sarm1

SARM1-IN-2 is a potent SARM1 inhibitor for the study of metabolic and neurological related diseases.

Isoquinoline, 5-iodo- is a potent and selective inhibitor of SARM1(IC50 = 75 nM) by preventing axonal degeneration and by allowing functional recovery of a metastable pool of damaged, but viable, axons.

SARM1-IN-4 (Compound 7) is an orally active SARM1 inhibitor that reduces plasma neurofilament light chain (NfL) levels in a mouse model following a 50 mg/kg oral dose. By inhibiting the NAD+ hydrolase activity of SARM1, it prevents programmed axon degeneration, making it useful for research in neurodegenerative and neurological diseases such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, and peripheral neuropathy.

SARM1-IN-5 (compound 1-23-a) is an inhibitor of SARM1, useful for researching diseases related to axonal degeneration, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS).

SARM1-IN-6 (Compound 17a) is a brain-penetrant orthosteric inhibitor of SARM1. It exhibits an IC50 of 14 nM against NAM and 74 nM against HEK cells.

SARM1-IN-7 is a potent, orally active inhibitor of SARM1, targeting its active site (orthosteric). This compound persistently enhances SARM1's enzymatic activity, leading to exacerbated NAD depletion at suboptimal concentrations. In both cell and mouse models with activated SARM1, SARM1-IN-7 exhibits dual effects: high doses provide cell/neuron protection, whereas low doses intensify cell/neuron damage. SARM1-IN-7 is applicable in studies of axonal degeneration.

SARM1-IN-8 (compound 6) is a competitive base-exchange inhibitor of SARM1. It competitively inhibits the activity of the NAD+ substrate SARM1Δ1-27.

SARM1-IN-3 (Example 30) is an inhibitor of SARM1. This compound is employed in the study of chemotherapy-induced peripheral neuropathy (CIPN).

Sulfo-ara-F-NMN is an analogue of nicotinamide mononucleotide (NMN) with cellular permeability. Sulfo-ara-F-NMN was selective to activate SARM1 and inhibited CD38 with an IC50 of about 10 μM. Activation by Sulfo-ara-F-NMN to Z-48 or NMN, which has a higher cyclase activity, causes conformational changes in SARM1, resulting in cADPR production, NAD depletion, and non-apoptotic cell death.

Acid Ceramidase-IN-3 is an inhibitor of acid ceramidase (aCDase). It shows a pIC50 of 8.5 in enzymatic assays and a pIC50 of 6.8 in A375 melanoma cell assays for aCDase enzyme activity inhibition. Acid Ceramidase-IN-3 promotes hepatic stellate cell (HSC) inactivation, measured by dose-dependent reduction of COL1A1 and ACTA2 levels. Additionally, it inhibits aCDase activity in HSCs, facilitating their inactivation and inhibiting YAP/TAZ nuclear localization. The compound enhances the expression of dynein/kinesin-related proteins (NDE1, NDEL1, KIF3B, KIF15) while reducing the expression of proteins related to various signaling pathways (SARM1, RGAP1, PDGF-D, PDGFR-B). Acid Ceramidase-IN-3 is valuable for fibrosis disease research.

GNE-5152 is a straight-chain SARM1 base exchange (BE) inhibitor. Under mild activation conditions, GNE-5152 persistently activates SARM1 at sub-inhibitory concentrations, which synergistically enhances NAD consumption, leading to axonal degeneration and neurodegeneration, and releases neurofilament light chain (NfL) in cortical neurons. GNE-5152 is applicable in neurodegenerative disease research.

NB-3 is an inhibitor of SARM1, the NAD⁺ hydrolase. NB-3 can block the hydrolysis process of NAD⁺ and form a covalent bond with the reaction product adenosine diphosphate ribose (ADPR). The small-molecule ADPR adduct formed by the binding of NB-3 and ADPR shows excellent activity and exerts neuroprotective effects in nerve injury-related scenarios.

Phenazopyridine is an orally administered azo dye with local analgesic effects on urinary tract infections, causing urine to turn orange to red. Phenazopyridine exhibits micromolar-level inhibitory activity against SARM1 and TRPM8.

5-Chloroisoquinoline (compound 42) acts as an inhibitor of SARM1 (Sterile alpha and toll/interleukin receptor (TIR) motif containing protein 1), an enzyme involved in axonal degeneration through a ternary complex mechanism mediating various activities. This compound is utilized in research related to neurodegenerative diseases or axonal degeneration.