Delving into the Latest Updates on HAO472 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

AML1-ETO

Action

inhibitors

Mechanism

AML1-ETO inhibitors

Therapeutic Areas

NeoplasmsHemic and Lymphatic Diseases

Active Indication

Acute Myeloid Leukemia

Inactive Indication-

Originator Organization

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Active Organization

Ruijin Hospital

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Inactive Organization-

Drug Highest PhasePhase 1

First Approval Date-

RegulationSpecial Review Project (China)

Login to view timeline

Primary objective: To determine the maximum tolerated dose (MTD) of HAO472 for the treatment of relapsed/refractory M2b AML. Secondary objectives: 1) To evaluate the safety and tolerability of the drug; 2) To investigate the pharmacokinetic characteristics of HAO472 in humans; 3) To preliminarily explore the effectiveness of HAO472 in the treatment of relapsed/refractory M2b AML.

Start Date-

Sponsor / Collaborator

Ruijin Hospital

[+2]

100 Clinical Results associated with HAO472

Login to view more data

100 Translational Medicine associated with HAO472

Login to view more data

100 Patents (Medical) associated with HAO472

Login to view more data

5

Literatures (Medical) associated with HAO472

01 Mar 2022·ACS OmegaQ3 · CHEMISTRY

Binding Studies of the Prodrug HAO472 to SARS-Cov-2 Nsp9 and Variants

Q3 · CHEMISTRY

ArticleOA

Author: Rossjohn, Jamie ; Quinn, Ronald J ; Liu, Miaomiao ; Littler, Dene R.

SARS-CoV-2 (COVID-19) has infected over 219 million people and caused the death of over 4.55 million worldwide. In a previous screen of a natural product library against purified SARS-CoV-2 Nsp9 using a native mass spectrometry-based approach, we identified an ent-kaurane natural product, oridonin (1), with micromolar affinities. In this work, we have found that the prodrug HAO472 (2) directly binds to Nsp9, establishing replacement of the labile ester with a bioisostere as a candidate drug strategy. We further tested 1 and its clinical analogue 2 against two Nsp9 variants from human coronavirus 229E (HCoV-229E) and ferret systemic coronavirus F56 (FSCoV-F56). Both compounds showed significant binding selectivity to COVID-19 and HCoV-229E Nsp9 over FSCoV-F56 Nsp9, confirming the covalent bond with Cys73.

11 May 2020·Mini-Reviews in Medicinal ChemistryQ3 · MEDICINE

Recent Progress of Oridonin and Its Derivatives for the Treatment of Acute Myelogenous Leukemia

Q3 · MEDICINE

Review

Author: Zang, Linghe ; Hu, Xu ; Hua, Huiming ; Xiao, Yan ; Xu, Shengtao ; Xu, Jinyi ; Wang, Yan ; Gao, Xiang ; Li, Zhanlin ; Li, Dahong

First stage human clinical trial (CTR20150246) for HAO472, the L-alanine-(14-oridonin) ester trifluoroacetate, was conducted by a Chinese company, Hengrui Medicine Co. Ltd, to develop a new treatment for acute myelogenous leukemia. Two patents, WO2015180549A1 and CN201410047904.X, covered the development of the I-type crystal, stability experiment, conversion rate research, bioavailability experiment, safety assessment, and solubility study. HAO472 hewed out new avenues to explore the therapeutic properties of oridonin derivatives and develop promising treatment of cancer originated from naturally derived drug candidates. Herein, we sought to overview recent progress of the synthetic, physiological, and pharmacological investigations of oridonin and its derivatives, aiming to disclose the therapeutic potentials and broaden the platform for the discovery of new anticancer drugs.

01 Jun 2019·European Journal of Medicinal ChemistryQ1 · MEDICINE

Effective enmein-type mimics of clinical candidate HAO472: Design, synthesis and biological evaluation

Q1 · MEDICINE

Article

Author: Hu, Xu ; Xu, Jinyi ; Xu, Yongnan ; Wang, Xianhua ; Hua, Huiming ; Bai, Ziyi ; Qiao, Jian ; Xu, Shengtao ; Li, Dahong ; Li, Haonan

A series of enmein-type diterpenoid amino acid ester derivatives (14-22) were designed and synthesized according to l-alanine-(14-oridonin) ester trifluoroacetate (clinical candidate HAO472). Their antiproliferative activities were tested against SGC-7901, Bel-7402, HL-60, PC-3, A549 and K562 cancer cell lines and L-02 normal liver cells. The results showed that compound 19 possessed the most potent cytotoxicity with IC₅₀ s at sub-micromolar level against human hepatoma Bel-7402 and chronic myelogenous leukemia K562 cells and more potent than l-alanine-(14-oridonin) ester (23). More importantly, 19 displayed 70-fold less cytotoxicity than parent 3 (IC₅₀ = 25.47 μM) against L-02 cells, which exhibited certain selectivity. Further mechanism study in Bel-7402 cells revealed that 19 could induce apoptosis, G₁ phase cell cycle arrest and mitochondrial dysfunction. Western blot results of caspase-3, Bax and cytochrome c upregulation and pro-caspase-3, Bcl-2 and Bcl-xL downregulation confirmed the intrinsic pathways. Overall, these data collectively demonstrated the high efficiency and selectivity of 19, l-phenylalanine-enmein-type diterpenoid ester, which inspires further and effective application as a potential antitumor candidate.

100 Deals associated with HAO472

Login to view more data