IACS-15414

• CAT Number: I045336
• CAS Number: 2411321-29-2
• Molecular Formula: C20H24Cl2N4O2
• Molecular Weight: 423.34
• Purity: ≥95%
• Synonyms: 6-[(3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl]-3-(2,3-dichlorophenyl)-2-methylpyrimidin-4-one
• InChI: InChI=1S/C20H24Cl2N4O2/c1-12-19(23)20(11-28-12)6-8-25(9-7-20)16-10-17(27)26(13(2)24-16)15-5-3-4-14(21)18(15)22/h3-5,10,12,19H,6-9,11,23H2,1-2H3/t12-,19+/m0/s1
• InChIKey: WYUIJDCKOPRFJO-HXPMCKFVSA-N
• SMILES: CC1C(C2(CCN(CC2)C3=CC(=O)N(C(=N3)C)C4=C(C(=CC=C4)Cl)Cl)CO1)N

IACS‑15414 (Cat No.: I045336) is a potent, orally bioavailable small‑molecule inhibitor of the protein tyrosine phosphatase SHP2 (PTPN11), with an IC₅₀ of approximately 122 nM. It exhibits robust suppression of MAPK pathway signaling and demonstrates significant anti‑tumor efficacy in receptor tyrosine kinase (RTK)-activated and KRAS mutant xenograft models. IACS‑15414 shows favorable pharmacokinetic properties across species and minimal off‑target activity, including no detectable hERG channel liability up to ~50–100 µM. Developed by MD Anderson’s IACS division, it remains in preclinical oncology research.

Reference

[1]. Czako B, et al. Discovery of 6-[(3S,4S)-4-Amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl]-3-(2,3-dichlorophenyl)-2-methyl-3,4-dihydropyrimidin-4-one (IACS-15414), a Potent and Orally Bioavailable SHP2 Inhibitor. J Med Chem. 2021 Oct 28;64(20):15141-15169.
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