Florensocatib

 

Florensocatib

CAS 2762114-61-2

MF C23H23FN4O4 MW438.5 g/mol

(2S)-N-[(1S)-1-cyano-2-[2-fluoro-4-(3-methyl-2-oxo-1,3-benzoxazol-5-yl)phenyl]ethyl]-1,4-oxazepane-2-carboxamide

(2S)-N-{(1S)-1-cyano-2-[2-fluoro-4-(3-methyl-2-oxo-2,3-dihydro1,3-benzoxazol-5-yl)phenyl]ethyl}-1,4-oxazepane-2-
carboxamide
cathepsin inhibitor, HSK 31858, CHF 10196, DPP1-IN-1, RWC743JRK7

Florensocatib (originally designated as HSK31858 or CHF10196) is an investigative, highly potent, oral reversible inhibitor of dipeptidyl peptidase 1 (DPP1). It is being actively researched for its ability to reduce the frequency of pulmonary exacerbations in adults suffering from inflammatory respiratory diseases like bronchiectasis

Mechanism of Action

DPP1 (also known as cathepsin C) is a lysosomal protease enzyme responsible for activating neutrophil serine proteases (NSPs). In conditions like non-cystic fibrosis bronchiectasis, hyperactive neutrophils accumulate in the airways, causing severe tissue damage, chronic inflammation, and airway widening.

By inhibiting DPP1, florensocatib prevents the activation of these damaging enzymes, effectively targeting the primary driver of neutrophilic inflammation in the lungs.

Clinical Development & Trial Progress

Florensocatib is undergoing global evaluation across multiple advanced clinical trials:

• The SAVE-BE Trial: An earlier clinical phase where the drug demonstrated high potency and favorable efficacy profiles in treating inflammatory lung conditions.
• The HOPE-BE Trial: A definitive Phase III protocol launched to evaluate the long-term safety and overall reduction of pulmonary exacerbation frequencies specifically among Chinese adults.
• Global Phase III Status: According to records on ClinicalTrials.gov, randomised, double-blind trials are evaluating the drug against a placebo in participants aged 12 to 85 for treatment windows stretching up to 78 weeks.

SYN

US11807635,

https://patentscope.wipo.int/search/en/detail.jsf?docId=US395653715&_cid=P21-MPKKTA-33002-1

Example 1: (S)—N—((S)-1-cyano-2-(2-fluoro-4-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)phenyl)ethyl)-1,4-oxazepane-2-carboxamide (Compound 1)

Step 4: (S)—N—((S)-1-cyano-2-(2-fluoro-4-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)phenyl)ethyl)-1,4-oxazepane-2-carboxamide (Compound 1)

1D (0.32 g, 0.59 mmol) was dissolved in formic acid (2.5 mL) and upon completion of the addition, the mixture was reacted at 50° C. for 10 min. The reaction solution was concentrated to dryness and ethyl acetate (20 mL) was added. Then saturated aqueous sodium bicarbonate solution was added dropwise to adjust the pH to about 8. The organic layer was separated and the remaining aqueous layer was extracted with ethyl acetate (25 mL×3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered and concentrated, and the residue was separated and purified by silica gel column chromatography (dichloromethane:methanol (v/v)=20:1) to obtain the title compound 1 (0.15 g, 58.0%). LC-MS (ESI): m/z=439.1 [M+H] +.

1H NMR (400 MHz, CDCl 3) δ 7.43-7.22 (m, 5H), 7.12 (d, 1H), 5.19 (dd, 1H), 4.18-4.04 (m, 1H), 4.05-3.95 (m, 1H), 3.78 (m, 1H), 3.46 (s, 3H), 3.41-3.17 (m, 3H), 3.03-2.87 (m, 3H), 1.88 (m, 2H).

SYN

US11807635,

https://patentscope.wipo.int/search/en/detail.jsf?docId=US395653715&_cid=P21-MPKKYT-35548-1

PAT

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2022042591&_cid=P21-MPKKS9-32509-1

(S)-N-((S)-1-cyano-2-(2-fluoro-4-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)phenyl)ethyl)-1,4-oxazepane-2-carboxamide(compound 1)

Step 4: (S)-N-((S)-1-cyano-2-(2-fluoro-4-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)phenyl)ethyl)-1,4-oxazacycloheptane-2-carboxamide (Compound 1) 

[0360]

(S)-N-((S)-1-cyano-2-(2-fluoro-4-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)phenyl)ethyl)-1,4-oxazepane-2-carboxamide(compound 1)

[0361]1D (0.32 g, 0.59 mmol) was dissolved in formic acid (2.5 mL), and the mixture was reacted at 50 °C for 10 min after the addition was complete. The solution was concentrated to dryness, and ethyl acetate (20 mL) was added. The pH was adjusted to approximately 8 by dropwise addition of saturated sodium bicarbonate solution. The organic layer was separated and extracted with ethyl acetate (25 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated, and the residue was purified by silica gel column chromatography (dichloromethane:methanol (v/v) = 20:1) to give title compound 1 (0.15 g, 58.0%). LC-MS (ESI): m/z = 439.1 [M+H] ⁺ . 

[0362]

¹H NMR(400MHz,CDCl ₃)δ7.43–7.22(m,5H),7.12(d,1H),5.19(dd,1H),4.18–4.04(m,1H),4.05–3.95(m,1H),3.78(m,1H),3.46(s,3H),3.41–3.17(m,3H),3.03–2.87(m,3H),1.88(m,2H).

ADVT

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References

• Nitrile derivative that acts as inhibitor of dipeptidyl peptidase 1 and use thereofPublication Number: US-2023121807-A1Priority Date: 2020-08-26
• Nitrile derivative that acts as inhibitor of dipeptidyl peptidase 1 and use thereofPublication Number: WO-2022042591-A1Priority Date: 2020-08-26
• Nitrile derivative as dipeptidyl peptidase 1 inhibitor and application thereofPublication Number: CN-115996923-APriority Date: 2020-08-26
• Nitrile derivative that acts as inhibitor of dipeptidyl peptidase 1 and use thereofPublication Number: EP-4129989-A1Priority Date: 2020-08-26
• Dipeptidyl peptidase 1 inhibitor polymorph and preparation method and application thereofPublication Number: CN-118696040-APriority Date: 2022-02-22
• Salt and crystal form of dipeptidyl peptidase inhibitor compoundPublication Number: EP-4484414-A1Priority Date: 2022-02-22
• Nitrile derivative that acts as inhibitor of dipeptidyl peptidase 1 and use thereofPublication Number: US-11807635-B2Priority Date: 2020-08-26Grant Date: 2023-11-07
• A kind of nitrile derivative as dipeptidyl peptidase 1 inhibitor and use thereofPublication Number: TW-202214616-APriority Date: 2020-08-26
• Nitrile derivatives acting as inhibitors of dipeptidyl peptidase 1 and uses thereofPublication Number: KR-20230084134-APriority Date: 2020-08-26
• Salt and crystal form of dipeptidyl peptidase inhibitor compoundPublication Number: WO-2023160542-A1Priority Date: 2022-02-22
• Dipeptidyl peptidase 1 inhibitor polymorph, preparation method and use thereforPublication Number: WO-2023160579-A1Priority Date: 2022-02-22
• Salts and crystalline forms of dipeptidyl peptidase inhibitor compoundsPublication Number: CN-118660873-APriority Date: 2022-02-22
• Preparation method of nitrogen-containing heterocyclic compoundPublication Number: WO-2023160541-A1Priority Date: 2022-02-22
• Preparation method of nitrogen-containing heterocyclic compoundPublication Number: CN-118742547-APriority Date: 2022-02-22
• Dipeptidyl peptidase 1 inhibitors and uses thereofPublication Number: WO-2025059526-A1Priority Date: 2023-09-15
• Pharmaceutical composition containing dipeptidyl peptidase small molecule inhibitorPublication Number: WO-2024193695-A1Priority Date: 2023-03-23
• Uses of certain 1,4-oxazepane-2-carboxamides as dpp1 inhibitorsPublication Number: WO-2024173556-A2Priority Date: 2023-02-15
• Novel dpp1 inhibitors and uses thereofPublication Number: WO-2024026433-A2Priority Date: 2022-07-28
• Novel dpp1 inhibitors and uses thereofPublication Number: EP-4561565-A2Priority Date: 2022-07-28

/////////florensocatib, anax labs, cathepsin inhibitor, HSK 31858, CHF 10196, DPP1-IN-1, RWC743JRK7

#florensocatib, #anax labs, #cathepsin inhibitor, #HSK 31858, #CHF 10196, #DPP1-IN-1, #RWC743JRK7

Flormotridazum (18F)

 

Flormotridazum (18F)

CAS 2798832-03-6

MF C23H29Cl18FN5O4 MW492.961

2-tert-butyl-4-chloro-5-[(3-{[4-({2-[2-(18F)fluoroethoxy]ethoxy}methyl)-1H-1,2,3-triazol-1-yl]methyl}phenyl)methoxy]pyridazin-3(2H)-one

3(2H)-Pyridazinone, 4-chloro-2-(1,1-dimethylethyl)-5-[[3-[[4-[[2-[2-(fluoro-18F)ethoxy]ethoxy]methyl]-1H-1,2,3-triazol-1-yl]methyl]phenyl]methoxy]-

2-tert-butyl-4-chloro-5-[(3-{[4-({2-[2-(18F)fluoroethoxy]ethoxy}methyl)-1H-1,2,3-triazol-1-yl]methyl}phenyl)methoxy]pyridazin-3(2H)-one

imaging agent, 7AR6ZH8YUU

Flormotridaz (18F) (also referred to by its International Nonproprietary Name, flormotridazum) is an advanced radiopharmaceutical compound utilized in nuclear medicine. It is specifically engineered as a radioactive diagnostic tracer containing the fluorine-18 positron-emitting isotope.

Core Characteristics & Chemical Profile

• Substance Classification: Radioactive Diagnostic Agent / Small Molecule.
• Mechanism Basis: It shares core structural similarities and structural lineage with pyridazinone-based mitochondrial complex 1 (MC-1) inhibitors, heavily linking its functionality to target-specific tissues with high metabolic or mitochondrial activity.

Mechanism and Clinical Application

Like related fluorine-18 labeled pyridazinone analogues, this agent is designed for Positron Emission Tomography (PET) imaging workflows. [1]

1. Administration: The agent is administered intravenously as a sterile unit dose before scanning.
2. Cellular Targeting: It binds selectively to specific intracellular molecular targets (such as mitochondrial pathways) within highly active tissues.
3. PET Imaging: As the Fluorine-18 radioisotope decays, it emits positrons. These positrons encounter electrons to produce gamma rays, which the PET scanner captures to map high-resolution, three-dimensional metabolic layouts of internal organ systems.

Contextual Comparison

In clinical nuclear medicine, molecular tracers tagged with Fluorine-18 offer significant clinical benefits over older Single-Photon Emission Computed Tomography (SPECT) agents. Their 110-minute half-life allows them to be manufactured at centralized cyclotron facilities and distributed directly to regional medical centres as ready-to-use unit doses, eliminating the need for an on-site cyclotron

Flormotridaz (\(^{18}\text{F}\)):

1. CN112807276B: "Preparation method and application of a pyridazinone myocardial perfusion PET radiopharmaceutical" (Covers the definitive radiosynthesis scheme).
2. CN115947775A: "Method for preparing compound (I), compound (I), and uses thereof".
3. WO2024008073A1 / CN114832118B: "Compound I liquid composition, preparation method and use thereof" (Covers final formulation stabilization utilizing vitamin C and gentisic acid)

PAT

https://patents.google.com/patent/WO2024008073A1/zh

Compound I, chemically named 2-tert-butyl-4-chloro-5-((3-((4-((2-(2-fluoro[ ^18F ]ethoxy)ethoxy)methyl)-1H-1,2,3-triazol-1-yl)methyl)benzyl)oxy)pyridazine-3(2H)-one. Chemical structural formula:_Molecular formula : _{C₂₃H₂₉Cl₁₈FN₅O₄}​

_​Molecular weight: 492.97The mechanism of action of compound I as a myocardial perfusion PET imaging agent: Once compound I enters cardiomyocytes, it can rapidly interact with respiratory chain complex I (MC-I) in mitochondria and remain in the myocardium for a long time. Preliminary animal studies showed that it has high cardiac uptake and low hepatic uptake 15 minutes after injection, and maintains a good heart-liver ratio 60 minutes after injection, showing good potential for myocardial perfusion imaging.In this application, Compound I liquid composition or Compound I is used as a myocardial perfusion PET imaging agent.Precursor of Compound I: Chemical name is methyl 2-(2-((1-(3-(((1-(tert-butyl)-5-chloro-6-oxo-1,6-dihydropyridazin-4-yl)oxy)methyl)benzyl)-1H-1,2,3-triazol-4-yl)methoxy)ethoxy)ethyl-4-methylbenzenesulfonate, chemical structural formula is:_Molecular formula : _{C30H36ClN5O7S}

_​Molecular weight: 646.16Amino polyethers (K222 ₎ are tribridged crown ether molecules with cavitary structures, and are typical nitrogen-containing cavitary ethers, belonging to the category of cavitary ethers. Due to their unique coordination properties, nitrogen-containing cavitary ethers can effectively and selectively complex transition metal and heavy metal cations, forming more stable complexes. Furthermore, they possess both lipophilic and hydrophilic properties, thus showing promising research potential.In existing technologies, the classic synthetic method for amino polyether (K 

_​​222 ) is the highly diluted method proposed by Lehn et al., which is a typical non-template ion synthesis method. The specific steps involve dissolving the starting materials 1,8-diamino-3,6-dioxane and 1,8-diacyl chloride-3,6-dioxane in a large amount of benzene solvent and heating the reaction for 8 hours. Then, a reduction reaction with lithium aluminum hydride is performed for 24 hours, followed by column chromatography separation and recrystallization to obtain amino polyether (K 

_​​222 ). This method requires a large amount of solvent, such as benzene, has a long synthetic route, is complex, has a low yield, and is not economically efficient. Besides the highly diluted method, another classic synthetic method for amino polyether (K_​​222 ) is proposed by Kulstad and Malmsten, which uses Na 2CO ₃ 

_{as a template to obtain a sodium iodide complex of amino polyether (K ​​222} ) in acetonitrile , and then decomplexes it using a resin to obtain amino polyether (K _​​222 ). The specific steps are as follows: 1,2-bis(2-iodoethoxy)ethane and benzylamine are refluxed in acetonitrile solution for 3 days. An intermediate is then obtained through post-processing. This intermediate is recrystallized from acetone and filtered to obtain a NaI complex. This complex is then decomplexed under acidic conditions using cation exchange resins and anion exchange resins to prepare amino polyether (K222 ₎ . This method uses simple equipment, requires little solvent, and has relatively mild reaction conditions. However, the applicant has found that the decomplexing method using ion exchange resins fails to proceed when the sodium ion content decreases to a certain level, resulting in a low yield.

PAT

https://patents.google.com/patent/CN114773179B/en

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References

//////////flormotridazum (18F), anax labs, imaging agent, 7AR6ZH8YUU

#flormotridazum (18F), #anax labs, #imaging agent, #7AR6ZH8YUU

Bulevirtide-gmod

 

Bulevirtide-gmod

CAS 2012558-47-1.

MF C₂₄₈H₃₅₅N₆₅O₇₂ MW 5399 g/mol

FDA 2026, APPROVALS 2026, 5/22/2026, Hepcludex, WKM56H3TLB

To treat chronic hepatitis delta virus infection in adults without cirrhosis or with compensated cirrhosis

N-myristoyl-glycyl-L-threonyl-L-asparagyl-L-leucyl-L-seryl-L-valyl-L-prolyl-L-asparagyl-L-prolyl-L-leucyl-glycyl-L-phenylalanyl-L-phenylalanyl-L-prolyl-L-alpha-aspartyl-L-histidyl-L-glutaminyl-L-leucyl-L-alpha-aspartyl-L-prolyl-L-alanyl-L-phenylalanyl-glycyl-L-alanyl-L-asparagyl-L-seryl-L-asparagyl-L-asparagyl-L-prolyl-L-alpha-aspartyl-L-tryptophyl-L-alpha-aspartyl-L-phenylalanyl-L-asparagyl-L-prolyl-L-asparagyl-L-lysyl-L-alpha-aspartyl-L-histidyl-L-tryptophyl-L-prolyl-L-alpha-glutamyl-L-alanyl-L-asparagyl-L-lysyl-L-valyl-glycinamide

(4S)-4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-4-amino-2-[[(2S)-1-[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-4-amino-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-1-[(2S)-4-amino-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S,3R)-3-hydroxy-2-[[2-(tetradecanoylamino)acetyl]amino]butanoyl]amino]-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]-3-methylbutanoyl]pyrrolidine-2-carbonyl]amino]-4-oxobutanoyl]pyrrolidine-2-carbonyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-phenylpropanoyl]pyrrolidine-2-carbonyl]amino]-3-carboxypropanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-3-carboxypropanoyl]pyrrolidine-2-carbonyl]amino]propanoyl]amino]-3-phenylpropanoyl]amino]acetyl]amino]propanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxypropanoyl]amino]-4-oxobutanoyl]amino]-4-oxobutanoyl]pyrrolidine-2-carbonyl]amino]-3-carboxypropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-carboxypropanoyl]amino]-3-phenylpropanoyl]amino]-4-oxobutanoyl]pyrrolidine-2-carbonyl]amino]-4-oxobutanoyl]amino]hexanoyl]amino]-3-carboxypropanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-5-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[(2-amino-2-oxoethyl)amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-oxopentanoic acid

Bulevirtide-gmod, sold under the brand name Hepcludex, is the first and only FDA-approved medication for treating chronic hepatitis delta virus (HDV) infection in adults. Developed by Gilead Sciences, it received accelerated approval from the U.S. Food and Drug Administration (FDA) on May 22, 2026, filling a critical gap for patients with this severe viral liver disease.

Indication and Clinical Use

• Target Patient Profile: Approved for adults with chronic HDV who have compensated cirrhosis or no cirrhosis.
• The Clinical Need: HDV only occurs as a co-infection in individuals who already have Hepatitis B (HBV). It is considered the most aggressive form of viral hepatitis, often accelerating liver scarring (fibrosis), liver failure, and liver cancer.
• Basis of Approval: The FDA granted accelerated approval based on Phase 3 MYR301 study data, which demonstrated a significant reduction in viral HDV RNA and the normalization of alanine aminotransferase (ALT) liver enzymes.

Mechanism of Action

Bulevirtide-gmod is a first-in-class entry inhibitor. It works by binding to and blocking the sodium taurocholate co-transporting polypeptide (NTCP) receptor on liver cells. Because HDV and HBV rely on this specific receptor to enter hepatocytes, the drug successfully disrupts the viral life cycle and prevents the virus from spreading to healthy liver cells.

Dosage and Administration

• Form: Supplied as a lyophilized powder for injection.
• Dose: The recommended dose is 8.5 mg once daily.
• Administration: Delivered via subcutaneous injection (under the skin).

Safety and Side Effects

• Boxed Warning: The drug carries a prominent warning regarding the risk of severe acute exacerbations of hepatitis D and B if treatment is discontinued. Stopping the medication can cause severe, life-threatening viral flares, requiring close medical monitoring for at least 6 months post-treatment.
• Common Side Effects: The most frequent adverse reactions of patients) include:
  • Injection site reactions
  • Headache
  • Abdominal pain
  • Fatigue
  • Pruritus (itching)

Bulevirtide, sold under the brand name Hepcludex, is an antiviral medication used for the treatment of chronic hepatitis D (in the presence of hepatitis B).^[8]

The most common side effects include raised levels of bile salts in the blood and reactions at the site of injection.^[8]

Bulevirtide works by attaching to and blocking a receptor (target) through which the hepatitis delta and hepatitis B viruses enter liver cells.^[8] By blocking the entry of the virus into the cells, it limits the ability of HDV to replicate and its effects in the body, reducing symptoms of the disease.^[8]

Bulevirtide was approved for medical use in the European Union in July 2020,^[8] and in Canada in August 2025.^[5]

Medical uses

Bulevirtide is indicated for the treatment of chronic hepatitis delta virus (HDV) infection in plasma (or serum) HDV-RNA positive adult patients with compensated liver disease.^[8][10]

Pharmacology

Mechanism of action

Bulevirtide binds and inactivates the sodium/bile acid cotransporter, blocking both hepatitis B and hepatitis D viruses from entering hepatocytes.^[11]

The hepatitis B virus uses its surface lipopeptide pre-S1 for docking to mature liver cells via their sodium/bile acid cotransporter (NTCP) and subsequently entering the cells. Myrcludex B is a synthetic N-acylated pre-S1^[12][13] that can also dock to NTCP, blocking the virus's entry mechanism.^[14]

Bulevirtide is also effective against hepatitis D because the hepatitis D virus uses the same entry receptor as the hepatitis B virus and is only effective in the presence of a hepatitis B virus infection.^[14]

Pre-clinical data in mice suggests that pharmacological inhibition of NTCP-mediated bile salt uptake may also be effective to lower hepatic bile salt accumulation in cholestatic conditions. This reduces hepatocellular damage.^[15] An increased ratio of phospholipid to bile salts seen in bile upon NTCP inhibition may further contribute to the protective effect as bile salts are less toxic in presence of phospholipids.^[16]

Structural formula

Bulevirtide is a 47-amino acid peptide with the following sequence:^[17]

CH₃(CH₂)₁₂CO-Gly-Thr-Asn-Leu-Ser-Val-Pro-Asn-Pro-Leu-Gly-Phe-Phe-Pro-Asp-His-Gln-Leu-Asp-Pro-Ala-Phe-Gly-Ala-Asn-Ser-Asn-Asn-Pro-Asp-Trp-Asp-Phe-Asn-Pro-Asn-Lys-Asp-His-Trp-Pro-Glu-Ala-Asn-Lys-Val-Gly-NH₂ (C₁₃H₂₇CO-GTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPNKDHWPEANKVG-NH₂)

SYN

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2024073572&_cid=P11-MPNG4J-82875-1

PATENTS

• Therapy of atherosclerosis, primary biliary cirrhosis and nrlp3 inflammasome-associated disease by htcp inhibitorsPublication Number: EP-3392267-A1Priority Date: 2017-04-18
• Therapy of atherosclerosis, primary biliary cirrhosis and nrlp3 inflammasome-associated disease by htcp inhibitorsPublication Number: US-2018296634-A1Priority Date: 2017-04-18
• Therapy of atherosclerosis, primary biliary cirrhosis and nrlp3 inflammasome-associated disease by htcp inhibitorsPublication Number: US-2021196786-A1Priority Date: 2017-04-18
• Therapy of atherosclerosis, primary biliary cirrhosis and NRLP3 inflammasome-associated disease by HTCP inhibitorsPublication Number: US-10925925-B2Priority Date: 2017-04-18Grant Date: 2021-02-23
• Combination therapy of hbv and hdv infectionPublication Number: EP-3204030-B1Priority Date: 2014-10-07Grant Date: 2022-04-27
• Combination therapy of hbv and hdv infectionPublication Number: EP-4098273-A1Priority Date: 2014-10-07
• Combination therapy of hbv and hdv infectionPublication Number: US-2022040178-A1Priority Date: 2014-10-07

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References

References

1.  Deterding K, Wedemeyer H (2019). "Beyond Pegylated Interferon-Alpha: New Treatments for Hepatitis Delta". AIDS Reviews. 21 (3): 126–134. doi:10.24875/AIDSRev.19000080. PMID 31532397. S2CID 202674681.
2.  "Hepcludex (bulevirtide acetate)". Therapeutic Goods Administration (TGA). 12 August 2024. Retrieved 12 October 2024.
3.  "Therapeutic Goods (Poisons Standard—June 2024) Instrument 2024". Federal Register of Legislation. 30 May 2024. Retrieved 10 June 2024.
4.  "Hepcludex (Gilead Sciences Pty Ltd)". Therapeutic Goods Administration (TGA). 13 September 2024. Retrieved 15 September 2024.
5.  "Hepcludex Product information". Health Canada. 8 August 2025. Retrieved 20 August 2025.
6.  "Summary Basis of Decision for Hepcludex". Drug and Health Products Portal. 29 September 2025. Retrieved 12 October 2025.
7.  "Hepcludex 2 mg powder for solution for injection - Summary of Product Characteristics (SmPC)". (emc). 30 March 2022. Retrieved 1 July 2022.
8.  "Hepcludex EPAR". European Medicines Agency (EMA). 26 May 2020. Retrieved 12 August 2020. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
9.  "Hepcludex Product information". Union Register of medicinal products. Retrieved 3 March 2023.
10.  "Summary of opinion: Hepcludex" (PDF). European Medicines Agency (EMA). 28 May 2020.
11.  Francisco EM (29 May 2020). "Hepcludex". European Medicines Agency (EMA). Archived from the original on 15 June 2020. Retrieved 6 August 2020.
12.  Volz T, Allweiss L, Ben MBarek M, Warlich M, Lohse AW, Pollok JM, et al. (May 2013). "The entry inhibitor Myrcludex-B efficiently blocks intrahepatic virus spreading in humanized mice previously infected with hepatitis B virus". Journal of Hepatology. 58 (5): 861–867. doi:10.1016/j.jhep.2012.12.008. PMID 23246506.
13.  Abbas Z, Abbas M (August 2015). "Management of hepatitis delta: Need for novel therapeutic options". World Journal of Gastroenterology. 21 (32): 9461–9465. doi:10.3748/wjg.v21.i32.9461. PMC 4548107. PMID 26327754.
14.  Spreitzer H (14 September 2015). "Neue Wirkstoffe – Myrcludex B". Österreichische Apothekerzeitung (in German) (19/2015): 12.
15.  Na+ -taurocholate cotransporting polypeptide inhibition has hepatoprotective effects in cholestasis in mice. Slijepcevic D, Roscam Abbing RLP, Fuchs CD, Haazen LCM, Beuers U, Trauner M, Oude Elferink RPJ, van de Graaf SFJ. Hepatology. 2018 Sep;68(3):1057-1069. doi: 10.1002/hep.29888
16.  Roscam Abbing RL, Slijepcevic D, Donkers JM, Havinga R, Duijst S, Paulusma CC, et al. (January 2020). "Blocking Sodium-Taurocholate Cotransporting Polypeptide Stimulates Biliary Cholesterol and Phospholipid Secretion in Mice". Hepatology. 71 (1): 247–258. doi:10.1002/hep.30792. PMC 7003915. PMID 31136002.
17.  Sauter M, Blank A, Stoll F, Lutz N, Haefeli WE, Burhenne J (September 2021). "Intact plasma quantification of the large therapeutic lipopeptide bulevirtide". Analytical and Bioanalytical Chemistry. 413 (22): 5645–5654. doi:10.1007/s00216-021-03384-7. PMC 8410713. PMID 34018034.

