Drug intelligence / Profile preview

withanolide D

Development stage
Preclinical
Lead developer
University of Arizona
Modality
Orthosteric Ligands → Classical Binding Small Molecules → Small Molecules, Nucleic Acid-Directed Small Molecules → Small Molecules
Administration
Oral, Topical (as Plant Extract; Purified Drug Route Unestablished)
01

Overview

**Withanolide D** is a naturally occurring steroidal lactone, part of the withanolide class, most notably isolated from the plant *Withania somnifera* (Ashwagandha). It is structurally characterized as a C28 steroid with an ergostane skeleton and a lactone ring, as given by its molecular formula C28H38O6 and molecular weight 470.6. Preclinical studies have demonstrated that withanolide D exhibits potent anticancer properties, notably inducing cytostatic effects and apoptosis in both drug-resistant and drug-sensitive multiple myeloma and leukemia cells at nanomolar concentrations. Its mechanism involves induction of apoptotic cell death and likely modulation of oxidative stress (ROS) pathways, cell cycle disturbance, inhibition of non-homologous end-joining DNA repair, and possible influence on NF-κB signaling. In animal models, it reduces tumor growth and does not appear to inhibit P-glycoprotein (P-gp), indicating efficacy even in drug-resistant tumors. Withanolide D is also being explored for potential benefits in inflammatory and autoimmune diseases due to anti-inflammatory and immunomodulatory effects, although human clinical data and regulatory approvals are lacking[1][3][4][5][6].

Other names
(20R,22R)-4β,20-dihydroxy-5β,6β:22,26-diepoxyergosta-2,24-diene-1,26-dione(22R)-5,6β-epoxy-4β,20,22-trihydroxy-1-oxo-5β-ergosta-2,24-dien-26-oic acid δ-lactone
02

Targets

ATM (Ataxia-telangiectasia mutated)DNA-PK (DNA-dependent protein kinase)XRCC4

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