NAMPT inhibitor-linker 2

NAMPT inhibitor-linker 2 is a drug-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.

Research Areas >> Cancer

Signaling Pathways >> Antibody-drug Conjugate >> Drug-Linker Conjugates for ADC

Signaling Pathways >> Metabolic Enzyme/Protease >> Nampt

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]. Cell Proliferation Assay[1] Cell Line: GIST-T1 cells Concentration: 0.1 pM-10 nM Incubation Time: 144 hours Result: Inhibited the cell proliferation of GIST-T1 cells at 0.01-10 nM, and the inhibition remained unchanged after 1 nM.

ADC-4 (20 mg/kg, i.v. for 28 days) is tolerated, and causes tumor stasis in mice bearing GIST-T1 cells[1]. Animal Model: Female scid-beige (SCID bg) mice[1] Dosage: 20 mg/kg Administration: A single intravenous injection (i.v.) for 28 days Result: Significantly inhibited the growth of tumor in mice.

[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.