Multicentric phase I (dose escalation plus expansion) clinical trial of PBF-999 in patients with immunotherapy naïve and pretreated solid tumors to evaluate the safety, tolerability and preliminary efficacy of the compound

开始日期2017-10-01

申办/合作机构

Palobiofarma SL

[+1]

NCT02907294 / Terminated临床1期

Randomized, Double Blind, Placebo Controlled, Parallel Groups Study to Assess the Safety, Tolerability and Pharmacokinetic Profile of PBF-999 (160 mg and 320 mg) "After Multiple Oral Doses" in Healthy Volunteers

To assess the safety and tolerability of five doses of PBF-999 (160 mg and 320mg) after repeated (8 days) single daily oral dose administration in young male and female healthy subjects.

开始日期2016-03-01

申办/合作机构

Palobiofarma SL

100 项与 PBF-999 相关的临床结果

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100 项与 PBF-999 相关的转化医学

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100 项与 PBF-999 相关的专利（医药）

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项与 PBF-999 相关的文献（医药）

2023-10-07·Molecules (Basel, Switzerland)

Synthesis, Crystal Structure, Spectral Characterization and Antifungal Activity of Novel Phenolic Acid Triazole Derivatives.

Article

作者: Peng, Da-Yong ; Xiong, Xin-Ting ; Song, Xiu-Ying ; Xiao, Pan-Lei ; Nie, Xu-Liang

At present, phenolic acid derivatives and triazole derivatives have a good antifungal effect, which has attracted widespread attention. A series of novel phenolic acid triazole derivatives were synthesized, and their structures were characterized by IR, MS, NMR, and X-ray crystal diffraction. Compound methyl 4-(2-bromoethoxy)benzoate, methyl 4-(2-(1H-1,2,4-triazol-1-yl) ethoxy)benzoate, 4-(2-(1H-1,2,4-triazol-1-yl)ethoxy)benzoic acid and 4-(2-(1H-1,2,4-triazol-1-yl) ethoxy)-3-methoxybenzoic acid crystallize in the monoclinic system with space group P2₁/n, the monoclinic system with space group P2₁, the monoclinic system with space group P2₁ and the orthorhombic system with space group Pca2₁, respectively. At a concentration of 100 μg/mL and 200 μg/mL, the antifungal activity against seven plant pathogen fungi was determined. Compound methyl 4-(2-bromoethoxy)benzoate has the best inhibitory effect on Rhizoctonia solani AG1, and the inhibitory rate reached 88.6% at 200 μg/mL. The inhibitory rates of compound methyl 4-(2-(1H-1,2,4-triazol-1-yl) ethoxy)benzoate against Fusarium moniliforme and Sphaeropsis sapinea at a concentration of 200 μg/mL were 76.1% and 75.4%, respectively, which were better than that of carbendazim.

2023-10-01·Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society

Cheminformatics and biomolecular dynamics studies towards the discovery of anti-staphylococcal nuclease domain-containing 1 (SND1) inhibitors to treat metastatic breast cancer.

Article

作者: Makki Almansour, Nahlah

Metastatic breast cancer is a prime health concern and leading health burden across the globe. Previous efforts have shown that protein-protein interaction between Metadherin and Staphylococcal nuclease domaincontaining 1 (SND1) promotes initiation of breast cancer, progression, therapy resistance and metastasis. Therefore, small drug molecules that can interrupt the Metadherin and SND1 interaction may be ideal to suppress tumor growth, metastasis and increases chemotherapy sensitivity of triple negative breast cancer. Here, in this study, structure based virtual screening was conducted against the reported active site of SND1 enzyme, which revealed three promising lead molecules from Asinex library. These compounds were; BAS_00381028, BAS_00327287, and BAS_01293454 with binding energy score -10.25 kcal/mol, -9.65 kcal/mol and -9.32 kcal/mol, respectively. Compared to control (5-chloro-2-methoxy-N-([1,2,4]triazolo[1,5-a]pyridin-8-yl)benzene-1-sulfonamide) the lead molecules showed robust hydrophilic and hydrophobic interactions with the enzyme and revealed stable docked conformation in molecular dynamics simulation. During the simulation time, the compounds reported stable dynamics with no obvious fluctuation in binding mode and interactions noticed. The mean root mean square deviation (RMSD) of BAS_00381028, BAS_00327287, and BAS_01293454 complexes were 1.87 Å, 1.75 Å, 1.34 Å, respectively. Furthermore, the MM/GBSA analysis was conduction on the simulation trajectories of complexes that unveiled binding energy score of -19.25 kcal/mol, -27.03 kcal/mol, -34.6 kcal/mol and -29.61 kcal/mol for control, BAS_00381028, BAS_00327287, and BAS_01293454, respectively. In MM/PBSA, the binding energy value of for control, BAS_00381028, BAS_00327287, and BAS_01293454 was -20.45 kcal/mol, -27.89 kcal/mol, -36.41 kcal/mol and -32.01 kcal/mol, respectively. Additionally, the compounds were classified as druglike and have favorable pharmacokinetic properties. The compounds were predicted as promising leads and might be used in experimental investigation to study their anti-SND1 activity.

