SARM1 (Hydrolase Activity) Assay Service
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Target
SARM1 (Hydrolase Activity)
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Description
Screening and/or profiling inhibitor compounds against SARM1 hydrolase activity in a biochemical assay.
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Synonyms
Sterile Alpha And TIR Motif Containing 1, and SAMD2, NAD(+) hydrolase SARM1, HsTIR, hSARM1, MyD88-5, NADase SARM1
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Example Data
*Example only, final data may vary.
Assay Details
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Assay Format
Fluorogenic
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Reference Compounds and IC50
DSRM-3716, 15 μM
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Assay Principle
Hydrolase activity of SARM1 is measured by following the hydrolysis of Etheno-NAD to form Etheno-ADPR + nicotinamide. Etheno-NAD is not fluorescent due to internal quenching. Upon hydrolysis by SARM1, nicotinamide is released, leading to an increase in fluorescence signal directly proportional to the enzymatic activity.
Target Details
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Protein Family
Apoptosis
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UniProt
Q6SZW1
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Background
SARM1 (Sterile alpha and TIR motif containing 1) is a member of the Toll/Interleukin receptor-1 (TIR1) family of enzymes. It functions as an ADP-ribosyl cyclase and nicotinamide adenine dinucleotide (NAD) glycohydrolase. SARM1-TIR domains have intrinsic NADase activity, cleaving NAD+ into ADP Ribose (ADPR), cyclic ADPR, and Nicotinamide. Often associated with mitochondria, the protein functions as a sensor of metabolic stress. It is highly expressed in neurons, where it causes the depletion of axonal NAD+ and pathological axon loss.
SARM1 functions downstream of NMNAT2 (nicotinamide nucleotide adenylyltransferase 2) to promote the active process of injury-induced neuronal degeneration known as Wallerian degeneration. Constitutive NADase activity resulting from mutation in the human SARM1 gene has been observed in neurodegenerative disease amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease). Alternatively, loss of SARM1 activity protects neurons in models of brain injury or drug-induced neuron damage. Therefore, inhibition of SARM1 NAD+ cleavage activity may potentially reduce axonal degeneration.
Delivery
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Estimated Turnaround
Two to three weeks following delivery of compounds
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Results
Extensive report with raw and analyzed data, graphs, and detailed protocols. Includes positive control for inhibition.
