Delving into the Latest Updates on I-022 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

N-(4-(1-cyclopropyl-4-fluoro-2-methyl-1H-benzo[d]imidazol-6-yl)-5-fluoropyrimidin-2-yl)-6-(2-(dimethylamino)ethyl-5,6,7,8-tetrahydro-1,6-naphthyridin-2-amine maleate, I 022, I022

+ [1]

Target

CDK4 x CDK6

Mechanism

CDK4 inhibitors(Cyclin-dependent kinase 4 inhibitors), CDK6 inhibitors(Cyclin-dependent kinase 6 inhibitors)

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal DiseasesNervous System Diseases+ [1]

Active Indication

Locally advanced breast cancerBrain metastasesLiposarcoma+ [7]

Inactive Indication

Dedifferentiated LiposarcomaHormone receptor positive HER2 negative breast cancerMetastatic breast cancer+ [1]

Originator Organization

Shanghai Pharmaceuticals Holding Co., Ltd.

Active Organization

Shanghai Pharmaceuticals Holding Co., Ltd.SPH (Benxi) North Pharmaceutical Co., Ltd.

Inactive Organization

Shanghai Pharma Biotherapeutics Usa, Inc.

Shanghai Pharmaceutical Group (Benxi) North Pharmaceutical Co., Ltd.

Drug Highest PhasePhase 2/3

First Approval Date-

RegulationOrphan Drug (US)

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Protoporphyrinogen IX oxidase (PPO, E.C. 1.3.3.4) plays a pivotal role in chlorophyll biosynthesis in plants, making it a prime target for herbicide development. In this study, we conducted an investigation aimed at discovering PPO-inhibiting herbicides. Through this endeavor, we successfully identified a series of novel compounds based on the pyridazinone scaffold. Following structural optimization and biological assessment, compound 10ae, known as ethyl 3-((6-fluoro-5-(6-oxo-4-(trifluoromethyl)pyridazin-1(6H)-yl)benzo[d]thiazol-2-yl)thio)propanoate, emerged as a standout performer. It exhibited robust activity against Nicotiana tabacum PPO (NtPPO) with an inhibition constant (K_i) value of 0.0338 μM. Concurrently, we employed molecular simulations to obtain further insight into the binding mechanism with NtPPO. Additionally, another compound, namely, ethyl 2-((6-fluoro-5-(5-methyl-6-oxo-4-(trifluoromethyl)pyridazin-1(6H)-yl)benzo[d]thiazol-2-yl)thio)propanoate (10bh), demonstrated broad-spectrum and highly effective herbicidal properties against all six tested weeds (Leaf mustard, Chickweed, Chenopodium serotinum, Alopecurus aequalis, Poa annua, and Polypogon fugax) at the dosage of 150 g a.i./ha through postemergence application in a greenhouse. This work identified a novel lead compound (10bh) that showed good activity in vitro and excellent herbicidal activity in vivo and had promising prospects as a new PPO-inhibiting herbicide lead.

01 Apr 2023·Surgery

Different routes of administering EW-7197 versus EW-7197⋅HBr for preventing peritoneal adhesion in a rat model

Article

Author: Won, Dong-Sung ; Kim, Song Hee ; Kim, Ji Won ; Park, Yubeen ; Kim, Dae-Kee ; Kang, Jeon Min ; Ryu, Dae Sung ; Shin, Ji Hoon ; Shim, Soyeon ; Zeng, Chu Hui ; Park, Jung-Hoon

BACKGROUND:

The relatively low aqueous solubility of EW-7197 that was administered orally may have affected the desired concentration in the systemic circulation for treating peritoneal adhesion. This experimental study aimed to compare the efficacy of different routes of administering EW-7197 (2-fluoro-N-[(5-[6-methylpyridin-2-yl]-4-[(1,2,4)triazolo(1,5-a)pyridin-6-yl]-1H-imidazol-2-yl)methyl]aniline) and EW-7197·hydrobromide (HBr), with improved aqueous solubility, for inhibiting peritoneal adhesion in a rat model.