Clinical data
Pronunciation	/bjuːˈlɛvɪrtaɪd/ byoo-LEH-vir-tyde
Trade names	Hepcludex
Other names	MyrB, Myrcludex-B[1]
License data	US DailyMed: Bulevirtide
Pregnancy category	AU: B1[2]
Routes of administration	Subcutaneous
ATC code	J05AX28 (WHO)
Legal status
Legal status	AU: S4 (Prescription only)[3][4][2]CA: ℞-only[5][6]UK: POM (Prescription only)[7]EU: Rx-only[8][9]
Identifiers
CAS Number	2012558-47-1
DrugBank	DB15248
ChemSpider	129157549
UNII	WKM56H3TLB
KEGG	D11877as salt: D11878
ChEMBL	ChEMBL4297711
Chemical and physical data
Formula	C248H355N65O72
Molar mass	5398.951 g·mol−1
3D model (JSmol)	Interactive image
SMILES
InChI

/////////Bulevirtide-gmod, ANAX LABS, FDA 2026, APPROVALS 2026, Hepcludex, WKM56H3TLB, ANTIVIRALS

#Bulevirtide-gmod, #ANAX LABS, #FDA 2026, #APPROVALS 2026, #Hepcludex, #WKM56H3TLB, #ANTIVIRALS

Fosizensertib

 

Fosizensertib

CAS 2905377-00-4

MF C22H21F2N4O5P MW490.4 g/mol

[(2S)-1-[[5-[2-[1-(difluoromethyl)pyrazol-4-yl]ethynyl]pyridine-3-carbonyl]-methylamino]-3-phenylpropan-2-yl] dihydrogen phosphate

(2S)-1-(5-{[1-(difluoromethyl)-1H-pyrazol-4-yl]ethynyl}-Nmethylpyridine-3-carboxamido)-3-phenylpropan-2-yl dihydrogen
phosphate
receptor-interacting serine/threonine protein (RIP-1) kinase inhibitor, ABBV-668, ABBV 668, 6GA6XSX5SL

Fosizensertib (also known by the developmental code ABBV-668) is an investigational small molecule drug being evaluated for the treatment of ulcerative colitis and other chronic autoimmune or inflammatory conditions.

Mechanism of Action

• Target: It acts as a selective inhibitor of receptor-interacting serine/threonine-protein kinase 1 (RIPK1), an enzyme that plays a critical role in regulating cellular inflammation and necroptosis (programmed cell death).
• Prodrug Design: Fosizensertib functions as a phosphate prodrug. When administered, it is essentially inactive in vitro (inhibiting RIPK1 by less than 10%).
• Bioactivation: Once inside the body, it undergoes in vivo dephosphorylation to convert into its active metabolite (Compound 2), which strongly inhibits RIPK1 activity to suppress inflammatory pathways.

According to resources like the IUPHAR/BPS Guide to Pharmacology and PubChem, its core chemical metrics include:

Fosizensertib was assigned its International Nonproprietary Name (INN) by the World Health Organization (WHO). Developed by the pharmaceutical company AbbVie, it is classified as a clinical candidate intended for oral administration. It is currently restricted strictly to laboratory research and clinical evaluation settings and is not approved for general prescription or veterinary use.

PAT

[WO2023018643A1]

https://patentscope.wipo.int/search/en/detail.jsf;jsessionid=66762EE22EF5E77E0FC927179EB58712.wapp2nB?docId=WO2023018643&_cid=P21-MPOVCH-38336-1

(S)-1-(5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)-N-methylnicotinamido)-3-phenylpropan-2-yl dihydrogen phosphate;

Examples #18 and 19: (S)–di–tert–butyl (1–(5–((1–(difluoromethyl)–1H–pyrazol–4– yl)ethynyl)–N–methylnicotinamido)–3–phenylpropan–2–yl) phosphate (Example #18) and (S)–1–(5–((1–(difluoromethyl)–1H–pyrazol–4–yl)ethynyl)–N–methylnicotinamido)–3– phenylpropan–2–yl dihydrogen phosphate (Example #19)