2022-12-31·Designed monomers and polymers

Improvement of two Mn²⁺ coordination polymers on cognitive function of aged rats after anesthesia

Article

作者: Zhang, Hui ; Jia, Qiang ; Zhang, Hao-Lin ; Tian, Fen

Two Mn²⁺ coordination polymers (CPs) with the scientific terms of {[Mn(TTPA)·(H₂O)₂]·H₂O} _n (1) and {[Mn(TTPA)·(H₂TTPA)]·2DMSO} _n (2) were favorably created on the basis of multidentate linking organic ligand 2,5-bis-(1,2,4-triazol-1-yl)-terephthalic acid (H₂TTPA) in the conditions of solvent-presupposed thermal reaction. To measure the influence of two Mn²⁺ coordination polymers with novel structures, the ELISA assay and real-time RT-PCR assay were conducted in this present research. First of all, the ELISA assay was conducted to measure the content of inflammatory cytokines released into the hippocampal tissue. In addition to this, the relative expression of the TAU protein in the brain was further determined with real-time RT-PCR assay.

项与 PBF-999 相关的新闻（医药）

2024-02-22

·Pharmaceutical Technology

Harmony wins orphan drug tag for pitolisant to treat Prader-Willi syndrome

Harmony reported Wakix (pitolisant) sales of $582m for full-year 2023, according to its annual report. Credit: rafapress via Shutterstock. US-based biopharmaceutical company Harmony Biosciences has secured a US Food and Drug Administration (FDA) orphan drug designation for its drug pitolisant, an investigational treatment for Prader-Willi Syndrome (PWS). Harmony now plans to advance the candidate into a Phase III clinical trial. The planned registrational TEMPO study will assess the safety and efficacy of pitolisant in treating excessive daytime sleepiness (EDS) and behavioural disturbances seen in PWS. Harmony has announced that it aims to initiate the global study in Q1 2024, enrolling patients six years and older with PWS. Commercialised as Wakix in the US, pitolisant is approved by the Food and Drug Administration for the treatment of Ehlers-Danlos syndrome (EDS) or cataplexy, a sudden muscle weakness that occurs while a person is awake, in adult patients with narcolepsy. The selective histamine 3 (H3) receptor antagonist/inverse agonist was initially developed by France-based Bioprojet, which granted an exclusive licence to Harmony for the development, manufacturing, and commercialisation of pitolisant in the US in 2017. Harmony reported Wakix sales of $582m for 2023, in its annual report. According to GlobalData’s Pharma Intelligence Center, pitolisant will generate nearly $2bn in sales in 2029, potentially being driven by an increase in demand following a possible approval for PWS. See Also: Immune-Onc’s antibody therapy collects second FDA orphan designation Ono Pharmaceutical partners with EME for antibody drug discovery GlobalData is the parent company of Pharmaceutical Technology. The orphan drug designation follows the announcement of preliminary positive Phase II (NCT04257929) data in 2022, where the trial met its primary endpoint of evaluating the variation on the Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD) to judge the therapy’s impact on EDS. PWS is a complex genetic condition that affects many parts of the body. It’s characterised by weak muscle tone, feeding difficulties, delayed development, and other issues. One of the most prominent features is an insatiable appetite, which can lead to chronic overeating and obesity if not managed carefully. In the announcement accompanying the orphan drug designation, Harmony’s chief medical officer Kumar Budur said: “We are excited about our upcoming Phase III TEMPO study and the progress we have made to broaden the clinical utility of pitolisant not just in Prader-Willi Syndrome but other rare diseases as part of our life cycle management programmes that, if successful, could potentially help over 100,000 patients.” Last May, Spanish biopharmaceutical company Palobiofarma teamed up with the Foundation for Prader Willi Research (FPWR) to develop its PWS drug PBF-999. The candidate is currently being investigated in a Phase II clinical trial.

