NAMPT PROTAC B4

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Ligands
NAMPT PROTAC B4

GtoPdb Ligand ID: 12271

Synonyms: compound 5 [PMID: 36442664]

Comment: This compound is a PROTAC that targets the NAD⁺ synthesising enzyme nicotinamide phosphoribosyltransferase (NAMPT) to the ubiquitin-proteasome system for degradation [1]. Its NAMPT-binding warhead (inhibitor M049-0244 [2]) is a fluorescent ligand that allows monitoring of degradation within cells, and it uses a VHL ligand to engage the E3 ligase. Reducing intracellular NAD⁺ levels is an approach that is exploited to inhibit the expansion of rapidly proliferating cancer cells.

2D Structure

Physico-chemical Properties

Hydrogen bond acceptors	15
Hydrogen bond donors	5
Rotatable bonds	30
Topological polar surface area	245.85
Molecular weight	1051.54
XLogP	9.43
No. Lipinski's rules broken	3

SMILES / InChI / InChIKey

Canonical SMILES	CCCn1c2cc(ccc2nc(c1=O)c1ccc(cc1)C(=O)NCc1cccnc1)NC(=O)CCCCCCCCCCC(=O)N[C@@H](C(C)(C)C)C(=O)N1C[C@@H](C[C@H]1C(=O)N[C@H](c1ccc(cc1)c1scnc1C)C)O
Isomeric SMILES	O=c1n(CCC)c2c(nc1c1ccc(C(=O)NCc3cnccc3)cc1)ccc(c2)NC(=O)CCCCCCCCCCC(=O)N[C@H](C(=O)N1C[C@@H](C[C@H]1C(=O)N[C@H](c1ccc(cc1)c1c(ncs1)C)C)O)C(C)(C)C
InChI	InChI=1S/C59H73N9O7S/c1-7-31-67-48-32-45(28-29-47(48)65-52(57(67)74)42-22-26-44(27-23-42)55(72)61-35-40-17-16-30-60-34-40)64-50(70)18-14-12-10-8-9-11-13-15-19-51(71)66-54(59(4,5)6)58(75)68-36-46(69)33-49(68)56(73)63-38(2)41-20-24-43(25-21-41)53-39(3)62-37-76-53/h16-17,20-30,32,34,37-38,46,49,54,69H,7-15,18-19,31,33,35-36H2,1-6H3,(H,61,72)(H,63,73)(H,64,70)(H,66,71)/t38-,46+,49-,54+/m0/s1
InChI Key	MLJZDBCOWWJHEE-LPLKMGJNSA-N