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8gbu

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Hepatitis B capsid Y132A mutant with compound AB-506

Structural highlights

8gbu is a 6 chain structure with sequence from Hepatitis B virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.5Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

Disruption of the HBV capsid assembly process through small-molecule interaction with HBV core protein is a validated target for the suppression of hepatitis B viral replication and the development of new antivirals. Through combination of key structural features associated with two distinct series of capsid assembly modulators, a novel aminochroman-based chemotype was identified. Optimization of anti-HBV potency through generation of SAR in addition to further core modifications provided a series of related functionalized aminoindanes. Key compounds demonstrated excellent cellular potency in addition to favorable ADME and pharmacokinetic profiles and were shown to be highly efficacious in a mouse model of HBV replication. Aminoindane derivative AB-506 was subsequently advanced into clinical development.

Design, synthesis, and structure-activity relationship of a bicyclic HBV capsid assembly modulator chemotype leading to the identification of clinical candidate AB-506.,Cole AG, Kultgen SG, Mani N, Quintero JG, Yi Fan K, Ardzinski A, Stever K, Dorsey BD, Phelps JR, Lee ACH, Thi EP, Chiu T, Tang S, Horanyi PS, Mayclin SJ, Harasym TO, Sofia MJ Bioorg Med Chem Lett. 2023 Oct 1;94:129456. doi: 10.1016/j.bmcl.2023.129456. Epub , 2023 Aug 25. PMID:37633618^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Cole AG, Kultgen SG, Mani N, Quintero JG, Yi Fan K, Ardzinski A, Stever K, Dorsey BD, Phelps JR, Lee ACH, Thi EP, Chiu T, Tang S, Horanyi PS, Mayclin SJ, Harasym TO, Sofia MJ. Design, synthesis, and structure-activity relationship of a bicyclic HBV capsid assembly modulator chemotype leading to the identification of clinical candidate AB-506. Bioorg Med Chem Lett. 2023 Aug 24:129456. PMID:37633618 doi:10.1016/j.bmcl.2023.129456