ZYIL 1

It's only fair to share...Flattr the authorPin on PinterestEmail this to someone
Buffer this pageDigg thisShare on FacebookShare on Google+Tweet about this on TwitterShare on LinkedInShare on YummlyShare on VKShare on RedditShare on StumbleUponPrint this pageShare on Tumblr

Z 1

CAS 2254433-37-7

Z 1

CAS 2254432-75-0

High probabilty

ZYIL 1

TWO PREDICTIONS

Cryopyrin-associated periodic syndromes

ZYIL-1 is an oral, small-molecule inhibitor of the NLRP3 inflammasome in phase II clinical development at Zydus (formerly known as Cadila Healthcare and Zydus Cadila) for the treatment of cryopyrin-associated periodic syndromes (familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and neonatal onset multi-systemic inflammatory disease (NOMID; also known as chronic infantile neurologic cutaneous articular syndrome (CINCA)).

https://clinicaltrials.gov/ct2/show/NCT05186051

Condition or disease  Intervention/treatment  Phase 2
Cryopyrin Associated Periodic Syndrome

ZYIL1 is expected to show benefit in patients with CAPS. The present study aims to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of ZYIL1 when administered to subjects with CAPS.This is a phase 2a, prospective, open-label study. Primary objective of the study is to determine safety and tolerability profile of twice daily oral administration of ZYIL1 administered for 7 days. The study will be conducted in 3 subjects having CAPS as per eligibility criteria. The study will be divided in three periods: Screening Period; Run-in Period and Study Period.

Zydus announces positive Phase 2 Proof-of-Concept of NLRP3 inhibitor, ZYIL1 in patients with Cryopyrin Associated Periodic Syndrome (CAPS)

https://pipelinereview.com/index.php/2022090781551/Small-Molecules/Zydus-announces-positive-Phase-2-Proof-of-Concept-of-NLRP3-inhibitor-ZYIL1-in-patients-with-Cryopyrin-Associated-Periodic-Syndrome-CAPS.html

First Phase 2 Proof-of-Concept (POC) study demonstrating rapid clinical improvement and remission within days when Cryopyrin Associated Periodic Syndrome (CAPS) patients with flare ups were treated with ZYIL1, a novel oral small molecule NLRP3 inhibitor

Phase 1 study in Healthy Human volunteers published in “Clinical Pharmacology in Drug Development” Journal of American College of Clinical Pharmacology

AHMEDABAD, India I September 07, 2022 I Zydus Lifesciences Ltd. (formerly known as Cadila Healthcare Ltd.), a discovery-driven, global lifesciences company today announced that it has achieved a positive Proof-of-Concept in its Phase 2 clinical study of ZYIL1, in patients with CAPS.

CAPS is a rare, life-long, auto-inflammatory condition, caused by NLRP3 activating mutations and is classified as an orphan disease. The chronic inflammation due to IL-1beta release in CAPS patients leads to urticaria-like rash, fever, arthralgia, and increased risk of amyloidosis. CAPS patients also experience multiple neurological complications like sensorineural hearing loss, migraine, headache, aseptic meningitis and myalgia. Bone deformities and neurological impairments have been reported in Neonatal Onset Multisystem Inflammatory Disease (NOMID), the most severe form of CAPS.

The Phase 2 trial conducted in Australia, evaluated the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZYIL1 in Subjects with Cryopyrin Associated Periodic Syndromes (CAPS) [ClinicalTrials.gov Identifier: NCT05186051]. ZYIL1 showed rapid oral absorption. ZYIL1 is extremely potent (IC50 in nanomolar range) in human whole blood and supressed inflammation caused by the NLRP3 inflammasome. Robust effect on disease biomarkers including CRP, Serum Amyloid A (SAA), IL-6, WBC, was also observed.

ZYIL1 was safe and well-tolerated and there were no Serious Adverse Events (SAE’s) observed in this Phase 2 trial. Liver and kidney function tests also did not show any abnormalities in this Phase 2 trial. CAPS patients with confirmed NLRP3 mutation suffering from CAPS-related flare up, when treated with ZYIL1 in Phase 2 Proof-of-Concept trial showed rapid clinical improvement as early as day 3 which sustained till the end of treatment.

