atrasentan

Atrasentan (ABT-627/A-127722) is an ETA receptor antagonist that was originally discovered by Abbott (AbbVie) in the 1990s to treat prostate cancer. Unfortunately, clinical data with the compound in prostate cancer was insufficient for approval, and AbbVie pivoted the compound to chronic kidney diseases instead, ultimately conducting a large, 5,000+ patient trial (SONAR) that was published in 2019.

Atrasentan (ABT-627/A-127722) is an ETA receptor antagonist that was originally discovered by Abbott (AbbVie) in the 1990s to trea...

TP0472993

The arachidonic acid (AA) metabolite, 20-hydroxy-5,8,11,14-eicosatetranoic acid (20-HETE), has been extensively studied as a modulator of kidney function and a mediator of kidney diseases over decades. The receptor for 20-HETE, the G-coupled protein receptor GPR75, was only recently identified (2017), and GPR75/20-HETE pathway modulators are of industry interest in many disease areas including obesity (e.g. 2020 Regeneron patent filing) and kidney diseases (e.g. 2018 Taisho patent filing).

The arachidonic acid (AA) metabolite, 20-hydroxy-5,8,11,14-eicosatetranoic acid (20-HETE), has been extensively studied as a modul...

daprodustat

The first and only HIF prolyl hydroxylase inhibitor approved in the US. Erythropoetin (EPO) stimulates red blood cell production (erythropoeisis). Recombinant erythropoetin (e.g. Amgen’s epoetin alfa ) is therefore a treatment for anemia (lack of healthy red blood cells) and was one of the first biotech products to be approved (in 1989) and [...]

The first and only HIF prolyl hydroxylase inhibitor approved in the US. Erythropoetin (EPO) stimulates red blood cell production (...

sparsentan

An old BMS program revitalized as a first-in-class drug in a new indication. Despite Travere Therapeutics having a checkered industry history due to ties to Martin Shrkeli, there appears to be potentially differentiating efficacy for sparsentan’s ( Filspari ) accelerated approval thanks to its novel dual-antagonistic mechanism. It’s also [...]

An old BMS program revitalized as a first-in-class drug in a new indication. Despite Travere Therapeutics having a checkered indus...

Terlipressin: Longer Peptide Effect Half-Life via an Active Metabolite

On Monday, Mar. 27th (12:15 PM ET), our Drug Hunter team will be sponsoring a luncheon at ACS Spring 2023 in Indianapolis with a presentation on scientific gems from 2022’s drug approvals ( request an invitation here ). Each newly approved drug has an interesting scientific story, and you can see our overview of all 36 of the novel small [...]

On Monday, Mar. 27th (12:15 PM ET), our Drug Hunter team will be sponsoring a luncheon at ACS Spring 2023 in Indianapolis with a p...

BI 685509

A newly disclosed sGC activator in Ph. II for CKD/DKD. This month, researchers at BI reported promising preclinical results for a newly disclosed sGC activator, BI-685509, which is in several Ph. II trials including for treatment of chronic kidney disease (CKD) and diabetic kidney disease (DKD) ( NCT04736628 , NCT04750577 ). In rodents, the [...]

A newly disclosed sGC activator in Ph. II for CKD/DKD. This month, researchers at BI reported promising preclinical results for a ...

vadadustat

Context. Vadadustat (Akebia Therapeutics) is an oral hypoxia-inducible factor prolyl-4-hydroxylase domain (HIF-PHD) inhibitor being developed for anemia in patients with chronic kidney disease (CKD). HIFs are transcription factors that mediate the expression of target genes, including for erythropoietin (EPO). In CKD, inhibition of PHDs , a [...]

Context. Vadadustat (Akebia Therapeutics) is an oral hypoxia-inducible factor prolyl-4-hydroxylase domain (HIF-PHD) inhibitor bein...

2021 FDA Endocrinology Approvals: Novel Small Molecules Deep Dive

In 2021, the FDA approved two new drugs for endocrinology-related indications, including severe hypoglycemia in diabetes, and chronic kidney disease (CKD) associated with type 2 diabetes. This article and slide deck explores each in more detail, including but not limited to their: target rationale discovery disease context original patents [...]

In 2021, the FDA approved two new drugs for endocrinology-related indications, including severe hypoglycemia in diabetes, and chro...

"Compound 19" (iron-binder)

“Compound 19” (iron-binder) is an oral inhibitor of the hypoxia-inducible factor (HIF) propyl hydroxylase domain (HIF-PHD), increasing HIF levels to activate EPO transcription and promote hematopoiesis for treatment of anemia. Interestingly, this compound is modeled to make a bi-dentate interaction with an iron co-factor of HIF-PHD via a [...]

“Compound 19” (iron-binder) is an oral inhibitor of the hypoxia-inducible factor (HIF) propyl hydroxylase domain (HIF-PHD), increa...

“Compound 9”

“Compound 9” is the first potent M3-selective positive allosteric modulator, with potential utility as a biological tool compound. It does have secondary activity against M5 at high doses though. It’s quite a large zwitterion, which is somewhat unusual for GPCRs.

“Compound 9” is the first potent M3-selective positive allosteric modulator, with potential utility as a biological tool compound....