$29.97
- Mechanism: Water-soluble prodrug; Dihexa binds to HGF and modifies the structure, significantly potentiating HGF’s efficacy at the c-MET receptor
- 100 mcg Dihexa Phosphate Ester per 0.1 mL spray, 10 mL total (10,000 mcg)
- Contains 0.25% Dodecyl Maltoside, 0.5% PLX-188, and 20% PG
- Estimated 100 sprays research supply
Description
Fixing the problems of Dihexa with a water-soluble prodrug
- Unfortunately, since Dihexa isn’t water-soluble and has low oral bioavailability as an expensive molecule, it’s heavily limited by incovenient and suboptimal routes of administration like transdermal DMSO
- The study is redacted, but is potentially true; Dihexa binds to HGF with extremely high affinity (Kd = 65 pM), as it’s in the pM range [x]
- Dihexa Phosphate Ester (Fosgonimeton or ATH-1017) is a water-soluble prodrug and the active metabolite is Dihexa (ATH-1001)
- Despite a study saying Dihexa has a >12 day half-life in rats, Dihexa actually has a 1.5 h half-life in humans and the Phosphate Ester prodrug has a 0.3 h half-life [x, x]
- Since Dihexa Phosphate Ester is water-soluble, the intranasal route targets the CNS and is effective in the mcg range, significantly lower than other routes of administration with normal Dihexa which is effective in the mg range
Athira Pharma’s HGF potentiator series
- Athira Pharma has two more candidates in their HGF potentiator series, other than Dihexa and Dihexa Phosphate Ester
- ATH-1020 is potentially an orally available Dihexa prodrug, as it’s their only other patented molecule, but it’s impossible to be certain which compound it is from public information. ATH-1020 isn’t a good option, a lot of it will be wasted peripherally, since HGF is also outside the CNS and Dihexa is too expensive to make this cost-effective [x]
- ATH-1105 is orally available and is their latest candidate, it has a shorter half-life of 0.78 h in mice. The structure is either compound 1A or 5A in their patent [x, x]
