Delving into the Latest Updates on Vatalanib succinate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

PTK/ZK, Vatalanib, vatalanib-succinate

+ [7]

Target

PDGFR x VEGFR1 x VEGFR2 x VEGFR3 x c-Kit

Mechanism

PDGFR inhibitors(Platelet-derived growth factor receptor inhibitors), VEGFR1 antagonists(Vascular endothelial growth factor receptor 1 antagonists), VEGFR2 antagonists(Vascular endothelial growth factor receptor 2 antagonists)

Therapeutic Areas

NeoplasmsDigestive System DisordersImmune System Diseases+ [11]

Active Indication-

Inactive Indication

Advanced breast cancerAdvanced cancerAdvanced Malignant Solid Neoplasm+ [54]

Originator Organization

Novartis Pharma AG

Active Organization-

Inactive Organization

Novartis AG

Dana-Farber Cancer Institute, Inc.

Novartis Pharmaceuticals Corp.

+ [3]

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

Structure

Molecular FormulaC24H21ClN4O4

InChIKeyLLDWLPRYLVPDTG-UHFFFAOYSA-N

CAS Registry212142-18-2

RATIONALE: Vatalanib and pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Vatalanib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving vatalanib together with pemetrexed disodium may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of vatalanib when given together with pemetrexed disodium in treating patients with advanced solid tumors.

Start Date25 Jan 2007

Sponsor / Collaborator

Mayo Clinic

[+1]

NCT00615160 / TerminatedPhase 1/2IIT

Phase II Randomized, Parallel-Group Trial on PTK-ZK With or Without DTIC in Patients With Non-resectable Metastatic Malignant Melanoma

To evaluate the efficacy of PTK-ZK on metastatic melanoma either as a single agent treatment or in combination with standard chemotherapy according to RECIST criteria. Further to evaluate the safety and tolerability of PTK-ZK in patients with metastatic melanoma either as a single agent treatment or in combination with standard chemotherapy

Start Date01 Dec 2006

Sponsor / Collaborator-

100 Clinical Results associated with Vatalanib succinate

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100 Translational Medicine associated with Vatalanib succinate

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100 Patents (Medical) associated with Vatalanib succinate

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534

Literatures (Medical) associated with Vatalanib succinate

01 Mar 2024·Bioactive materials

Reactive oxygen species (ROS)-mediated M1 macrophage-dependent nanomedicine remodels inflammatory microenvironment for osteoarthritis recession

Article

Author: Yi, Nanxing ; Wang, Kaiqiang ; Liang, Qianqian ; Zhang, Weian ; Tian, Jia ; Xu, Hao ; Li, Xiaofeng ; Sun, Dawei ; Xiong, Mengting ; Liu, Yang ; Wang, Yongjun ; Xue, Chunchun ; Cui, Zepeng

Osteoarthritis (OA) is a common chronic inflammatory disorder. Effective remodeling of inflammatory microenvironment in the joint is a promising strategy to prevent OA. However, current drugs remain unsatisfactory due to a lack of targeted and effective ways for relieving inflammatory conditions in OA joints. Bortezomib (BTZ), a proteasome inhibitor, could effectively inhibit proinflammatory cytokines but with poor accumulation in the inflammatory tissues. To overcome the shortcomings of BTZ delivery and to improve the efficacy of OA therapy, herein, we designed a novel nanomedicine (denoted as BTZ@PTK) by the co-assembly of BTZ and an amphiphilic copolymer (denoted as PTK) with ROS-cleaved thioketal (TK) linkages. The TK units in BTZ@PTK are first cleaved by the excessive ROS at OA sites, and then triggered the controlled release of BTZ, resulting in the accurate delivery and the inflammatory microenvironment remodeling. Accordingly, BTZ@PTK suppressed ROS generation and proinflammatory cytokines while promoting M1 macrophage apoptosis in lipopolysaccharide (LPS)-activated RAW264.7 macrophages or LPS/IFN-γ-treated primary macrophages, which leads to a better effect than BTZ. In OA mice, BTZ@PTK passively accumulates into inflamed joints to attenuate pain sensitivity and gait abnormality. Importantly, BTZ@PTK treatment successfully ameliorates synovitis with the reduction of synovial hyperplasia and synovitis scores by suppressing M1 macrophage polarization and promoting M1 macrophage apoptosis in the synovium, thereby delaying cartilage damage. Collectively, BTZ@PTK can effectively modulate inflammatory microenvironment for OA recession by activating M1 macrophage apoptosis and inhibiting M1macrophage-mediated inflammatory response.

