NAMPT inhibitor-linker 2

• CAT Number: I019472
• CAS Number: 2241014-82-2
• Molecular Formula: C34H33FN6O5
• Molecular Weight: 624.66
• Purity: ≥95%
• Synonyms: 4-[4-[3-(2,5-dioxopyrrol-1-yl)propanoyl]piperazin-1-yl]-N-[[2-fluoro-4-[[(1S,2S)-2-pyridin-3-ylcyclopropanecarbonyl]amino]phenyl]methyl]benzamide
• InChI: InChI=1S/C34H33FN6O5/c35-29-18-25(38-34(46)28-19-27(28)23-2-1-12-36-20-23)6-3-24(29)21-37-33(45)22-4-7-26(8-5-22)39-14-16-40(17-15-39)30(42)11-13-41-31(43)9-10-32(41)44/h1-10,12,18,20,27-28H,11,13-17,19,21H2,(H,37,45)(H,38,46)/t27-,28+/m1/s1
• InChIKey: BCYXMGSOTBLGDN-IZLXSDGUSA-N
• SMILES: C1CN(CCN1C2=CC=C(C=C2)C(=O)NCC3=C(C=C(C=C3)NC(=O)C4CC4C5=CN=CC=C5)F)C(=O)CCN6C(=O)C=CC6=O

NAMPT inhibitor-linker 2 is a agent-linker conjugates for ADC, composed of an NAMPT inhibitor as a payload, and a linker. ADC-4 consists of an NAMPT inhibitor-linker 2 and an anti-c-Kit monoclonal antibody, exihibits potent activity against c-Kit expressing cell lines such as GIST-T1 and NCI-H526, with IC50s of <7 pM and 40 pM, respectively.
ADC-4 exihibits potent activity against c-Kit expressing cell lines such as GIST-T1 and NCI-H526, with IC50s of <7 pM and 40 pM, respectively[1]. ADC-4 (0.01 nM-10 nM, 144 hours) inhibits cell proliferation of GIST-T1 cells, but does not affect the cell cycle[1].
ADC-4 (20 mg/kg, i.v. for 28 days) is tolerated, and causes tumor stasis in mice bearing GIST-T1 cells[1].

Reference

[1]. Karpov AS, et al. Nicotinamide Phosphoribosyltransferase Inhibitor as a Novel Payload for Antibody-Drug Conjugates. ACS Med Chem Lett. 2018 Jun 28;9(8):838-842.
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