Lauding the positive proof-of-concept results achieved in CAPS patients as a significant milestone, Mr. Pankaj R. Patel, Chairman, Zydus Lifesciences Ltd. said, “As an innovation driven organization, we have been focussed on making a meaningful difference in the lives of patients. This top-line result from the Phase 2 clinical trial has demonstrated for the first time that ZYIL1, an oral small molecule NLRP3 inhibitor is beneficial in treating chronic inflammation in CAPS patients. Zydus is now planning to conduct further pivotal clinical trials and is committed to develop ZYIL1 for patients living with CAPS and other chronic inflammatory diseases.”

Reference:

1.   ClinicalTrials.gov Identifier: NCT04972188 A Phase I, Prospective, Open Label, Multiple Dose Study of ZYIL1 Administered Via Oral Route to Investigate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics In Healthy Adult Subjects

2.   ClinicalTrials.gov Identifier: NCT04731324 A Phase 1, Prospective Open Label, Single

Dose, Single Arm Study of ZYIL1 Administered Via Oral Route to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Healthy Adult Human Subjects

3.   ClinicalTrials.gov Identifier: NCT05186051 A Phase 2a, Prospective, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZYIL1 in Subjects With Cryopyrin Associated Periodic Syndromes (CAPS)

4.   Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the Oral NLRP3 Inflammasome Inhibitor ZYIL1: First-in-human Phase 1 studies (Single Ascending Dose and Multiple Ascending Dose), Clinical Pharmacology in Drug Development, 2022. DOI: 10.1002/cpdd.1162

About Zydus

The Zydus Group with an overarching purpose of empowering people with freedom to live healthier and more fulfilled lives, is an innovative, global lifesciences company that discovers, develops, manufactures, and markets a broad range of healthcare therapies. The group employs over 23000 people worldwide and is driven by its mission to unlock new possibilities in life- sciences through quality healthcare solutions that impact lives. The group aspires to transform lives through path-breaking discoveries. For more details visit www.zyduslife.com

 

PATENTs

WO2021171230

WO2021111351

WO2021048809, IN202227014064

WO2020148619, EP3911631

WO2019043610, IN202027008328

US2020140382, IN201927046556, WO2018225018

PATENT

https://patentscope.wipo.int/search/en/detail.jsf?docId=US294406517&_cid=P22-L7RNTW-24244-1

Z 1

N-Cyano-N’-[(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl]-4-methylbenzene-1-sulfonimidoamide

 

ACS Medicinal Chemistry Letters (2020), 11(4), 414-418

https://pubs.acs.org/doi/abs/10.1021/acsmedchemlett.9b00433

NLRP3 inflammasome mediated release of interleukin-1β (IL-1β) has been implicated in various diseases. In this study, rationally designed mimics of sulfonylurea moiety were investigated as NLRP3 inhibitors. Our results culminated into discovery of series of unprecedented N-cyano sulfoximineurea derivatives as potent NLRP3 inflammasome inhibitors. Compound 15 (IC50 = 7 nM) and analogs were found to be highly potent and selective NLRP3 inflammasome inhibitor with good pharmacokinetic profile. These effects translate in vivo, as 15, 29, and 34 significantly inhibit NLRP3 dependent IL-1β secretion…

 

N’-cyano-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-methylbenzenesulfonimidamide (15). White solid; mp: 228.5 °C; 1H NMR (400 MHz, DMSO-d6): δ = 7.91 (s, 1H, -NHC=O), 7.65 (d, J = 8.0 Hz, 2H, 2 CH arom), 7.27 (d, J = 8.0 Hz, 2H, 2 CH arom), 6.78 (s, 1H, CH arom), 2.75 – 2.67 (m, 4H, 2 CH2), 2.65 – 2.56 (m, 4H, 2 CH2), 2.34 (s, 3H, C6H4-CH3), 1.92 – 1.83 (m, 4H, 2 CH2); 13C NMR and DEPT (100 MHz, DMSO-d6): δ = 158.1 (C, C=O), 142.7 (C), 142.35 (C), 141.0 (C), 137.7 (C), 132.3 (C), 129.1 (CH), 126.9 (CH), 117.6 (CN), 116.7 (CH), 33.0 (CH2), 30.87 (CH2), 25.5 (CH2), 21.3 (CH3); MS (ESI): m/z (%) = 395.10 (100) (M+H)+ ; ESI-Q-TOF-MS: m/z [M+H]+ calcd for [C21H23N4O2S]+ : 395.1542; found: 395.1578; IR (KBr): ν = 3433(N-H), 3230 (N-H), 2949 (CH3), 2191 (CN), 1599 (C=O),, 1531 (N-H), 1323 (CH2-Ar), 1234 (C-N) cm-1