01 Feb 2024·Archives of toxicology

Analysis of vascular disruption in zebrafish embryos as an endpoint to predict developmental toxicity

Article

Author: Tal, Tamara ; Nöth, Julia ; Ambekar, Akhil ; Scholz, Stefan ; Lai, Chih ; Kießling, Tobias R ; Busch, Wibke

Abstract:

Inhibition of angiogenesis is an important mode of action for the teratogenic effect of chemicals and drugs. There is a gap in the availability of simple, experimental screening models for the detection of angiogenesis inhibition. The zebrafish embryo represents an alternative test system which offers the complexity of developmental differentiation of an entire organism while allowing for small-scale and high-throughput screening. Here we present a novel automated imaging-based method to detect the inhibition of angiogenesis in early life stage zebrafish. Video subtraction was used to identify the location and number of functional intersegmental vessels according to the detection of moving blood cells. By exposing embryos to multiple tyrosine kinase inhibitors including SU4312, SU5416, Sorafenib, or PTK787, we confirmed that this method can detect concentration-dependent inhibition of angiogenesis. Parallel assessment of arterial and venal aorta ruled out a potential bias by impaired heart or blood cell development. In contrast, the histone deacetylase inhibitor valproic acid did not affect ISV formation supporting the specificity of the angiogenic effects. The new test method showed higher sensitivity, i.e. lower effect concentrations, relative to a fluorescent reporter gene strain (Tg(KDR:EGFP)) exposed to the same tyrosine kinase inhibitors indicating that functional effects due to altered tubulogenesis or blood transport can be detected before structural changes of the endothelium are visible by fluorescence imaging. Comparison of exposure windows indicated higher specificity for angiogenesis when exposure started at later embryonic stages (24 h post-fertilization). One of the test compounds was showing particularly high specificity for angiogenesis effects (SU4312) and was, therefore, suggested as a model compound for the identification of molecular markers of angiogenic disruption. Our findings establish video imaging in wild-type strains as viable, non-invasive, high-throughput method for the detection of chemical-induced angiogenic disruption in zebrafish embryos.

01 Oct 2023·Journal of ethnopharmacology

Xinkeshu tablets promote angiogenesis in zebrafish embryos and human umbilical vein endothelial cells through multiple signaling pathways

Article

Author: Zhang, Yun ; He, Qiuxia ; Zhang, Huazheng ; Xia, Qing ; Liu, Kechun ; Zhou, Honglei ; Liu, Qing ; An, Ying

ETHNOPHARMACOLOGICAL RELEVANCE:

Angiogenesis is particularly important in ischemic cardiovascular diseases such as coronary heart disease (CHD). Xinkeshu tablets (XKS) are a commonly used Chinese patent medicine for CHD with a defined clinical effect. However, the proangiogenic effect of XKS remains unknown.

AIM OF THE STUDY:

We attempted to investigate the chemical composition and proangiogenic effect of XKS, as well as its underlying mechanisms.

MATERIALS AND METHODS:

The chemical composition of a XKS methanol extract was analyzed using a UPLC-Q-Orbitrap-MS system. The compound's proangiogenic effects were evaluated in zebrafish embryos and human umbilical vein endothelial cells (HUVECs). Furthermore, the underlying mechanisms were investigated using transcriptome assays and real-time quantitative PCR validation.

RESULTS:

We identified 116 chemical constituents of XKS. XKS significantly stimulated subintestinal vessel plexus (SIVs) growth and rescued tyrosine kinase inhibitor (PTK787)-induced intersegmental vessels (ISVs) injury in zebrafish in a concentration-dependent manner. XKS significantly rescued the proliferation, migration capacity and tube formation of Recombinant VEGFR tyrosine kinase inhibitor II (VRI)-injured HUVECs. XKS promoted angiogenesis through multiple signaling pathways, including metabolic pathways, the PPAR signaling pathway, the AGE-RAGE signaling pathway, the NOD-like receptor signaling pathway, the VEGF signaling pathway, and the PI3K/Akt signaling pathway.

CONCLUSION:

Herein, we identified 116 chemical constituents of XKS for the first time and demonstrated that XKS may regulate angiogenesis through multiple signaling pathways to treat CHD.

2

News (Medical) associated with Vatalanib succinate

03 Aug 2023

·www.fiercebiotech.com

Agios looks beyond PK activators with $17.5M deal for Alnylam's siRNA blood disease program

TMPRSS6 is being developed for patients with polycythemia vera, a disease characterized by excessive production of red blood cells that can ultimately prove fatal. Agios Pharmaceuticals is basking in the “tremendous progress” of its PK activator pipeline, but that hasn’t stopped the biotech from looking for ways to freshen up its hematology portfolio courtesy of a preclinical siRNA program from Alnylam. Agios is paying $17.5 million upfront for the program with up to $130 million in development and regulatory milestones potentially to follow. In return, Agios is taking on sole responsibility for ushering the TMPRSS6 program through the clinic and, hopefully, to market, with Alnylam providing manufacturing support for phase 1 only. The program is being developed for patients with polycythemia vera, a disease characterized by excessive production of red blood cells that can ultimately prove fatal. Despite affecting around 100,000 patients in the U.S., according to Agios, there are no disease-modifying treatments available. The aim of the siRNA program is to target knockdown of TMPRSS6, which is a key driver of red blood cell production. So far, the program has demonstrated a 90% knockdown of TMPRSS6 mRNA over three months in nonhuman primates, which Agios said supports “the potential for an infrequent dosing regimen.” “This program is highly aligned with our core scientific expertise, clinical development and commercial capabilities in rare hematology as well as our business development strategy to expand beyond our industry-leading pipeline of PK activators,” Agios CEO Brian Goff said in the release. “We look forward to initiating IND-enabling studies this year with the aim of delivering a transformative treatment option for this patient community with profound unmet need.” Agios describes itself as the “pioneering leader in PK activation.” In the company’s second-quarter earnings release, which coincided with the licensing announcement, Goff pointed to positive phase 2 data from the biotech’s approved PTK inhibitor Pyrukynd in sickle cell disease last month. But rather than double down on the “tremendous progress executing across our industry-leading pipeline of PK activators,” Goff used the earnings release to announce that the company is “further expanding our portfolio beyond PK activation through focused business development.” The latest licensing deal also marks a good summer for Alnylam, which only last week pocketed $310 million from Roche in exchange for most of the rights to the midstage hypertension med zilebesiran.

License out/inPhase 2Phase 1

15 Jul 2023

·www.prnewswire.com

Leiomyosarcoma Pipeline Research Report 2023: Comprehensive Insights About 10+ Companies and 10+ Pipeline Drugs - Assessment by Product Type, Stage, RoA, and Molecule Type

DUBLIN, July 14, 2023 /PRNewswire/ -- The "Leiomyosarcoma - Pipeline Insight, 2023" clinical trials has been added to ResearchAndMarkets.com's offering. "Leiomyosarcoma - Pipeline Insight, 2023" report provides comprehensive insights about 10+ companies and 10+ pipeline drugs It covers the pipeline drug profiles, including clinical and nonclinical stage products. It also covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space. The companies and academics are working to assess challenges and seek opportunities that could influence Leiomyosarcoma R&D. The therapies under development are focused on novel approaches to treat/improve Leiomyosarcoma. Leiomyosarcoma Emerging Drugs Chapters This segment of the Leiomyosarcoma report encloses its detailed analysis of various drugs in different stages of clinical development, including phase II, I, preclinical and Discovery. It also helps to understand clinical trial details, expressive pharmacological action, agreements and collaborations, and the latest news and press releases. Leiomyosarcoma: Pipeline Development Activities The report provides insights into different therapeutic candidates in phase II, I, preclinical and discovery stage. It also analyses Leiomyosarcoma therapeutic drugs key players involved in developing key drugs. Pipeline Development Activities The report covers the detailed information of collaborations, acquisition and merger, licensing along with a thorough therapeutic assessment of emerging Leiomyosarcoma drugs. Leiomyosarcoma Emerging Drugs ADI PEG20: Polaris Group ADI-PEG 20 is a first-in-class therapeutic approach to deplete arginine and starve cancer cells. Because arginine is one of the 20 amino acids that are essential for protein synthesis and survival of cells, some cancer cells become dependent upon the external supply of arginine to survive and grow. ADI-PEG 20 is designed to deplete the external supply of arginine, which causes arginine-dependent cancer cells to die while leaving the patient's normal cells unharmed. Currently, it is in Phase III stage of clinical trial evaluation to treat Leiomyosarcoma. AL-3818: Advenchen Laboratories AL3818 is a novel small molecule PTK inhibitor being developed by Advenchen Laboratories. Advenchen Laboratories is conducting a Phase III study to evaluate the safety and efficacy of AL3818 (anlotinib) hydrochloride in the treatment of metastatic or advanced alveolar soft part sarcoma (ASPS), leiomyosarcoma (LMS), and synovial sarcoma (SS). Leiomyosarcoma: Therapeutic Assessment This segment of the report provides insights about the different Leiomyosarcoma drugs segregated based on following parameters that define the scope of the report, such as: Phases Late stage products (Phase III) Mid-stage products (Phase II) Early-stage product (Phase I) along with the details of Pre-clinical and Discovery stage candidates Discontinued & Inactive candidates Route of Administration Products have been categorized under various ROAs such as Oral Parenteral intravenous Subcutaneous Topical. Molecule Type Products have been categorized under various Molecule types such as Monoclonal Antibody Peptides Polymer Small molecule Gene therapy Product Type Leiomyosarcoma Report Assessment Pipeline Product Profiles Therapeutic Assessment Pipeline Assessment Inactive drugs assessment Unmet Needs Key Players Merck Advenchen Laboratories Trillium Therapeutics PTC Therapeutics PharmaMar Philogen EMD Serono Incyte Corporation Clovis Oncology, Inc. Key Products Avelumab AL3818 Pembrolizumab TTI-621 PTC596 ET-743 L19-hTNF M6620 Itacitinib Rucaparib For more information about this clinical trials report visit About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends. Media Contact: Research and Markets Laura Wood, Senior Manager [email protected] For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900 U.S. Fax: 646-607-1907 Fax (outside U.S.): +353-1-481-1716 Logo: SOURCE Research and Markets

Phase 3Phase 2Phase 1Gene Therapy

100 Deals associated with Vatalanib succinate

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic colon cancer	Phase 3	US	Novartis AG	01 Feb 2003
Metastatic colon cancer	Phase 3	AU	Novartis AG	01 Feb 2003
Metastatic colon cancer	Phase 3	BE	Novartis AG	01 Feb 2003
Metastatic colon cancer	Phase 3	BR	Novartis AG	01 Feb 2003
Metastatic colon cancer	Phase 3	CA	Novartis AG	01 Feb 2003
Metastatic colon cancer	Phase 3	CZ	Novartis AG	01 Feb 2003
Metastatic colon cancer	Phase 3	FR	Novartis AG	01 Feb 2003
Metastatic colon cancer	Phase 3	DE	Novartis AG	01 Feb 2003
Metastatic colon cancer	Phase 3	HU	Novartis AG	01 Feb 2003
Metastatic colon cancer	Phase 3	IT	Novartis AG	01 Feb 2003

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00348790 (CTgov)	Phase 2	Sarcoma \| Meningioma	25	vatalanib	srkpafbcop(ioqlhbahxq) = kdriciueiw vngvddujvb (dddakclnbb, myodzixffn - kcpldqsqgc) View more	-	27 Oct 2014
NCT00185588 (CTgov)	Phase 1/2	Pancreatic Cancer	33	gemcitabine+Vatalanib (Stage 1 Dose Exploration 0 - Gemcitabine 700 + Vatalanib 1250)	yvxsgbafee(gxnexwiogr) = mdddtxmfwr ccegjtmbhg (ifpjuyzsiw, prfvyqyauk - rhkfyfurmb) View more	-	15 Sep 2014
NCT00185588 (CTgov)	Phase 1/2	Pancreatic Cancer	33	gemcitabine+Vatalanib (Stage 1 Dose Exploration 1 - Gemcitabine 850 + Vatalanib 1250)	yvxsgbafee(gxnexwiogr) = azdejqpdtp ccegjtmbhg (ifpjuyzsiw, oytoqjhepx - lgljufjmxn) View more	-	15 Sep 2014
NCT00072475 (CTgov)	Phase 2	Myelodysplastic-Myeloproliferative Diseases \| Leukemia \| Myelodysplastic Syndromes	155	vatalanib	iztgejugna(rswsgsunzq) = aumyrfpvqd luovmfavon (uhuwuplkhy, bflbqsrdor - idnyszestg) View more	-	24 Jun 2014
NCT00072475 (Alliance, Pubmed \| Invest New Drugs)	Phase 2	Myelodysplastic Syndromes	155	Vatalanib 1250 mg	avjmhdndom(jildsejjqk) = possibly related to vatalanib yhprrotsjg (pjrgukyiwy ) View more	-	01 Oct 2013
NCT00072475 (Alliance, Pubmed \| Invest New Drugs)	Phase 2	Myelodysplastic Syndromes	155	Vatalanib 750-1250 mg		-	01 Oct 2013
NCT00053885 (CALGB 30107, Pubmed \| Lung Cancer)	Phase 2	Mesothelioma, Malignant	47	Vatalanib 1250 mg	fuhcelcumi(ezhdodeadv) = asqnujcuhp rbpmbyhiux (sdgeesmbka ) View more	Negative	01 Jun 2012
NCT00160043 (Pubmed \| Ann Oncol)	Phase 2	Non-Small Cell Lung Cancer Second line	112	Vatalanib once-daily dosing (QD)	jvojegvach(hpmgsnhhht) = qjfxqgcyrc rlmywuicvk (pqxitdkdpy ) View more	-	01 Mar 2012
NCT00160043 (Pubmed \| Ann Oncol)	Phase 2	Non-Small Cell Lung Cancer Second line	112	Vatalanib two divided daily dosing (TDD)	jvojegvach(hpmgsnhhht) = qmwntlnmbw rlmywuicvk (pqxitdkdpy ) View more	-	01 Mar 2012
ASCO2011	Phase 2	Recurrent Anaplastic (Malignant) Meningioma	21	PTK787/ZK 222584	atozycngph(dqrspyjsux) = qpthedwfqu xaxeerdrlv (ccxafhuggq )	-	20 May 2011
NCT00563823 (Pubmed \| Eur J Cancer)	Phase 2	Metastatic melanoma	-	Vatalanib	vcgczkgerq(ljddaajbqs) = fanjbhmkjy dxuloxrueo (vxujyqqeuf ) View more	Negative	01 Oct 2010
NCT00387933 (Pubmed \| Cancer)	Phase 1	Glioma	37	Vatalanib	hdxxdzinva(zrnoxyhaqy) = DLTs were hematologic, gastrointestinal, renal, and hepatic rsqmjdzgcg (tpufvvdqzd )	-	15 May 2009
ASCO2008	Phase 2	Metastatic melanoma	34	PTK787	azpxlqtwhd(couzzxsgdp) = asnipxawyu xntajiwrmr (hvktdboncr )	-	20 May 2008