SMDC818909 

SMDC818909 is an indole amide-derived uncompetitive inhibitor targeting p97 AAA+ ATPase, with an IC₅₀ of 3.5 μM and a K_a of 9.1 μM. SMDC818909 binds to the D2 ATPase domain of p97, preferentially associates with the ADP-bound conformation of p97, allosterically blocks the ATP hydrolysis cycle of p97, and inhibits its mediated intracellular protein homeostasis regulatory function. SMDC818909 is applied to the research and development of p97-targeted antitumor drugs, as well as studies on cancer-related proteotoxic stress mechanisms^[1][2][3].

SMDC818909 binds to the D2 domain of full-length p97 with a K_d of 9.1 μM^[1].
SMDC818909 (5-100 μM ATP) acts as a non-competitive inhibitor of p97 ATPase, with IC₅₀ values of 26 μM, 11.5 μM and 4.9 μM under the conditions of 5, 20 and 100 μM ATP, respectively^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

267.29

C₁₄H₁₃N₅O

1147823-21-9

O=C(NC1=CC2=C(C=C1)NC(C)=C2)C3=NC=CN=C3N

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Alverez C, et al. Allosteric Indole Amide Inhibitors of p97: Identification of a Novel Probe of the Ubiquitin Pathway. ACS Med Chem Lett. 2015;7(2):182-187. Published 2015 Dec 22.  [Content Brief]

  [2]. Bulfer S L, Arkin M R. Applying Biophysical and Biochemical Methods to the Discovery of Allosteric Modulators of the AAA ATPase p97[J]. Applied Biophysics for Drug Discovery, 2017: 217-240.

  [3]. Carder E J. Synthetic Efforts toward p97 AAA+ ATPaseand p75 Neurotrophin Receptor Inhibitors[D]. University of Pittsburgh, 2019.