临床2期孤儿药引进/卖出临床结果上市批准

2023-05-05

·Pharmaceutical Technology

Palobiofarma and FPWR partner to develop Prader Willi syndrome therapy

Palobiofarma’s PBF-999 has been developed to treat solid tumours such as colon cancer. Credit: Nemeziya / Shutterstock.com. Spanish biopharmaceutical company Palobiofarma has collaborated with the Foundation for Prader Willi Research (FPWR) to develop its PBF-999 to treat Prader Willi syndrome (PWS). The company has received a new venture philanthropy award as a convertible loan from FPWR. Recommended Reports Reports Von Willebrand Factor (VWF) Drugs in Development by Therapy Areas and Indications, Stages, MoA, R... GlobalData Reports LOA and PTSR Model - Ocrelizumab in Relapsing Remitting Multiple Sclerosis (RRMS) GlobalData View all It intends to utilise the funding from FPWR to partially fund its ongoing Phase II clinical trial of PBF-999, a dual adenosine A2a receptor antagonist/phosphodiesterase 10 (PDE-10) inhibitor. The PDE-10 inhibitor has been developed to treat ‘cold tumours,’ such as colon cancers. It has already been assessed in three clinical trials. Following observations of an appetite-reducing effect using PBF-999, Palobiofarma designed a clinical trial to assess its efficacy and safety in reducing hyperphagia (excessive hunger) in PWS adults. Palobiofarma CEO Dr Julio Castro stated: “We are excited to receive this funding from FPWR, which will enable us to continue our mission of developing a treatment to help patients with PWS.” Led by Dr Assumpta Caixàs, the clinical trial is being conducted at the university hospital Parc Taulí in Sabadell, Spain. FPWR executive director Susan Hedstrom stated: “Effective treatments for PWS hyperphagia are sorely needed and we are pleased to support Palobiofarma’s efforts on this front.” In 2018, Palobiofarma commenced recruitment of participants for a Phase I clinical trial of PBF-999 in patients with solid tumours. Conducted at the Vall D Hebron hospital in Barcelona, Spain, the trial was designed to assess the tolerability and safety of PBF-999.

临床1期临床2期

2023-04-27

·BioSpace

Palobiofarma Receives Venture Philanthropy Award from Foundation for Prader-Willi Research to Advance PBF-999 Development for Prader-Willi Syndrome Treatmenta

[Pamplona, Covina] - The Foundation for Prader Willi Research (FPWR) has provided a new venture philanthropy award, in the form of a convertible loan, to Palobiofarma S.L., a Spanish biopharmaceutical company focused on developing innovative treatments for serious diseases. Palobiofarma has a robust pipeline of promising drug candidates that are currently undergoing clinical development for a range of diseases, including cancer, respiratory, and metabolic disorders supported by an experienced team. FPWR’s philanthropic investment will be used to partially fund Palobiofarma's ongoing Phase 2 clinical trial to develop PBF-999 for the treatment of Prader Willi syndrome (PWS). PBF-999 is a phosphodiesterase 10 inhibitor that has been evaluated in three previous clinical studies. Observations of an appetite-reducing effect have led Palobiofarma to design a clinical study to test this compound in adults with PWS to evaluate safety and efficacy in the reduction of hyperphagia (excessive hunger). The clinical study is being conducted in the University Hospital Parc Taulí in Sabadell, Spain under the leadership of Dra. Assumpta Caixàs. "We are excited to receive this funding from FPWR, which will enable us to continue our mission of developing a treatment to help patients with PWS," said Dr. Julio Castro, CEO of Palobiofarma. "Effective treatments for PWS hyperphagia are sorely needed and we are pleased to support Palobiofarma’s efforts on this front," said Susan Hedstrom, Executive Director of the Foundation for Prader-Willi Research. The Foundation for Prader-Willi Research is a 501(c)(3) non-profit organization dedicated to eliminating the challenges of Prader-Willi syndrome through the advancement of research and therapeutic development. By providing funding and resources to companies like Palobiofarma, FPWR is helping to develop new treatments for people with PWS.

临床2期

100 项与 PBF-999 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
普拉德-威利综合症	临床2期	西班牙	Palobiofarma SL	2023-04-28
晚期恶性实体瘤	临床1期	西班牙	Palobiofarma SL	2017-10-01
亨廷顿舞蹈病	临床1期	西班牙	Palobiofarma SL	2014-09-01