METHODS:

After peritoneal adhesion induction, 30 male Sprague-Dawley rats were randomly divided into 5 groups with 6 rats in each: group A, sham control; group B, orally administered 25 mg/kg of EW-7197·HBr for 7 days; group C, locally administered 25 mg/kg of EW-7197·HBr; group D, orally administered 20 mg/kg of EW-7197 for 7 days; and group E, locally administered 20 mg/kg of EW-7197. Gross examination, histologic staining (hematoxylin and eosin and Masson's trichrome), and immunohistochemical analyses (Ki-67 and α-smooth muscle actin marker [α-SMA]) were performed to evaluate the efficacy of both drugs.

RESULTS:

All procedures were technically successful. All treatment groups, except for group C, showed significantly reduced incidence, quality, tenacity, fibrosis, and collagen deposition scores and lowered expressions of Ki-67- and α-SMA-positive cells compared with group A. When comparing between groups, all scores were significantly lower in group B than in group C (all P < .001), whereas no significant difference was noted in any of the scores between groups D and E and groups B and E (all P > .05).

CONCLUSION:

Orally administering EW-7197·HBr and both orally and locally administering EW-7197 significantly prevented peritoneal adhesion formation, and orally administering EW-7197·HBr was the most effective overall.

01 Dec 2020·Journal, genetic engineering & biotechnology

Screening and optimization of indole-3-acetic acid production by Rhizobium sp. strain using response surface methodology

Article

Author: Fikri-Benbrahim, Kawtar ; Fadil, Mouhcine ; Lebrazi, Sara ; Chraibi, Marwa

Abstract:

Background:

The production of indole-3-acetic acid (IAA) is an essential tool for rhizobacteria to stimulate and facilitate plant growth. For this, eighty rhizobial bacteria isolated from root nodules of Acacia cyanophylla grown in different regions of Morocco were firstly screened for their ability to produce IAA. Then, IAA production by a combination of isolates and the inoculation effect on the germination of Acacia cyanophylla seeds was studied using the best performing isolates in terms of IAA production. The best IAA producer bacterial isolate (I69) was selected to optimize IAA production using response surface methodology based on the central composite design.

Results:

Results showed that the majority of tested isolates were able to produce IAA with a relatively higher concentration of 135 μg/ml for the isolate I69, followed by isolates I22 and I75 with respective concentrations of 116 μg/ml and 105 μg/ml IAA. The IAA production and the seed germination rate were relatively increased by the synergistic effect of I69 and I22. Later, response surface methodology was used to determine optimal operating conditions leading to IAA production optimization. Thus, an incubation temperature of 36 °C, a pH of 6.5, an incubation time of 1 day, and respective tryptophan and NaCl concentrations of 1 g/l and 0.1 g/l were optimal parameters leading to 166 μg/ml IAA which was the maximal produced concentration.

Conclusion:

The present study highlighted that IAA-producing rhizobacteria could be harnessed to improve plant growth. Furthermore, their production can be easily controlled using response surface methodology, which represents a very useful tool for optimization.

100 Deals associated with I-022

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Locally advanced breast cancer	Phase 3	CN	Shanghai Pharmaceuticals Holding Co., Ltd.	08 Sep 2023
Hormone receptor positive HER2 negative breast cancer	Phase 3	CN	Shanghai Pharmaceuticals Holding Co., Ltd.	24 Apr 2023
Metastatic breast cancer	Phase 3	CN	Shanghai Pharmaceuticals Holding Co., Ltd.	24 Apr 2023
Advanced Liposarcoma	Phase 2	CN	Shanghai Pharmaceuticals Holding Co., Ltd.	17 Oct 2023
Brain metastases	Phase 2	CN	Shanghai Pharmaceuticals Holding Co., Ltd.	19 Sep 2023
PIK3CA mutation/HR-positive/HER2-negative Breast Cancer	Phase 2	CN	Shanghai Pharmaceuticals Holding Co., Ltd.	19 Sep 2023
Dedifferentiated Liposarcoma	Phase 2	US	Shanghai Pharma Biotherapeutics Usa, Inc.	31 Aug 2023
Advanced Malignant Solid Neoplasm	Phase 2	CN	Shanghai Pharmaceuticals Holding Co., Ltd.	03 Nov 2020
Liposarcoma	Phase 2	US	Shanghai Pharmaceuticals Holding Co., Ltd.	-
Solid tumor	Phase 2	US	Shanghai Pharmaceuticals Holding Co., Ltd.	-