Colorectal cancer (CRC) is a common malignancy of the gastrointestinal tract, often accompanied by poor prognosis and high incidence and mortality. p21 activated kinases (PAKs) have been used as therapeutic targets because of their central role in many oncogenic signaling networks. By exploring tumor databases, we found that PAK1 overexpression is associated with poor prognosis in colorectal cancer, and therefore, PAK1‐targeted inhibition is a new potential therapeutic strategy for colorectal cancer. We identified that Balanol (compound 6, DB04098) can effectively target PAK1 by high‐throughput virtual screening. In vitro, compound 6 exhibited favorable PAK1 inhibition with potent anti‐proliferative and anti‐migration activity in SW480 cells. Additionally, we also found that compound 6 induced apoptosis and cytoprotective autophagy in SW480 cells. Together, these results indicate that compound 6 is a potential novel PAK1 inhibitor, which would be utilized as a candidate compound for future CRC treatment.

01 Feb 2022·CURRENT ORGANIC SYNTHESISQ4 · CHEMISTRY

Comprehensive Account on the Synthesis of (-)-Balanol and its Analogues

Q4 · CHEMISTRY

Review

Author: Ahmad, Sajjad ; Zahoor, Ameer Fawad ; Akhtar, Rabia

Background::

A variety of diseases have been associated with hyperactivation of protein kinase C (PKC) enzymes such as cancer, diabetes, asthma, cardiovascular and central nervous system disorders. There is a dire need to selectively inhibit these enzymes by synthesizing new potent inhibitors. Balanol, a fungal metabolite belonging to the PKC inhibitor family, is especially included in this aspect. Tremendous effort has been put towards the synthesis of balanol by different research groups.

Objective::

The aim of this review is to provide a detailed description of synthetic approaches adopted for the synthesis of key fragments of balanol (azepane and benzophenone). All the factors that resulted in excellent yield and high enantioselectivity have also been mentioned.

Conclusion::

It has been shown throughout this review that the synthesis of hexahydroazepine and benzophenone cores of balanol was achieved by employing a variety of important key steps with commercially available starting precursors, which make this total synthesis more valuable. Moreover, this article provides ideas to the synthetic as well as pharmaceutical chemists for the synthesis of (-)-balanol and its analogues.

01 Feb 2019·BMC bioinformatics

Diverse dynamics features of novel protein kinase C (PKC) isozymes determine the selectivity of a fluorinated balanol analogue for PKCε

Article

Author: Ranganathan, Shoba ; Hardianto, Ari ; Liu, Fei ; Khanna, Varun

BACKGROUND:

(-)-Balanol is an ATP-mimicking inhibitor that non-selectively targets protein kinase C (PKC) isozymes and cAMP-dependent protein kinase (PKA). While PKA constantly shows tumor promoting activities, PKC isozymes can ambiguously be tumor promoters or suppressors. In particular, PKCε is frequently implicated in tumorigenesis and a potential target for anticancer drugs. We recently reported that the C5(S)-fluorinated balanol analogue (balanoid 1c) had improved binding affinity and selectivity for PKCε but not to the other novel PKC isozymes, which share a highly similar ATP site. The underlying basis for this fluorine-based selectivity is not entirely comprehended and needs to be investigated further for the development of ATP mimic inhibitors specific for PKCε.

RESULTS:

Using molecular dynamics (MD) simulations assisted by homology modelling and sequence analysis, we have studied the fluorine-based selectivity in the highly similar ATP sites of novel PKC (nPKC) isozymes. The study suggests that every nPKC isozyme has different dynamics behaviour in both apo and 1c-bound forms. Interestingly, the apo form of PKCε, where 1c binds strongly, shows the highest degree of flexibility which dramatically decreases after binding 1c.

CONCLUSIONS:

For the first time to the best of our knowledge, we found that the origin of 1c selectivity for PKCε comes from the unique dynamics feature of each PKC isozyme. Fluorine conformational control in 1c can synergize with and lock down the dynamics of PKCε, which optimize binding interactions with the ATP site residues of the enzyme, particularly the invariant Lys437. This finding has implications for further rational design of balanol-based PKCε inhibitors for cancer drug development.

100 Deals associated with Balanol

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Inflammation	Preclinical	United States	Triangle Research Labs LLC	-
Neoplasms	Preclinical	United States	Triangle Research Labs LLC	-
Psoriasis	Preclinical	United States	Triangle Research Labs LLC	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

Balanol

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation