Enamine’s covalent fragments produce potent and unique hits
In a recent JACS paper several academic groups collaborated on discovery of novel covalent inhibitors using a library of 993 acrylamides and chloroacetamides sourced from Enamine’s covalent fragment collection. The design was focusing on mild electrophiles that were supposed to overcome the selectivity challenge. The library was characterized by a new high-throughput thiol-reactivity assay and screened against 10 cysteine-containing proteins. Potent and unique primary hits have been found in the majority (7 out of 10) of cases.
A refined library used in the research with a few frequent hitters and excessively reactive fragments removed is available from Enamine on request >
Ref.: J. Am. Chem. Soc. 2019, 141, 8951−8968
Reach out to new chemical space breaking the availability bias: 11 000 000 000 molecules and beyond
Atomwise and Enamine to Advance Pediatric Oncology With the World’s First and Largest Ten Billion Compound Virtual Screen
10 Billion REAL compounds will be searched using AI powered drug screening platform to find novel small molecules for the treatment of pediatric cancers. In collaboration with academic researchers, Atomwise and Enamine said the “10-to-the-10 program” will seek to maximize the opportunity to develop drugs for new target proteins to inhibit cancer growth and metastasis. Read PRESS RELEASE >
The world’s largest collection of building blocks in stock: 174 123 and counting
In a recent JACS paper several academic groups collaborated on discovery of novel covalent inhibitors using a library of 993 acrylamides and chloroacetamides sourced from Enamine’s covalent fragment collection. The design was focusing on mild electrophiles that were supposed to overcome the selectivity challenge. The library was characterized by a new high-throughput thiol-reactivity assay and screened against 10 cysteine-containing proteins. Potent and unique primary hits have been found in the majority (7 out of 10) of cases.
Atomwise, Enamine, and top university researchers collaborate to discovery novel small molecules for the treatment of pediatric cancers using the power of AI and novel chemistry.
Enamine and H. Lundbeck A/S (Lundbeck) announced the expansion of their research collaboration. Enamine will support Lundbeck’s in-house discovery chemistry competencies with three principal assets enabling Lundbeck to optimally identify and develop hit series in its multiple research programs. A large diverse library of 100 000 new screening compounds was done for hit finding activities on numerous therapeutic targets. Enamine’s make-on-demand REAL compounds are for efficient access to billions of novel chemical compounds. Enamine FTE increased dedicated team of chemists to effectively support Lundbeck on all hit related follow-up activities backed by immediate access to over 170 000 building blocks in Enamine’s inventory.
Enamine is a global supplier driven by people with passion to Chemistry. Over twenty years we have been committed to serving our customers in diversified markets ranging from screening libraries discovery to building blocks for medicinal chemistry and biological screening services. In order to meet their high expectations, we have gathered a team of motivated chemists and biologists and equipped our numerous labs and production facilities with state of the art equipment and quality control systems. We are constantly developing to address the challenges of dynamically evolving drug discovery industry.
With the thought of our customers, we have adopted high level of business process automation and resource management to timely deliver products of highest quality and competitive prices. Over the years we have created smart IT systems simplifying life for our employees and making business more efficient.
Wnt/sFRP-1 Interaction Inhibitors Library
#
1 346 compounds
This selection of small molecules takes into consideration Wnt/sFRP-1 (Secreted Frizzled Related Proteins) interaction. sFRP-1 family of proteins include endogenous molecules that bind both Wnt ligands and Fz receptors.
Fig. 1.Epigenetic inactivation of negative regulators of WNT signaling. (a) In cancer cells, epigenetic inactivation of SFRP and DKK enables β-catenin to translocate to the nucleus, which leads to activation of WNT signaling. (b) In normal cells, SFRP and DKK are associated with key WNT signaling molecules such as WNT ligands and LRP5/6, which prevent translocation of β-catenin to the nucleus (from
Tohoku J. Exp. Med.2010, 221, 11–17).
It is believed that inhibition of sFRP-1 would result in vicarious activation of Wnt signaling. In adition, WAY-316606 is a sFRP-1 inhibitor (K
i= 80 nM) that was described to increase total bone area in a murine calvarial organ culture assay at < 1 nM concentration. It is also reported to be antiosteoporotic agent. WAY-262611 is a Wnt pathway agonist that increases bone formation rate with EC
50 of 0.63 uM in TCF-Luciferase assay. WAY-262611 exhibits good pharmacokinetic properties and a dose dependent increase in the trabecular bone formation rate in ovariectomized rats following oral administration. Specific attention needs to be paid to monitoring specific organ toxicity associated with a long-term perturbation of Wnt pathway including neoplasia(s), although recent data suggest otherwise. Current (sub)library size is 1 346 compounds.
Fig. 2.(a) Pharmacophore model based on WAY-316606; orange – aromatic/heteroaromatic groups, green-hydrophobic pharmacophore (halogen, CF
3, CHF
2, Me, Et, iPr
etc.), blue-positively charged moiety (
+NH
3Alk,
+NH
2Alk
2,
+NHAlk
3etc.);
(b) Superposition of WAY-316606 and our pharmacophore construct used in (sub)library design.
[submenu-wnt-lib][/submenu-wnt-lib]
FOLLOW US
E-newsletter
Thank you! Please check your email and confirm the newsletter subscription.
Your subscription was updated
Request product information
Please leave your request for any product you wish. We will be happy to search it for you in our databases or offer its custom synthesis
Video:
