Vulolisib

• CAT Number: I043357
• CAS Number: 2390105-79-8
• Molecular Formula: C18H19F2N5O3S
• Molecular Weight: 423.44
• Purity: ≥95%
• Synonyms: (2S)-2-[[2-[(4R)-4-(difluoromethyl)-2-oxo-1,3-thiazolidin-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]amino]propanamide
• InChI: InChI=1S/C18H19F2N5O3S/c1-9(16(21)26)22-10-2-3-11-13(6-10)28-5-4-24-7-14(23-17(11)24)25-12(15(19)20)8-29-18(25)27/h2-3,6-7,9,12,15,22H,4-5,8H2,1H3,(H2,21,26)/t9-,12-/m0/s1
• InChIKey: KEEKMOIRJUWKNK-CABZTGNLSA-N
• SMILES: CC(C(=O)N)NC1=CC2=C(C=C1)C3=NC(=CN3CCO2)N4C(CSC4=O)C(F)F

Vulolisib is a potent and orally active phosphatidylinositol 3-kinase (PI3K) inhibitor, with IC50 values of 0.2 nM, 168 nM, 90 nM and 49 nM for PI3Kα, PI3Kβ, PI3Kγ and PI3Kδ, respectively. Antiproliferative and antineoplastic activity[1].
Vulolisib has antiproliferative activity against PI3Kα-mutant cell lines HCC1954 (H1047R), HGC-27 (E542K) and MKN1 (E545K) with IC50s of 21 nM, 60 nM and 40 nM, respectively[1].
Vulolisib (10, 30 and 60 mg/kg; IG; daily for 7days) exhibits better tolerance and exposure than Inavolisib[1].
Vulolisib (10mg/kg; PO; daily for 19 days) inhibits tumor growth with TGI of 132%[1].
Vulolisib (5 mg/kg; IG, single dosage) exhibits favorable pharmacokinetic property[1].
Pharmacokinetic Parameters of Vulolisib in male Balb/c mice[1].

IG (5 mg/kg)

tmax (h)
0.5

Cmax (ng/mL)
1057

AUC0-t (ng/mL·h)
2185

AUC0-∞ (ng/mL·h)
2274

t1/2 (h)
1.6

MRT (h)
2.2

Reference

[1]. Xiaolan ZHAN, et al. Three fused ring derivative-containing salt or crystal form and pharmaceutical composition thereof. WO2021104146A1 (example 22)