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- ||| KAND567 / Kancera
Enrollment closed, Phase classification, Enrollment change, Trial completion date, Trial primary completion date: KANDOVA: A Study to Evaluate the Safety of KAND567, in Combination with Carboplatin Therapy, in Women with Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (clinicaltrials.gov) - Dec 18, 2024
P1/2, N=18, Active, not recruiting, Sponsor: Kancera AB
Recruiting --> Active, not recruiting | Phase classification: P2 --> P1/2 | N=30 --> 18 | Trial completion date: Jun 2024 --> Mar 2025 | Trial primary completion date: Jun 2024 --> Mar 2025
- | KAND567 / Kancera
Journal: T follicular helper cell is essential for M2 macrophage polarization and pulmonary vascular remodeling in hypoxia-induced pulmonary hypertension. (Pubmed Central) - Dec 5, 2024
This involved M2 macrophage polarization, PASMCs proliferation and pyroptosis. These data suggested that TFH/IL-21 axis may be a novel therapeutic target for the treatment of HPH.
- | KAND567 / Kancera
Journal: A Small Molecule Antagonist of CX3CR1 (KAND567) Inhibited the Tumor Growth-Promoting Effect of Monocytes in Chronic Lymphocytic Leukemia (CLL). (Pubmed Central) - Nov 27, 2024
Our data suggest that the CX3CR1/CX3CL1 axis is activated in CLL and may contribute to the NLC-driven growth-promoting effects of CLL cells. KAND567, which is in clinical trials in other disorders, should also be explored in CLL.
- | Journal: Dual Targeting of CX3CR1 and PARP in Models of High-Grade Serous Ovarian Carcinoma. (Pubmed Central) - Nov 27, 2024
KAND567, which is in clinical trials in other disorders, should also be explored in CLL. While the exact mechanisms determining the nature of the PARPis and AZD8797 interaction remain to be uncovered, our data indicate that, in a subset of models, selected PARPis strongly synergize with the inhibition of CX3CR1, suggesting a potential therapeutic opportunity.
- KAND567 / Kancera
Periadventitial Delivery of Nanoparticle-Encapsulated AZD8797 Reduces Venous Stenosis in a Murine Arteriovenous Fistula Model (Room 8, Convention Center) - Oct 12, 2024 - Abstract #KIDNEYWEEK2024KIDNEY_WEEK_4798;
Peri-adventitial delivery of AZD8797 NPs significantly reduces VNH/VS with improved vascular remodeling. This approach shows promise as a therapeutic strategy to enhance AVF patency.
- | KAND567 / Kancera
Journal: CX3CR1 deficiency promotes resolution of hepatic ischemia-reperfusion injury by regulating homeostatic function of liver infiltrating macrophages. (Pubmed Central) - May 21, 2024
CX3CR1 antagonist AZD8797 was injected i.p. to interrogate potential pharmacological therapeutic strategies...We observed that deficiency or pharmacological inhibition of CX3CR1 facilitated HIRI resolution via promoted macrophages migration in CCR1/CCR5 manner, as well as enhanced MerTK-mediated efferocytosis. Our study demonstrated the critical roles of CX3CR1 in progression of HIRI and identified it as a potential therapeutic target in clinical liver transplantation.
- KAND567 / Kancera
A CX3CR1 (FRACTALKINE RECEPTOR) SMALL MOLECULE ANTAGONIST (KAND567) SUPPRESSED THE GROWTH-PROMOTING EFFECT OF NURSE-LIKE CELLS IN CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) (Poster Area (Hall 7)) - May 15, 2024 - Abstract #EHA2024EHA_1624;
The CX3CR1 antagonist KAND567 inhibited NLC and NLC-mediatedgrowth-supportive effects on CLL cells in various read-out systems. The effect was specific for CLL monocytescompared to healthy monocytes.
- KAND567 / Kancera
Inhibition of fractalkine signalling in patients with acute myocardial infarction - First results from the FRACTAL trial (Science Box 1 - Research Gateway) - May 14, 2024 - Abstract #ESC2024ESC_5964;
Our pre-clinical studies also found an improvement in infarct size, inflammation and intramyocardial haemorrhage (IMH) when rats were pre-treated with the fractalkine inhibitor KAND567...Conclusion This first in-man study demonstrates that inhibition of the fractalkine pathway in STEMI patients appears safe and well-tolerated, while demonstrating a promising potential in preventing LV thrombus and IMH. The results suggest a new mechanism and class of drug to target reperfusion injury, clearly warranting a larger phase III study.
- KAND567 / Kancera
Fractalkine Inhibition in Acute Myocardial Infarction leads to reduced intramyocardial haemorrhage (Station 9 - Research Gateway) - May 14, 2024 - Abstract #ESC2024ESC_4436;
This seemed to be related to the smaller distribution IMH+, as the IMH+ infarcts were much larger in both arms, whilst overall infarct size in IMH subgroup were identical. Conclusion KAND567 appears to prevent the transition from IMH- to IMH+, while it doesn
- || KAND145 / Kancera
Trial completion, Enrollment change, Trial completion date, Trial primary completion date: Evaluation of Safety, Tolerability, Pharmacokinetics, Food Effect and Interaction With Midazolam in Healthy Volunteers After Oral Single and Multiple Ascending Dosing of KAND145 (clinicaltrials.gov) - Apr 22, 2024
P1, N=50, Completed, Sponsor: Kancera AB
Conclusion KAND567 appears to prevent the transition from IMH- to IMH+, while it doesn Recruiting --> Completed | N=88 --> 50 | Trial completion date: Sep 2024 --> Apr 2024 | Trial primary completion date: Sep 2024 --> Apr 2024
- || KAND567 / Kancera
Review, Journal: Chemokine Fractalkine and Non-Obstructive Coronary Artery Disease-Is There a Link? (Pubmed Central) - Apr 17, 2024
Whereas the link between FKN/CX3CL1 and NO-CAD appears evident, further studies are necessary to unveil this complex relationship. In this review, we critically overview the current data on FKN/CX3CL1 in the context of NO-CAD and present the novel clinical implications of the unique structure and function of FKN/CX3CL1 as a compound which distinctively contributes to the pathomechanism of this condition.
- | MK-2206 / Merck (MSD), KAND757 / Kancera
Journal: PFKFB3 facilitates cell proliferation and migration in anaplastic thyroid carcinoma via the WNT/?-catenin signaling pathway. (Pubmed Central) - Feb 21, 2024
In this review, we critically overview the current data on FKN/CX3CL1 in the context of NO-CAD and present the novel clinical implications of the unique structure and function of FKN/CX3CL1 as a compound which distinctively contributes to the pathomechanism of this condition. PFKFB3 can enhance ATC cell proliferation and migration via the WNT/?-catenin signaling pathway and plays a crucial role in the regulation of aerobic glycolysis in ATC cells.
- | KAND567 / Kancera
Preclinical, Journal: CX3CR1 mediates Motor Dysfunction in Mice through 5-HTR2a. (Pubmed Central) - Jan 30, 2024
While inhibiting the function of CX3CR1 by AZD8797 could decrease the expression of 5-Hydroxytryptamine receptor(5-HTR2a), which involved in the regulation of motor function...For the first time, we reported that neuronal CXCR1 mediates motor dysfunction. Our results suggest that modulating CXCR1 activity offers a novel therapeutic strategy for motor dysfunction.
- | KAND567 / Kancera
Journal: CX3CL1/CX3CR1 Signaling Mediated Neuroglia Activation Is Implicated in the Retinal Degeneration: A Potential Therapeutic Target to Prevent Photoreceptor Death. (Pubmed Central) - Jan 17, 2024
AZD8797, a CX3CR1 antagonist, was injected into the vitreous cavity of an RD model to modulate the neuroglia activation...Targeting the CX3CL1/CX3CR1 signaling may serve as an effective therapeutic strategy. Future refinements of these findings may cast light into the discovery of new medications for RD.
- | KAND567 / Kancera
Journal: SARS-CoV-2 Causes Brain Damage: Therapeutic Intervention with AZD8797. (Pubmed Central) - Dec 25, 2023
Histopathological analyses supported the protective effects of AZD8797 against SARS-CoV-2-induced damage. The CX3CL1-CX3CR1 signaling pathway could offer a promising target for reducing SARS-CoV-2's neurological impact, but additional research is needed to confirm these findings in combination with other therapies and assess the clinical significance.
- | KAND757 / Kancera
Journal: KAN0438757, a novel PFKFB3 inhibitor, prevent the progression of severe acute pancreatitis via the Nrf2/HO-1 pathway in infiltrated macrophage. (Pubmed Central) - Dec 22, 2023
And more importantly, KAN0438757 displayed negligible toxicity in vivo. Taken together our data suggest KAN0438757 directly suppresses the inflammatory role of PFKFB3 and induces a protective role via the Nrf2/HO-1 pathway, which could prove as an excellent therapeutic platform for SAP amelioration.
- || KAND145 / Kancera
Trial completion date, Trial primary completion date: Evaluation of Safety, Tolerability, Pharmacokinetics, Food Effect and Interaction With Midazolam in Healthy Volunteers After Oral Single and Multiple Ascending Dosing of KAND145 (clinicaltrials.gov) - Nov 28, 2023
P1, N=88, Recruiting, Sponsor: Kancera AB
- ||| KAND145 / Kancera
Enrollment open: Evaluation of Safety, Tolerability, Pharmacokinetics, Food Effect and Interaction With Midazolam in Healthy Volunteers After Oral Single and Multiple Ascending Dosing of KAND145 (clinicaltrials.gov) - Nov 13, 2023
P1, N=88, Recruiting, Sponsor: Kancera AB
Taken together our data suggest KAN0438757 directly suppresses the inflammatory role of PFKFB3 and induces a protective role via the Nrf2/HO-1 pathway, which could prove as an excellent therapeutic platform for SAP amelioration. Not yet recruiting --> Recruiting
- || KAND567 / Kancera
New P2 trial: KANDOVA: A Study to Evaluate the Safety of KAND567, in Combination with Carboplatin Therapy, in Women with Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (clinicaltrials.gov) - Oct 16, 2023
P2, N=30, Recruiting, Sponsor: Kancera AB
- ||| KAND145 / Kancera
New P1 trial: Evaluation of Safety, Tolerability, Pharmacokinetics, Food Effect and Interaction With Midazolam in Healthy Volunteers After Oral Single and Multiple Ascending Dosing of KAND145 (clinicaltrials.gov) - Oct 2, 2023
P1, N=88, Not yet recruiting, Sponsor: Kancera AB
- | KAND567 / Kancera
Journal: CX3CR1 regulates the development of renal interstitial fibrosis through macrophage polarization. (Pubmed Central) - Sep 23, 2023
Inhibiting CX3CR1 can effectively prevent the progression of renal interstitial fibrosis. The mechanism may be related to macrophage polarization towards M2 type and upregulation of Arg-1 expression.
- || KAND567 / Kancera
New P1 trial: Safety, Tolerability and Pharmacokinetics After Continuous Infusion of KAND567 (clinicaltrials.gov) - Sep 11, 2023
P1, N=23, Completed, Sponsor: Kancera AB
- | KAND567 / Kancera, dorsomorphin (Compound C) / EMD Serono
Journal: Fractalkine Enhances Hematoma Resolution and Improves Neurological Function via CX3CR1/AMPK/PPAR? Pathway After GMH. (Pubmed Central) - Aug 31, 2023
signaling pathway, which promoted M1/M2 microglial polarization. Activating CX3CR1 by r-FKN may provide a promising therapeutic approach for treating patients with GMH.
- | KAND567 / Kancera
New P2 trial: KAND567 Versus Placebo in Subjects Hospitalized With COVID-19 (clinicaltrials.gov) - Aug 25, 2023
P2, N=35, Terminated, Sponsor: Kancera AB
- | KAND567 / Kancera
Journal: Synergy of 5-aminolevulinate supplement and CX3CR1 suppression promotes liver regeneration via elevated IGF-1 signaling. (Pubmed Central) - Aug 14, 2023
Thus, short-term treatments with both 5-ALA and AZD8797 demonstrated pro-regeneration outcomes superior to 5-ALA-only treatments in mice after PHx. Overall, our findings may inspire safe and effective strategies to better treat PLT and PHx patients.
- || KAND567 / Kancera
Review, Journal: Fractalkine Signalling (CXCL1/CXCR1 Axis) as an Emerging Target in Coronary Artery Disease. (Pubmed Central) - Jul 29, 2023
Moreover, inhibition of CXCR1 with an allosteric small molecule antagonist (KAND567) in the rat MI model reduces acute infarct size, inflammation, and IMH. Here we review the cellular biology of fractalkine and its receptor, along with ongoing studies that introduce CXCR1 as a future target in coronary artery disease, specifically in patients with myocardial infarction.
- KAND757 / Kancera
In vitro and in vivo characterization of the novel PFKFB3 inhibitor KAN0438757 in colorectal cancer (Room A2) - Nov 30, 2022 - Abstract #DKK2022DKK_1741;
KAN0438757 showed a clear antiproliferative effect in rectal cancer cells and PDX without being overly toxic in vivo. It showed promis- ing synergistic efficacy when used in combination with chemotherapy and therefore should be further tested in vivo.
- | KAND757 / Kancera
Journal: Specific PFKFB3 Inhibitor Memorably Ameliorates Intervertebral Disc Degeneration via Inhibiting NF-κB and MAPK Signaling Pathway and Reprogramming of Energy Metabolism of Nucleus Pulposus Cells. (Pubmed Central) - Oct 4, 2022
KAN0438757 (KAN) is an effective inhibitor of selective metabolic kinase phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3) that has both energy metabolism reprogramming and anti-inflammatory effects...For the therapeutic aspect, the rat tail disc puncture model demonstrated that KAN has a significant ameliorated effect on the progression of IVDD. To sum up, our research successfully authenticated the potential therapeutic effect of KAN on IVDD and declaimed its mechanisms of both novel energy metabolism reprogramming and conventional anti-inflammation effect.
- | KAND567 / Kancera
Journal: Chondrocyte apoptosis in temporomandibular joint osteoarthritis promotes bone resorption by enhancing chemotaxis of osteoclast precursors. (Pubmed Central) - Jul 23, 2022
To sum up, our research successfully authenticated the potential therapeutic effect of KAN on IVDD and declaimed its mechanisms of both novel energy metabolism reprogramming and conventional anti-inflammation effect. This study indicates that apoptosis of chondrocytes in TMJOA enhances chemotaxis of OCPs toward osteoclast precursors through upregulation of the p38-CX3CL1 axis, thereby promoting the activation of local osteoclasts.
- | KAND567 / Kancera
Journal: Neuron derived fractalkine promotes microglia to absorb hematoma via CD163/HO-1 after intracerebral hemorrhage. (Pubmed Central) - Apr 14, 2022
This study indicates that apoptosis of chondrocytes in TMJOA enhances chemotaxis of OCPs toward osteoclast precursors through upregulation of the p38-CX3CL1 axis, thereby promoting the activation of local osteoclasts. We systematically identified that FKN may be a potential therapeutic target to improve hematoma absorption and we shed light on ICH treatment.
- | KAND567 / Kancera
Preclinical, Journal: FKN/CX3CR1 axis facilitates migraine-Like behaviour by activating thalamic-cortical network microglia in status epilepticus model rats. (Pubmed Central) - Apr 13, 2022
Our results indicated that epilepsy facilitated migraine through FKN/CX3CR1 axis-mediated microglial activation in the cortex/thalamus/sp5c, which was accompanied by BDNF release. Blocking the FKN/CX3CR1 axis and microglial activation are potential therapeutic strategies for preventing and treating migraine in patients with epilepsy.
- | KAND567 / Kancera
Preclinical, Journal: Antagonizing the CX3CR1 Receptor Markedly Reduces Development of Cardiac Hypertrophy After Transverse Aortic Constriction in Mice. (Pubmed Central) - Feb 19, 2022
Furthermore, AZD8797 treatment reduced the expression of the hypertrophic marker genes Nppa and Nppb as well as the profibrotic genes Tgfb1 and Col1a1 at 14 days after transverse aortic constriction. These findings strongly suggest the involvement of the CX3CR1/CX3CL1 pathway in the pathogenesis of left-ventricular hypertrophy.
- KAND567 / Kancera
Schizophrenic individuals hiPSC-derived astrocytes impair synaptic engulfment by induced microglial-like cells (iMGs) in vitro (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_559;
In order to verify whether SCZ astrocytic secreted CX3CL1 stimulates higher synaptic engulfment by microglia, HC induced microglial-like cells (iMGs) were incubated with astrocyte conditioned media (ACM) from both phenotypes, under non-stimulated (N.S.) or TNF-α stimulated conditions and in the presence or absence of the CX3CR1 antagonist (AZD 8797) for up to 24 h with CM-Dil-labeled synaptoneurosomes...Interestingly, TNF-α and IL-6 mRNA levels are elevated in stimulated SCZ astrocytes relative to HC astrocytes. Altogether, these results indicate that SCZ astrocytes secreted factors impair HC iMG synaptic engulfment.; Grant Support: CNPq Grant 441719/2020-1; FAPEMIG Grant APQ-00059-21; FAPEMIG Grant APQ-03744-17
- | Venclexta (venetoclax) / Roche, AbbVie, KAN0441571C / Kancera
Journal, IO biomarker: Predicting ROR1/BCL2 combination targeted therapy of small cell carcinoma of the lung. (Pubmed Central) - Oct 15, 2021
Synergy as defined by a combination index of <1 via the Chou-Talalay method between KAN0441571C and venetoclax was demonstrated in 8 SCLC cell lines. We have shown that ROR1 inhibition is synergistic with BCL2 inhibition in SCLC models and shows promise as a novel therapeutic target in SCLC.
