Delving into the Latest Updates on H-1337 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

Mechanism

LRRK2 inhibitors(Leucine-rich repeat serine/threonine-protein kinase 2 inhibitors), PKD1 inhibitors(polycystin 1, transient receptor potential channel interacting inhibitors), PKN2 inhibitors(protein kinase N2 inhibitors)

+ [1]

Therapeutic Areas

Eye Diseases

Active Indication

Glaucoma 1, Open Angle, A

Inactive Indication-

Originator Organization

D. Western Therapeutics Institute, Inc.

Active Organization

D. Western Therapeutics Institute, Inc.

Inactive Organization

Allysta Pharmaceuticals, Inc.Startup

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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PURPOSETo perform a phase Ⅰ/Ⅱ evaluation of an H-1337 ophthalmic solution in subjects with primary open-angle glaucoma (POAG) or ocular hypertension (OHT).DESIGNThis was a phase I/II, randomized, double-masked, vehicle-controlled, dose-response study conducted at 6 private practice sites in the United States. The study was registered with clinicaltrials.gov as NCT03452033.PARTICIPANTSEighty-seven subjects with bilateral POAG or OHT were enrolled.METHODSAfter washout of ocular hypotensive medications as required, the subjects were randomized to receive either the H-1337 ophthalmic solution at 0.06%, 0.2%, and 0.6% or its vehicle twice daily unilaterally in the study eye for the first 3 days and then twice daily in both eyes from day 4 to 28.MAIN OUTCOME MEASURESThe primary efficacy end point was the mean change in intraocular pressure from baseline (day 0) for each group on day 28 at hour 4 compared with the vehicle.RESULTSIn the primary efficacy end point, i.e., mean change from the baseline on day 28 at hour 4, the mean change from the baseline was - 4.45 ± 3.801, - 5.16 ± 3.114, - 4.93 ± 3.110, and - 0.39 ± 2.355 in the 0.06%, 0.2%, and 0.6% H-1337 and vehicle groups, respectively. The difference between each active group and the vehicle group was statistically significant (P < 0.0001). Treatment-emergent adverse events (TEAEs) occurred in 49% of subjects who received H-1337 (range, 41% [0.2% arm]-64% [0.6% arm] across the H-1337 arms) and 18% of subjects who received the vehicle. The majority of TEAEs were mild in severity; 3 subjects who received H-1337 had a TEAE of moderate intensity (instillation site erythema, blurred vision, and muscle strain).CONCLUSIONSThe H-1337 ophthalmic solution showed clinically and statistically significant ocular hypotensive activity and was well tolerated, with a relatively low incidence of hyperemia.FINANCIAL DISCLOSURE(S)Proprietary or commercial disclosure may be found after the references.

01 Jan 2008·Molekuliarnaia genetika, mikrobiologiia i virusologiia

[Difference in amino acid sequences of B. afzelii P66 surface-exposed loop region].

Article

Author: Korenberg, E I ; Morozov, A V ; Gorelova, N B ; Fadeeva, I A

In the present work, we performed a phenotyping analysis of 45 B. afzelii 89-a.a. long amino acid sequences of 7 different allele variants, corresponding to the surface-exposed loop region of P66. 45 investigated isolates showed 5 phenotypically different variants; 2 phenotypically different variants of loop region, in particular, also showed mutations in the putative monoclonal antibody H1337 binding site; the similarity between the amino acid sequences taken from different variants is about 96.66% to 98.88%; in one natural locus up to 3 different phenotypes of P66 could circulate simultaneously.

CellsQ3 · BIOLOGY

The Isoquinoline-Sulfonamide Compound H-1337 Attenuates SU5416/Hypoxia-Induced Pulmonary Arterial Hypertension in Rats

Q3 · BIOLOGY

ArticleOA

Author: Sanada, Takayuki Jujo ; Sakao, Seiichiro ; Hidaka, Hiroyoshi ; Tatsumi, Koichiro ; Sumi, Kengo ; Naito, Akira ; Maruyama, Junko ; Zhang, Erquan ; Yoshida, Yoko ; Maruyama, Kazuo ; Shoji, Hiroki

Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure and right heart failure. Selective pulmonary vasodilators have improved the prognosis of PAH; however, they are not able to reverse pulmonary vascular remodeling. Therefore, a search for new treatment agents is required. H-1337 is an isoquinoline-sulfonamide compound that inhibits multiple serine/threonine kinases, including Rho-associated protein kinase (ROCK) and mammalian target of rapamycin (mTOR). Here, we investigated the effects of H-1337 on pulmonary hypertension and remodeling in the pulmonary vasculature and right ventricle in experimental PAH induced by SU5416 and hypoxia exposure. H-1337 and H-1337M1 exerted inhibitory effects on ROCK and Akt. H-1337 inhibited the phosphorylation of myosin light chain and mTOR and suppressed the proliferation of smooth muscle cells in vitro. H-1337 treatment also suppressed the phosphorylation of myosin light chain and mTOR in the pulmonary vasculature and decreased right ventricular systolic pressure and the extent of occlusive pulmonary vascular lesions. Furthermore, H-1337 suppressed aggravation of right ventricle hypertrophy. In conclusion, our data demonstrated that inhibition of ROCK and mTOR pathways with H-1337 suppressed the progression of pulmonary vascular remodeling, pulmonary hypertension, and right ventricular remodeling.

100 Deals associated with H-1337

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Glaucoma 1, Open Angle, A	Phase 2	US	D. Western Therapeutics Institute, Inc.	28 Aug 2023
Glaucoma, Open-Angle	Discovery	US	Allysta Pharmaceuticals, Inc.Startup	15 Mar 2018

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03452033 (CTgov)	Phase 1/2	Glaucoma, Open-Angle	87	H-1337 (H-1337 0.06%)	qzfpupfica(upqjzdtvfh) = tpyxyjzxwx cqojikqfen (vrrokmdikb, ozfbnmbylf - twvghbzyjc) View more	-	02 Aug 2021
				H-1337 (H-1337 0.2%)	qzfpupfica(upqjzdtvfh) = qosamqqsjw cqojikqfen (vrrokmdikb, yteksfedis - fqagxdubqy) View more
ARVO2015	Not Applicable	Wet age-related macular degeneration	-	H-1337	(cabqwjolke) = jpxphlclkc hhiemxtjon (znahgkoxjq ) View more	-	01 Jun 2015
				H-1337M1	(cabqwjolke) = odcikmiejb hhiemxtjon (znahgkoxjq ) View more
ARVO2015	Not Applicable	Ocular Hypotension	-	H-1337	(mixgsaplys) = kbaljigljz uhscxdvmll (zuhthoadfa )	-	01 Jun 2015