 

SECOND ONE

PATENT

https://patentscope.wipo.int/search/en/detail.jsf?docId=US294406517&_cid=P22-L7RNTW-24244-1

NLRP3 inflammasome inhibitors reported to be useful for the treatment of cancer, inflammation, neurodegeneration, heteroimmune and autoimmune disease, among others. An exemplified compound (Ex 65 pg 46; EN 1027626) inhibited lipopolysaccharide (LPS)-stimulated IL-1beta production in phorbol 12-myristate 13-acetate (PMA)-differentiated human acute monocytic leukemia THP-1 cells (IC50 = 1.26 nM).

Z 1

N’-Cyano-N-[(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl]-5-(2-hydroxypropan-2-yl)pyridine-3-sulfonimidoamide

N′-cyano-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5-(2-hydroxypropan-2-yl)pyridine-3-sulfonimidamide

       1H NMR (400 MHz, DMSO): δ=8.75-8.72 (m, 2H), 8.22-8.14 (m, 2H), 6.80 (s, 1H), 5.43 (s, 1H), 2.90-2.60 (m, 8H), 1.99-1.76 (m, 4H), 1.48 (s, 3H), 1.47 (s, 3H); MS (ESI): m/z (%)=439.83 (100%) (M+H) +.

/////////

str1
Flag Counter

AS ON DEC2021 3,491,869 VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT

wdt-16

join me on Linkedin

Anthony Melvin Crasto Ph.D – India | LinkedIn

join me on Researchgate

RESEARCHGATE

This image has an empty alt attribute; its file name is research.jpg

join me on Facebook

Anthony Melvin Crasto Dr. | Facebook

join me on twitter

Anthony Melvin Crasto Dr. | twitter

+919321316780 call whatsaapp

EMAIL. amcrasto@amcrasto

/////////////////////////////////////////////////////////////////////////////

old………..

Zydus Cadila gets approval from DCGI for trial of novel molecule ZYIL1

https://www.livemint.com/companies/news/zydus-cadila-gets-approval-from-dcgi-for-trial-of-novel-molecule-zyil1-11607324599234.html

Drug firm Zydus Cadila on Monday said it has received permission from Drugs Controller General of India (DCGI) to initiate phase-1 clinical trial of its novel molecule ZYIL1, indicated for use as an inhibitor for inflammation condition ‘NLRP3’.

In a regulatory filing, Zydus Cadila said “it has received permission to initiate the phase 1 clinical trial of ZYIL1, a novel oral small molecule NLRP3 inhibitor candidate. NLRP3 inflammasomes are involved in the inflammation process”.

This harmful inflammation within the body leads to the onset and development of various kinds of diseases, including Acute Respiratory Distress Syndrome (ARDS), auto-immune diseases, inflammatory diseases, cardiovascular diseases, metabolic disorders, Gastro-intestinal diseases (inflammatory bowel disease), renal diseases and CNS diseases, the company added.

Pankaj R Patel, Chairman, Cadila Healthcare said: “We will study the safety, tolerability, pharmacokinetics and pharmacodynamics of ZYIL1 in this phase I clinical trial in healthy human volunteers. We are committed to developing these pioneering novel treatments to the clinic for the patients in need.”

////////////ZYIL 1, PHASE 2, ZYDUS

It's only fair to share...Flattr the authorPin on PinterestEmail this to someone
Buffer this pageDigg thisShare on FacebookShare on Google+Tweet about this on TwitterShare on LinkedInShare on YummlyShare on VKShare on RedditShare on StumbleUponPrint this pageShare on Tumblr

Leave a Reply

Your email address will not be published. Required fields are marked *