight | 479.4275 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
Pirtobrutinib is a small molecule, noncovalent inhibitor of BTK. BTK is a signaling protein of the B-cell antigen receptor (BCR) and cytokine receptor pathways. In B-cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion. Pirtobrutinib binds to wild type BTK and BTK harboring C481 mutations, leading to inhibition of BTK kinase activity. In nonclinical studies, pirtobrutinib inhibited BTK-mediated B-cell CD69 expression and inhibited malignant B-cell proliferation. Pirtobrutinib showed dose-dependent anti-tumor activities in BTK wild type and BTK C481S mutant mouse xenograft models. On January 27, 2023, the Food and Drug Administration (FDA) granted accelerated approval to pirtobrutinib (Jaypirca, Eli Lilly and Company) for relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor.
Approval Year
Doses
AEs
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
Drug as perpetrator
Drug as victim
Tox targets
PubMed
Patents
Sample Use Guides
Recommended dosage: 200 mg orally once daily; swallow whole with water, with or without food. Do not cut, crush, or chew tablets.
Route of Administration:
Oral
One-hour incubation of pirtobrutinib decreased phospho-BTK (Y223) and downstream phospho-ERK (T202/Y204) levels in all cell lines starting at 0.01 uM in BTKWT and BTKC481R and at 0.1 uM in BTKC481S cells. Treatment with pirtobrutinib also decreased phospho-PLCγ2 (Y1217) levels at 0.01 uM in BTKWT and at 0.1 uM in BTKC481S.R Y223 autophosphorylation with IC50s of 8.45, 7.23, and 11.73 nM, respectively.
