AH-001 / AnHorn Medicines - LARVOL DELTA

Discovery of 1,2-Diol TRPV4 Antagonists with Efficacy in a 3D Myocardial Fibrosis Organoid Model and a Murine TAC Pressure-Overload Model. (PubMed, J Med Chem) - "Herein, starting from our reported vicinal-diol TRPV4 antagonist AH001, we performed structure-guided optimization to generate a focused series of active analogues...In vivo, compound 26 improved cardiac function and attenuated adverse remodeling in a murine transverse aortic constriction (TAC) pressure-overload model. Together, these findings support compound 26 as a promising candidate for the treatment of cardiac fibrosis."

Journal • Preclinical • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology

AH001: A New Drug Targeting RhoA in Heart Failure. (PubMed, Circ Res) - No abstract available

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Inflammation • RHOA

Inhibiting RhoA Activation Via GDP-State Stabilization to Relieve Heart Failure. (PubMed, Circ Res) - "Consequently, AH001 markedly attenuated myocardial remodeling in multiple HF animal models, as well as in 3-dimensional myocardial tissue models. These findings establish pharmacological inhibition of RhoA activation as a viable strategy to mitigate myocardial remodeling in HF and provide a conceptual framework for developing reversible inhibitors against previously undruggable small GTPases."

Clinical • Journal • Retrospective data • Review • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • GDI1 • MRTFA • RHOA

Discovery of the microtubule-severing protein as the target of antifungal compound heat-stable antifungal factor in Fusarium graminearum and rational design of novel inhibitors. (PubMed, Pest Manag Sci) - "This study demonstrates that HSAF exerts its antifungal activity against F. graminearum by targeting the microtubule-severing protein FGSG_09851. Guided by this mechanism, we designed and synthesized novel AAA+ ATPase inhibitors with promising antifungal activity. These findings elucidate the mode of action of HSAF and establish microtubule-severing proteins as a promising target class for fungicide development."

Journal

Evaluation of the Safety, Tolerability and Pharmacokinetics of AH-001 Following Topical Single and Multiple Ascending Dose Administration (clinicaltrials.gov) - P1 | N=64 | Completed | Sponsor: AnHorn Medicines Co. Ltd. | Recruiting ➔ Completed

Trial completion • Alopecia • Dermatology • Immunology

Expanding the Scope of PROTACs: Opportunities and Challenges in Topical Delivery. (PubMed, J Med Chem) - "This miniperspective highlights key advances in the development of topical PROTACs, exemplified by AH-001 and GT20029, androgen receptor degraders, both in clinical trials for androgenetic alopecia, with GT20029 also evaluated for acne. Despite this progress, topical PROTACs face some challenges, such as optimizing the stability, tissue penetration, and selective target engagement under physiological conditions. We conclude by outlining strategic directions that could accelerate the clinical translation of this emerging therapeutic modality."

Journal • Review • Acne Vulgaris • Alopecia • Dermatology • Immunology • Ophthalmology • Targeted Protein Degradation • AR

Inactivation of RhoA for Hypertension Treatment Through the TRPV4-RhoA-RhoGDI1 Axis. (PubMed, Circulation) - "TRPV4 and RhoGDI1 knockdown attenuated AH001's inhibition of VSMC contraction and phenotypic switching to myofibroblasts. This study revealed a novel mode of RhoA signaling inhibition targeting the TRPV4-RhoA-RhoGDI1 axis, offering new insights for future antihypertensive drug development and proposing innovative strategies for targeting challenging Rho GTPases."

Journal • Cardiovascular • Hypertension • GDI1 • MRTFA • RHOA

Evaluation of the Safety, Tolerability and Pharmacokinetics of AH-001 Following Topical Single and Multiple Ascending Dose Administration (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: AnHorn Medicines Co. Ltd.

New P1 trial • Alopecia • Dermatology • Immunology