- | KAND567 / Kancera
Journal: Targeting CX3CR1 Suppresses the Fanconi Anemia DNA Repair Pathway and Synergizes with Platinum. (Pubmed Central) - Apr 7, 2021
Importantly, CX3CR1i synergizes with platinum agents in a nonreversible manner in proliferation assays including platinum resistant models. Taken together, our results reveal an unanticipated interplay between CX3CR1 and the FA pathway and show for the first time that a clinical-phase small molecule inhibitor targeting CX3CR1 might show benefit in improving responses to DNA crosslinking chemotherapeutics.
- | KAND567 / Kancera
Preclinical, Journal: CX3CR1-microglia mediates neuroinflammation and blood pressure regulation in the nucleus tractus solitarii of fructose-induced hypertensive rats. (Pubmed Central) - Mar 23, 2021
We conclude that CX3CR1-microglia represses the nNOS signaling pathway and promotes chronic inflammation in fructose-induced hypertension. Collectively, our results reveal the role of chemokines such as IL-1β, IL-6, and TNF-α in NTS neuroinflammation with the involvement of FKN and CX3CR1.
- KAND567 / Kancera
[VIRTUAL] Pharmacological blockade of the CX3CR1/CX3CL1 fractalkine axis prevents alopecia areata in C3H/HeJ mice () - Feb 12, 2021 - Abstract #SID2021SID_699;
Furthermore, neutralizing CX3CL1 using an anti-CX3CL1 mAb significantly delayed AA development in C3H/HeJ skin grafted mice. Collectively, our data suggest that the CX3CR1/CX3CL1 axis contributes to the pathogenesis of AA, and introduces a novel therapeutic target for the treatment of AA.
- || KAND567 / Kancera
New P2 trial: KAND567 Versus Placebo in Subjects Hospitalized with COVID-19. A Phase II, Randomized, 2-Arm Parallel-Group, Double-blind Study to Evaluate Efficacy, Safety, Tolerability, and Pharmacokinetics. (EUDRACT) - Feb 7, 2021
P2, N=40, Ongoing, Sponsor: Kancera AB
- | KAND567 / Kancera
Preclinical, Journal: A novel CX3CR1 inhibitor AZD8797 facilitates early recovery of rat acute spinal cord injury by inhibiting inflammation and apoptosis. (Pubmed Central) - Feb 5, 2021
The effect of AZD8797 was mediated by suppressing apoptosis, necrosis and inflammatory responses, as assessed by WB/ELISA and morphological examinations. The current study has demonstrated that AZD8797 can effectively block overwhelming inflammation, apoptosis and necrosis after SCI and facilitate early recovery of locomotive function.
- Venclexta (venetoclax) / Roche, AbbVie, KAN0441571C / Kancera
[VIRTUAL] Predicting ROR1/BCL2 Combination Targeted Therapy of Small Cell Carcinoma of the Lung (ePoster Hall) - Dec 17, 2020 - Abstract #IASLCWCLC2020IASLC_WCLC_1103;
Synergy as defined by a combination index of <1 via the Chou-Talalay method between KAN0441571C and venetoclax was demonstrated in all 8 SCLC cell lines. Conclusion We have demonstrated that ROR1 inhibition is synergistic with BCL2 inhibition in SCLC models and shows promise as a novel therapeutic target in SCLC.
- Venclexta (venetoclax) / Roche, AbbVie, KAN0439834 / Kancera, Imbruvica (ibrutinib) / AbbVie, J&J
Diffuse Large B Cell Lymphoma (DLBCL) Expresses ROR1 and a ROR1 Small Molecule Inhibitor (KAN0441571C) Induced Significant Apoptosis of Tumor Cells (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_3735;
The molecule was more effective in inducing apoptosis of DCBCL cells than venetoclax or ibrutinib . New anti-cancer drugs with other mechanisms of action than those clinically available for DLBCL are warranted to improve the prognosis .
- | KAN0439834 / Kancera
Journal: First-in-class oral small molecule inhibitor of the tyrosine kinase ROR1 (KAN0439834) induced significant apoptosis of chronic lymphocytic leukemia cells. (Pubmed Central) - Jun 15, 2019
New anti-cancer drugs with other mechanisms of action than those clinically available for DLBCL are warranted to improve the prognosis . No abstract available