[0173] To a solution of (S)-5-((1-(difluoromethyl)-1H-pyrazol-4-yl)ethynyl)-N-(2-hydroxy- 3-phenylpropyl)-N-methylnicotinamide (Example #2) (500 mg, 1.22 mmol) in N-Methyl-2- pyrrolidinone (1000 mL) was added di-tert-butyl diethylphosphoramidite (304 mg, 1.22 mmol) and 1H-tetrazole (10.8 mL, 4.87 mmol) in one portion at 20 °C under N₂. The mixture was stirred at 40 °C for 3 hours. Hydrogen peroxide (5.0 mL, 49 mmol) was added to the solution at 0 °C, and the mixture was stirred for an additional 2 hours. The mixture was poured into saturated Na2SO₃ (75 mL) and extracted with ethyl acetate (EtOAc) (3 × 100 mL). The organic phase was washed with brine (100 mL), dried over Na₂SO₄, concentrated under reduced pressure to give the crude t-butyl phosphate ester, which was chromatographed on silica gel (petroleum ether: ethyl acetate=1:1-1:4) to provide (S)-di-tert-butyl (1-(5-((1-(difluoromethyl)-1H-pyrazol-4- yl)ethynyl)-N-methylnicotinamido)-3-phenylpropan-2-yl) phosphate (Example #18) (384 mg, 0.64 mmol, 52% yield). LC/MS (Table B, Method aa) R_t = 1,73 min; MS m/z: 545.20 (M-tBu)⁺; ¹H NMR (400 MHz, DMSO-d₆) δ 8.76 – 8.40 (m, 3H), 8.15 – 7.60 (m, 3H), 7.27-7.01 (m, 5H), 4.78-4.46 (br m, 1H), 3.75-2.72 (m, 7H), 1.50-1.18 (m, 18H). tBu = tert–butyl; Et = ethyl.

[0174] A flask was charged with (S)-di-tert-butyl (1-(5-((1-(difluoromethyl)-1H-pyrazol-4- yl)ethynyl)-N-methylnicotinamido)-3-phenylpropan-2-yl) phosphate (Example #18) (381 mg, .632 mmol), dichloromethane (DCM) (5 mL) and trifluoroacetic acid (TFA) (0.61 mL, 7.9 mmol) and stirred at room temperature for approximately 19 hours. The mixture was concentrated under reduced pressure, then purified via reverse phase liquid chromatography (Atlantis^® Prep T3 Phenomenex 5 μm 19 x 50 mm column, 5 to 95 acetonitrile (MeCN):water (formic acid buffer) at 1 mL/minute) to provide the title compound, Example #19 (230 mg, 0.47 mmol, 74% yield). LC/MS (Table B, Method ff) R_t = 1.96 min; MS m/z: 491.0 (M+H)⁺; ¹H NMR (400 MHz,

DMSO-d₆) δ 8.78 – 8.69 (m, 1H), 8.65 – 8.57 (m, 1H), 8.44 (d, J = 1.0 Hz, 1H), 8.14 – 8.08 (m, 1H), 8.03 – 7.99 (m, 1H), 7.97 (s, 1H), 7.88 – 7.84 (m, 1H), 7.76 (s, 1H), 7.73 – 7.69 (m, 1H), 7.35 – 7.28 (m, 2H), 7.27 – 7.21 (m, 1H), 7.19 – 7.12 (m, 1H), 7.03 (br d, J = 7.5 Hz, 1H), 4.80 – 4.73 (m, 1H), 4.52 – 4.45 (m, 1H), 3.84 – 3.76 (m, 1H), 3.66 (br d, J = 13.5 Hz, 1H), 3.33 (br dd, J = 9.5, 13.5 Hz, 1H), 3.27 – 3.11 (m, 1H), 3.08 – 3.00 (m, 1H), 2.97 (s, 1H), 2.95 (br s, 1H), 2.92 (s, 2H), 2.90 - 2.85 (m, 1H), 2.79 - 2.69 (m, 1H), 2.07 (s, 1H), 1.78 (s, 1H), 1.74 (s, 1H).

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References

• Nicotinamide ripk1 inhibitorsPublication Number: WO-2023018643-A1Priority Date: 2021-08-10
• Nicotinamide ripk1 inhibitorsPublication Number: EP-4301744-A1Priority Date: 2021-08-10
• Nicotinamide RIPK1 inhibitorsPublication Number: US-11767310-B2Priority Date: 2021-08-10Grant Date: 2023-09-26
• Nicotinamide ripk1 inhibitorsPublication Number: US-2023127127-A1Priority Date: 2021-08-10

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#fosizensertib, #anax labs, #ABBV-668, #ABBV 668, #6GA6XSX5SL